Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
• Histological confirmed primary SCC of the vulva
• T1 tumor, not encroaching urethra/vagina/anus
• Depth of invasion > 1mm
• Tumor diameter < 4cm
• Unifocal tumor
• No enlarged (>1.5cm) or suspicious inguinofemoral lymph nodes at imaging
(CT/MRI/ultrasound)
• Possibility to obtain informed consent
• Metastatic sentinel lymph node; size of metastasis > 2mm and / or extracapsular
extension, or
• Metastatic sentinel lymph node: more than 1 SN with metastasis ≤ 2mm
• Patients are able to understand requirements of study, provide written informed
consent and comply with the study and follow-up procedures
• Adequate bone marrow, renal and liver function:
• Absolute neutrophil count ≥ 1.5 x 109 /L
• Platelet count ≥ 100 x 109 /L
• Creatinine clearance ≥ 40 ml/min measured by the Cockroft Gault formula
• Total bilirubin < 1.25 x ULN Aspartate transaminase (AST) and alanine
transaminase (ALT) ≤ 2.5 x ULN
• Performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Scale
(Appendix A)
• Age 18 years or older
• Life expectancy of ≥ 12 weeks
• Written informed consent
Exclusion Criteria:
• Inoperable tumors and tumors > 4cm
• Multifocal tumors
• Tumors with other pathology than squamous cell carcinoma
• Patients with enlarged / suspicious lymph nodes which are proven metastatic after fine
needle aspiration cytology
• No other carcinomas, other than basal cell carcinomas, within last 5 years
• History of pelvic radiotherapy
• History of any infection requiring hospitalization or antibiotics within 2 weeks
before enrollment
• Pregnant female or nursing mother
• Desire to become pregnant
• Known brain or spinal cord metastases unless adequately treated (surgery or
radiotherapy) with no evidence of progression and neurologically stable off
anticonvulsants and steroids
• Unstable angina, myocardial infarction, cerebrovascular accident, > Class II
congestive heart failure according to the New York Heart Association Classification
for Congestive Heart Failure (see Appendix B) within 6 months before enrollment
Radiation: Radiotherapy combined with cisplatin, Drug: Cisplatin
Study to Assess the Effect of Ofatumumab in Treatment Naïve, Very Early RRMS Patients Benchmarked Against Healthy Controls. (AGNOS)
This study will evaluate the impact of ofatumumab in Relapsing Remitting Multiple Sclerosis
(RRMS) participants that are very early in the course of their disease using clinical and
magnetic resonance imaging (MRI) outcomes. The study will also assess changes in disease
using monitoring techniques including digital biometric device use, biomarker analysis and
non-conventional MRI. Select outcomes in the ofatumumab treated group will be compared to a
group of Healthy participants to determine if there are similarities between the groups after
the patients with MS undergo treatment with ofatumumab.
Participants eligible for inclusion in this study must meet all of the following criteria:
1. Signed informed consent must be obtained prior to participation in the study
2. Age 18-35 years
Patients in the healthy control arm eligible for inclusion must fulfill the following
criteria:
3. Able to obtain MRI (HC with abnormal MRI at Screening will be excluded) and use
wearable device
4. Able to provide blood sample (no CSF will be collected in HC)
Patients in the ofatumumab-treated arm eligible for inclusion must fulfill the
following criteria:
5. Diagnosis of RRMS per McDonald Criteria (2010/2017)
6. Within 6 months of diagnosis of clinically definite MS (CDMS)
7. EDSS 0-3.0 (Inclusive)
8. Treatment-naïve to MS DMT
9. Able to obtain MRI and attend study visits at sites
10. Able to use wearable device
11. Able to provide blood sample (and CSF for sub-group n=15)
Key
Exclusion Criteria:
Participants in the healthy control arm meeting any of the following criteria are not
eligible for inclusion in this study:
1. Confounding medical condition as determined by the investigator
RRMS patients fulfilling any of the following exclusion criteria are not eligible for
inclusion in this study:
2. Diseases other than multiple sclerosis responsible for the clinical or MRI
presentation
3. Patients with neuromyelitis optica, Radiologic/ Clinically Isolated Syndrome,
Secondary Progressive or Primary Progressive MS diagnosis
4. Use of experimental or investigational drugs for MS
5. Previous use of Disease Modifying Therapy (DMT) or chemotherapeutic medications for MS
6. Relapse between screening and Baseline visits
7. Known sensitivity to gadolinium; patients with chronic, severe kidney disease
8. Known history of hypersensitivity to any of the study treatments or its excipients or
to drugs of similar chemical classes
9. CNS anomalies that are better accounted for by another disease process or MRI
anomalies causing clinically apparent impairments
10. Known active malignancies
11. Pregnant or nursing (lactating) women
12. Females of childbearing potential (all women physiologically capable of becoming
pregnant) should use effective contraception while receiving ofatumumab and for 6
months after the last treatment of ofatumumab
13. Patients with an active chronic disease (or stable but treated with immune therapy) of
the immune system other than MS or with immunodeficiency syndrome
14. Patients with active infections including systemic bacterial, viral (including
SARS-CoV-2/COVID-19) or fungal infections, or known to have AIDS or to test positive
for HIV antibody at Screening
15. Patients with neurological findings consistent with Progressive Multifocal
Leukoencephalopathy (PML), or confirmed PML
16. Patients with IgG or IgM levels below LLN at Screening
17. Patients that have received any live or live-attenuated vaccines within 4 weeks prior
to first dose of study drug administration
18. Patients at risk of developing or having reactivation of hepatitis
Drug: Ofatumumab
Brain and Nervous System, Relapse Remitting Multiple Sclerosis
early relapsing multiple sclerosis, ofatumumab, healthy control, treatment naïve, young adult population, MS-related disability, biomarker, MRI
Prospective Treatment Efficacy in IPF Using Genotype for Nac Selection (PRECISIONS) Trial (PRECISIONS)
The purpose of this study is to compare the effect of n-acetylcysteine (NAC) plus standard
care with matched placebo plus standard of care in patients diagnosed with idiopathic
pulmonary fibrosis (IPF) who have the TOLLIP rs3750920 TT genotype. The study will compare
the time to a composite endpoint of relative decline in lung function [10% relative decline
in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or
all-cause mortality]
The secondary objectives will be to examine the effect of NAC on the components of the
primary composite endpoint, the rates of clinical events, change in physiology, change in
health status, and change in respiratory symptoms.
• ≥ 40 years of age
• Diagnosed with IPF according to 2018 ATS/ERS/JRS/ALAT, confirmed by enrolling
investigator
• Signed informed consent
• If taking pirfenidone or nintedanib, must be on stable dose for at least 6 weeks prior
to enrollment visit
• Confirmed rs3570920 TT TOLLIP genotype
Exclusion Criteria:
• Pregnancy or planning to become pregnant
• Women of childbearing potential not willing to remain abstinent (refrain from
heterosexual intercourse) or use two adequate methods of contraception, including at
least one method with a failure rate of <1% per year during study participation
• Significant medical, surgical or psychiatric illness that in the opinion of the
investigator would affect subject safety, including liver and renal failure
• Receipt of an investigational drug or biological agent within the previous 4 weeks of
the screening visit or 5 times the half-life, if longer
• Supplemental or prescribed NAC therapy within 60 days of enrollment
• Listed for lung transplantation at the time of screening
• History of lung cancer
• Inability to perform spirometry
• Forced vital capacity (FVC) less than 45% predicted, using the global lung function
index (GLI) equation at Visit 1
• Active respiratory infection requiring treatment with antibiotics within 4 weeks of
Visit 1
Fractionated 1927nm Laser for Hyperpigmentation in Fitzpatrick Skin Phototypes V and VI
The primary objective of this study is to assess the efficacy of 1927nm non-ablative
fractionated laser therapy to treat hyperpigmentation in patients ages 18-75 with Fitzpatrick
Skin Phototypes V and VI and explore an effective, adjunctive pre- and post-procedural
regimen to prevent iatrogenic dyspigmentation or scarring in this population.
1. Healthy male, female, and non-binary adults between 18 and 75 years of age
2. Fitzpatrick Skin Phototype V and VI
3. Individuals deemed by the Investigator to have clinically significant
hyperpigmentation on their face and desire treatment and correction of this condition
4. Individuals willing to withhold aesthetic therapies (excluding those explicitly
prescribed by the Investigator as pre-treatment) for the duration of the study
5. Women of childbearing potential who agree to take a urine pregnancy test at the
Screening visit or when deemed by Investigator. Women of childbearing potential must
have a negative urine pregnancy test and must not be lactating at Screening. Women
must be willing and able to use an acceptable method of birth control (see below)
during the study. Women will not be considered of childbearing potential if one or
more of the following is documented:
• Postmenopausal for 12 months prior to initiation of the study
• Without a uterus +/- both ovaries prior to initiation of the study
• Bilateral tubal ligation 6 months prior to initiation of the study
6. Individuals of childbearing potential who use an acceptable method of contraception
for the duration of the study. Acceptable modes of birth control include the
following:
• Established use of hormonal contraception (oral, injectable, implanted, patch or
vaginal ring)
• Barrier methods with spermicide: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
• Intrauterine device (IUD) or intrauterine system (IUS)
• Surgical sterilization (e.g., vasectomy confirmed to be effective by sperm count
check, tubal occlusion, hysterectomy, bilateral salpingectomy/oophorectomy)
• Abstinence from heterosexual intercourse, when this is in line with the preferred
and usual lifestyle of the subject. Periodic abstinence (e.g., calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal methods are not
acceptable forms of contraception.
7. Individuals who can read, speak, write, and understand English and who are willing to
provide written informed consent.
8. Individuals willing to sign a photography release.
9. Individuals willing and able to cooperate with all study requirements for the duration
of the study, including prescribed pre- and post-procedure topical regimens
Exclusion Criteria:
1. Ages < 18 or > 75 years old
2. Fitzpatrick Skin Phototypes I-IV
3. Known history of allergies or irritant contact dermatitis in response to general skin
care products, including Hydroquinone and Retinol
4. Known allergies or irritant contact dermatitis in response to common ingredients of
physical sunscreen, including but not limited to Zinc Oxide
5. Known allergies or irritant contact dermatitis to topical anesthetics, including
Benzocaine and Tetracaine.
6. Active local or systemic disorders that may affect wound healing or integrity of the
integumentary system
7. History of active or inactive systemic granulomatous disease, (e.g., Sarcoidosis,
Tuberculosis, Granulomatosis with Polyangiitis, etc.), or connective tissue disorders
(e.g., Systemic Lupus Erythematosus, Dermatomyositis, Scleroderma, etc.)
8. Recent history of surgery or significant trauma to the area(s) to be treated
9. Significant scarring (excluding acne scars) in the area(s) to be treated
10. Current or history of hypertrophic scarring or keloid scars
11. Severe or cystic and clinically active acne on the area(s) to be treated
12. Tattoos in the area(s) to be treated
13. Individuals who currently have cancerous or pre-cancerous lesions in the area(s) to be
treated and/or have a history of skin cancer
14. Individuals with skin pathology and/or pre-existing dermatologic condition in the
treatment area (i.e., psoriasis, rosacea, eczema, seborrheic dermatitis, vitiligo,
hyper or hypo-skin pigmentation conditions such as post inflammatory
hyperpigmentation) that the Investigator deems inappropriate for participation or
could interfere with outcomes of the study.
15. History of chronic drug or alcohol use.
16. Microdermabrasion or glycolic acid treatment to the treatment area(s) within 4 weeks
of study participation or who plan on having this treatment during the study.
17. History of the following cosmetic treatments in the area(s) to be treated:
• Injectable filler of any type within the past 2 weeks
• Neurotoxins within the past week
• Ablative resurfacing laser treatment within the past 6 months
• Non-ablative, rejuvenating laser or light treatment within the past 6 months
• Chemical peel or dermabrasion within the past 3 months
18. Individuals undergoing concurrent therapy that, in the Investigator's opinion, would
interfere with the evaluation of the safety or efficacy of the study devices:
• Antiplatelet agents/anticoagulants (Coumadin, Heparin, Plavix, chronic NSAID use),
and/or
19. Psychiatric drugs that, in the Investigator's opinion, would impair the subject from
understanding protocol requirements or understanding and signing consent.
20. Individuals who are pregnant or nursing or those planning on becoming pregnant during
the study according to self-report.
21. Immunocompromised individuals or those currently using immunosuppressive medications
and/or radiation.
22. Individuals with uncontrolled disease such as asthma, diabetes, hyperthyroidism,
medically significant hypertension, or hypothyroidism. Those with multiple health
conditions may still be excluded from participation even if conditions are controlled.
23. Individuals with any planned surgeries, overnight hospitalization, and/or invasive
medical procedures planned during the study.
24. Individuals who, in the Investigator's opinion, have a history of poor cooperation,
unreliability or noncompliance with medical treatment.
25. Individuals who are unable to understand instructions or give informed consent
26. Individuals who have physical or psychological conditions which, in the opinion of the
Investigator, makes them unable to complete the study per protocol (e.g., not likely
to avoid other cosmetic treatments to area; not likely to stay in study for entire
duration due to other commitments; or those with concomitant conditions that may
develop symptoms that might confuse or confound study treatments or assessments).
A Study to See if Memantine Protects the Brain During Radiation Therapy Treatment for a Brain Tumor
This phase III trial compares memantine to usual treatment in treating patients with brain
tumors that are newly diagnosed or has come back (recurrent). Memantine may block receptors
(parts of nerve cells) in the brain known to contribute to a decline in cognitive function.
Giving memantine may make a difference in cognitive function (attention, memory, or other
thought processes) in children and adolescents receiving brain radiation therapy to treat a
primary brain tumor.
• >= 4 and < 18 years at time of study entry
• Patients must weigh 15 kg or greater at time of study entry
• Newly diagnosed or recurrent primary brain tumors that have not received prior cranial
radiotherapy
• Planned focal, cranial or craniospinal radiation treatment for a primary brain tumor
• The patient must have receptive and expressive language skills in English, French or
Spanish since the neurocognitive function and quality of life (QOL) assessment
instruments are available in these languages only
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 4 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 male; 0.8 female
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 male; 1 female
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 male; 1.2 female
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 male; 1.4 female
• Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 male; 1.4 female
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• The patient must be able to undergo magnetic resonance imaging
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Life expectancy of less than 18 months
• Pre-existing conditions:
• Any contraindication or allergy to memantine
• Intractable seizures while on adequate anticonvulsant therapy, defined as more
than one seizure per month for the past 2 months or since initiating
anticonvulsant therapy
• Co-morbid systemic illnesses, psychiatric conditions, social situations, or other
severe concurrent disease which, in the judgment of the investigator, would make
the patient inappropriate for entry into this study or interfere significantly
with the proper assessment of safety and toxicity of the prescribed regimens or
would limit compliance with the study requirements
• Patients with a motor, visual, or auditory condition that precludes computerized
neurocognitive assessments are not eligible to participate
• Patients with any medical condition or taking medications that lead to
alterations of urine pH towards the alkaline condition (e.g., renal tubular
acidosis, carbonic anhydrase inhibitors, sodium bicarbonate)
• Personal history of prior cranial or craniospinal radiotherapy is not allowed
• Note: Prior anti-cancer therapy including surgery, chemotherapy, targeted agents
are allowed as per standard of care clinical treatment guidelines
• Female patients who are pregnant are excluded since fetal toxicities and teratogenic
effects have been noted for the study drug. A pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who do not agree to use an
effective contraceptive method for the duration of their study participation
A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease (GATEWAY)
The objectives of this clinical trial are to assess, for up to 5 years, the safety,
tolerability and pharmacological activity of a single ascending doses of VTX-801, a gene
therapy, administered intravenously (IV) to adult patients with Wilson's Disease prior to and
following background WD therapy withdrawal.
• Male or female aged between 18 and 65 years
• Confirmed diagnosis of WD
• Treated for WD according to international recommendations with no current evidence for
inadequate treatment
• Stable WD for ≥ 1 year, defined as: (i) No significant change in neurologic
examination and in status of mood disorder and (ii) Stable laboratory parameters used
to assess copper metabolism
Main
Exclusion Criteria:
• ALT level ≥ 2 ULN that is not readily explained by extrinsic factors
• Total bilirubin > 1.5 x ULN in the absence of proven Gilbert's syndrome; in case of
Gilbert's syndrome, direct bilirubin > ULN
• INR > ULN
• Any signs of liver cirrhosis decompensation, including gastrointestinal bleed within 6
months (24 weeks) prior to screening/enrolment visit
• Patient has moderate or severe renal impairment defined as eGFR CKD-EPI < 60
mL/min/1.73 m2, or patient has nephritis or nephrotic syndrome
• Any history or current evidence of HIV-1, HIV-2, HTLV 1, or HTLV-2 infection
• Any history or current evidence of hepatitis B infection
• Any history of hepatitis C infection, unless previous viral RNA assays in two samples,
collected at least 6 months apart, are negative
• Positive QuantiFERON®-TB Gold tuberculosis test result
• Any concomitant disorder/condition •including hepatic disorders •or treatment
possibly interfering with the conduct or evaluation of the study
• Any history of diabetes
• Pregnancy or breastfeeding
• Body Mass Index ≥ 35 kg/m2
Other protocol defined Inclusion/ Exclusion criteria may apply
Two-Part Study for Dose Determination of SRP-5051 (Vesleteplirsen) (Part A), Then Dose Expansion (Part B) in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment (MOMENTUM)
This study will be comprised of 2 parts: 1) Part A (Multiple Ascending Dose [MAD]) will be
conducted to evaluate the safety and tolerability of SRP-5051 (vesleteplirsen) at MAD levels
to determine doses to be administered in Part B, and 2) Part B will be conducted to further
evaluate the SRP-5051 doses selected in Part A. Participants enrolling in Part B will be
those who completed Part A or Study 5051-102 and meet applicable eligibility criteria for
Part B, as well as additional participants who meet applicable eligibility criteria for
enrollment at the beginning of Part B.
Inclusion Criteria for participants previously treated with SRP-5051:
•Has received prior SRP-5051 treatment in Part A of this study or in Study 5051-102
Exclusion Criteria for participants previously treated with SRP-5051 and new participants
enrolling into Part B:
•Presence of other clinically significant illness, including cardiac, pulmonary, hepatic,
renal, hematologic, immunologic, or behavioral disease, or infection or malignancy or any
other condition that, in the Investigator's opinion, could interfere with participation in
the trial.
Inclusion Criteria for treatment-naïve participants enrolling into Part B:
• Has a genetic diagnosis of Duchenne muscular dystrophy (DMD) and an out-of-frame
deletion mutation of the DMD gene amenable to exon 51-skipping treatment.
• Has been on a stable dose of oral corticosteroids for at least 12 weeks prior to study
drug administration and the dose is expected to remain constant throughout the study
(except for modifications to accommodate changes in weight), or has not received
corticosteroids for at least 12 weeks prior to study drug administration.
• Has stable pulmonary function (forced vital capacity [FVC] ≥40% of predicted and no
requirement for nocturnal ventilation).
Exclusion Criteria for treatment-naive participants enrolling into Part B:
• History of hypomagnesemia within 12 weeks prior to Screening.
• Initiation or change of dosing (except for modifications to accommodate changes in
weight or changes in standard of care) within 12 weeks prior to Screening for any of
the following: angiotensin-converting enzyme inhibitors, angiotensin receptor-blocking
agents, β-blockers, or potassium.
• Initiation or change of dosing within 12 weeks prior to Screening for over-the-counter
preparations, such as herbal/nonherbal supplements, vitamins, minerals, and
homeopathic preparations.
• Has a left ventricular ejection fraction (LVEF) <40.0% based on an echocardiogram
(ECHO) performed within 12 weeks prior to Screening or at the Screening Visit.
• Treatment with any exon 51-skipping therapy within 4 weeks prior to Screening, or with
any experimental gene therapy for the treatment of DMD at any time.
Other inclusion/exclusion criteria apply.
Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation
This study will assess the safety and efficacy of Posoleucel for the treatment of adenovirus
(AdV) infection in pediatric and adult allo-HCT recipients receiving standard of care (SoC).
• Male or female >1 year of age.
• Has undergone allogeneic cell transplantation ≥21 days prior to randomization and
demonstrated engraftment with an absolute neutrophil count >500/mm^3, AND has one of
the following:
1. AdV viremia DNA ≥10,000 copies/mL at screening, OR
2. Two consecutive and rising AdV viremia DNA results of ≥1,000 copies/mL at
screening, AND
1. has absolute lymphocyte count <180/mm3, OR
2. has received T cell depletion.
• Contraceptive use by men and women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies and
refrain from donating sperm or eggs for at least 90 days after treatment completion.
• Willing and able to provide signed informed consent.
• Has an HLA type matching with at least 1 suitably matched and available posoleucel VST
line for infusion.
Exclusion Criteria:
• Grade >2 acute GVHD
• Ongoing therapy with high-dose systemic corticosteroids
• Grade 4 diarrhea
• Uncontrolled viral (other than AdV), bacterial, or fungal infection(s)
• Requirement for fraction of inspired oxygen >0.5 to maintain arterial oxygen
saturation >90% (via pulse oximetry) or need for mechanical ventilation.
• Prior therapy with anti-thymocyte globulin, alemtuzumab (Campath®), or other
immunosuppressive T cell monoclonal antibodies within 28 days prior to randomization.
• Prior donor lymphocyte infusion or CD34+ stem cell infusion within 21 days prior to
randomization.
• Use of vasopressors within 7 days prior to randomization.
• Use of any investigational antiviral agent, including brincidofovir, within 7 days
prior to randomization.
• Lactating female unwilling to discontinue nursing prior to randomization.
• Severe allergy to any component of posoleucel or history of severe prior reactions to
blood product transfusions.
• Positive for SARS-CoV-2 virus at screening.
The objective of this study is to determine if tAN therapy can reduce the median number of
days of oral morphine administered to an infant after start of treatment.
Inclusion Criteria
1. Neonates or infants >33 weeks gestational age with NOWS who have withdrawal scores
requiring morphine replacement therapy
2. Clinically stable or on minimal respiratory support (continuous positive airway
pressure [CPAP], nasal cannula, or room air)
3. Stable neonates who are dependent on opioids following extracorporeal membrane
oxygenation, severe illness, or brain injury will be included in this study as these
neonates represent a population in which tAN could minimize withdrawal while not
adding burden of pharmacotherapies
4. Congenital syndromes may be included if the infants do not have major, unrepaired
anomalies
Exclusion Criteria
1. Unstable infants or those requiring significant respiratory support
2. Repeated episodes of autonomic instability (apnea or bradycardia) which are not
self-resolving
3. Major unrepaired congenital anomalies impacting respiratory or cardiovascular system
4. Cardiomyopathy
5. Abnormal ear anatomy preventing the device to fit
6. Infants diagnosed with iatrogenic NOWS without intrauterine exposure
7. Infants two weeks of age or older (after birth)
8. Neonates who have received more than 6 methadone doses or 24 hours of methadone dosing
9. Infants who are wards of the state
10. Participant has any other significant disease or disorder which, in the opinion of the
Investigator, may either put the participants at risk because of participation in the
trial, or may influence the result of the trial, or the participant's ability to
participate in the trial
Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors
The purpose of this study is to further evaluate the efficacy and safety of niraparib in
patients with locally advanced or metastatic solid tumors and a pathogenic or likely
pathogenic tumor PALB2 (tPALB2) mutation.
• Participants must be at least 18 years of age or older.
• Participants must have a histologically or cytologically confirmed diagnosis of
locally advanced or metastatic solid tumor(s).
• Participants must have tested positive for a pathogenic or likely pathogenic tPALB2
gene mutation using a CLIA-certified laboratory as described in the Next-Generation
Sequencing (NGS) Laboratory Manual.
• Participants who have stable and asymptomatic Central Nervous System (CNS) disease
must be receiving a stable (for at least 7 days) or decreasing corticosteroid dose at
the time of study entry.
• Participants must submit fresh or archived (collected within 24 months of enrollment)
Formalin-Fixed Paraffin-Embedded (FFPE) tumor sample to the central laboratory for
post-enrollment confirmation of tPALB2 status.
• Participants must have received all standard therapies appropriate for their tumor
type and stage of disease or, in the opinion of the Investigator, the patient would be
unlikely to tolerate or derive clinically meaningful benefit from appropriate standard
of care therapy, or the participant has no satisfactory alternative treatments.
Exclusion Criteria:
• Participants have other active concomitant malignancy that warrants systemic,
biologic, or hormonal therapy.
• Participants who have ovarian or prostate cancer.
• Participants who have variants of undetermined significance (VUS), but not pathogenic
variants of PALB2, at the time of screening.
• Participants who relapsed while receiving platinum based therapy in the
adjuvant/curative setting.
• Participants progressing within 14-18 weeks while receiving platinum based therapy in
the metastatic setting.
• Participants who have received Poly (ADP-ribose) polymerase (PARP) inhibitor(s) in
prior lines of treatment.
• Participants with leptomeningeal disease, carcinomatous meningitis, symptomatic brain
metastases, or radiologic signs of CNS hemorrhage.
• Participants with germline or somatic BRCA1 or BRCA2 mutations.
• Participant has systolic blood pressure (BP) over 140 mmHg or diastolic BP over 90
mmHg, despite optimal medical therapy.
• Participants have previously or are currently participating in a treatment study of an
investigational agent within 3 weeks of the first dose of therapy preceding the study.
• Participants have received prior systemic cytotoxic chemotherapy, biological therapy,
or hormonal therapy for cancer, or received radiation therapy within 3 weeks of the
first dose therapy preceding the study.
Drug: Niraparib
Endometrial Cancer, Esophageal Cancer, Melanoma, Pancreatic Cancer, Metastatic Cancer, Head and Neck Cancer, Solid Tumor, Breast - Female, Colon, Corpus Uteri, Esophagus, Lung/Thoracic, Melanoma, skin, Other Urinary, Pancreas, Breast Tumor, Colon Tumor, Malignant, Lung Tumor, Urologic Cancer, Locally Advanced Solid Tumor
PALB2, Solid Tumor, Metastatic Solid Tumor, Locally Advanced Solid Tumor, Advanced Solid Tumor, Local Solid Tumor, PALB2 Mutation, Niraparib, tPALB2, tPALB2 Mutation, Pathogenic tumor, Lung Tumor, Breast Tumor, Colon Tumor, Zejula, Pancreatic Cancer, Urologic Cancer, Melanoma, Metastatic Cancer, Head and Neck Cancer, Endometrial Cancer, Esophageal Cancer
Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF (HFpEF)
This is a Phase 2A, randomized, parallel-group, placebo-controlled, double-blind, within
subject dose escalation trial with 3 dose levels of HU6 and placebo. Subjects will be
randomized (1:1) either to HU6 or placebo. Two dose levels will be administered in sequential
order (150 mg daily followed by 300 mg daily), each for 20 days, to reach the third and
highest dose of 450 mg daily if safety and tolerability are demonstrated at the lower 2
preceding doses. Administration of the 450 mg high dose will continue for a total of 94 days,
with a safety follow-up visit within ~14 days of the last dose.
1. Adult male or female, ≥40 years of age.
2. Competent to understand the information given in the Institutional Review Board (IRB)
or Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) and must
sign the form prior to the initiation of any study procedures.
3. Body mass index (BMI) ≥30 kg/m2;
4. Signs and symptoms of HF in the judgement of the Investigator, and meets the following
disease severity criteria:
a. KCCQ OSS ≤80; b. NYHA Classification Class II-III; c. Baseline peak VO2 ≤18
mL/kg/min for females or ≤20 mL/kg/min for males; d. Respiratory exchange ratio
(respiratory quotient) (RER [RQ]) at baseline of >1.0; e. Left ventricular ejection
fraction (EF) ≥50%; f. At least 1 of the following objective criteria for HF: i.
Documented hospitalization with HF as primary cause within in last year, or if greater
than the past year, then with addition of structural heart disease on echocardiography
(increased left atrial volume size or left ventricular hypertrophy, with sex-specific
cut-points as per Lang, 2015) as follows:
• Left ventricular hypertrophy (LVH):
1. Men: Either septal wall thickness (cm) either ≥1.1 or posterior wall
thickness ≥1.1;
2. Women: Either septal wall thickness (cm) either ≥ 1.0 or posterior wall
thickness ≥1.0;
• Left atrial dilation (LAD): AP dimension (cm): ≥4.0 in men; >3.8 in women; ii.
Pulmonary capillary wedge pressure (PCWP) at rest >15 mmHg (or left ventricular
end-diastolic pressure [LVEDP] ≥18 mmHg) or >25 mmHg (or 2.0 mmHg/L/min) with
exercise in the last year; iii. E/e' ratio ≥14 at septal annulus at rest on
Doppler and tissue Doppler imaging in the last year; or iv. Currently elevated
NT-proBNP defined as >125 pg/mL without atrial fibrillation and >350 pg/mL for
subjects with chronic controlled atrial fibrillation.
5. Participants should maintain their stable level of physical activity throughout the
duration of the study and must agree to not enroll in an exercise training program
during the study.
6. Participants should maintain their stable diet and no plan to enter into a weight loss
program prior to or during the course of the study.
7. Euthyroid as assessed by a thyroid profile utilizing thyroid stimulating hormone (TSH)
and free thyroxine (T4) testing at screening. Subjects with a stable history of
thyroid disease and who have been on stable doses of thyroid medications for a minimum
of 4 months can be enrolled.
8. Ambulatory (not wheelchair- or scooter-dependent) and able to perform upright exercise
testing including a 6 MWT.
9. Stable doses of medications (defined as no new medication or change in existing dose
of medication ≥50%) for 30 days prior to screening, with additional specific criteria
for the diuretics:
1. If treated with a loop or thiazide diuretic, must be on stable regimen, which
dose permits a flexible diuretic dosing schedule.
Exclusion Criteria:
1. Life expectancy <1 year due to non-cardiovascular reasons, in the judgement of the
Investigator.
2. History of malignancy within 5 years (except non-high-grade skin cancers,
carcinoma-in-situ, or low-grade prostate cancer).
3. Weight change (gain or loss) of ≥10 pounds either by self-reporting or documented
weight loss within the past 90 days.
4. Bariatric surgery prior to screening or planned bariatric surgery during the course of
the study.
5. Treatment with GLP-1 receptor antagonist begun within 1 year of screening.
6. Treatment with SGLT2 inhibitors begun within 6 months of screening.
7. Intolerance to MRI or with conditions contraindicated for MRI procedures including but
not limited to:
1. Having surgical clips/metallic implants/shrapnel/internal electric implants; or
2. Inability to fit into MRI scanner due to subject habitus or exceeding weight
tolerance limit of the scanner (generally, 350 or 400 lbs, dependent on
manufacturer); or
3. Claustrophobia: history of severe claustrophobia that would lead to inability to
conduct MRI.
8. Current acute decompensated HF requiring intravenous (IV) diuretics or recent (<1
month before screening) hospitalization for HF.
9. Primary cardiomyopathy (e.g., constrictive, restrictive, infiltrative, toxic,
hypertrophic [congenital], congenital, or any other primary cardiomyopathy, in the
judgement of the Investigator.
10. Active myocarditis (COVID-induced or otherwise).
11. Active collagen vascular disease.
12. Current greater than moderate left- or right sided valve disease, in the opinion of
the Investigator.
13. Planned cardiac surgery or catheter intervention during the time of trial
participation.
14. Prior documented EF <40% within the last 3 years.
15. Tachycardia (>110 beats/minute) at screening.
16. Atrial fibrillation or atrial flutter with an uncontrolled heart rate response or with
a resting heart rate greater than 110 bpm by ECG at screening. Subjects may rescreen
after appropriate adjustment of medication to manage the atrial fibrillation. A
maximum of 16 subjects with this condition can be enrolled in this study.
17. Untreated, life-threatening dysrhythmia.
Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma
This phase III trial studies how well response and biology-based risk factor-guided therapy
works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumor may
not need treatment until it progresses. In this case, observation may be sufficient.
Measuring biomarkers in tumor cells may help plan when effective treatment is necessary and
what the best treatment is. Response and biology-based risk factor-guided therapy may be
effective in treating patients with non-high risk neuroblastoma and may help to avoid some of
the risks and side effects related to standard treatment.
• Patients must be:
• < 12 months (< 365 days) of age at diagnosis with INRG stage L1; or
• < 18 months (< 547 days) of age at diagnosis with INRG stage L2 or stage Ms
neuroblastoma/ganglioneuroblastoma
• Enrollment on ANBL00B1 or APEC14B1 is required for all newly diagnosed patients
• Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene
neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International
Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN
non-amplified ganglioneuroblastoma verified by histology
• Patients must meet the specified criteria for one of the treatment groups defined
below; genomic features include MYCN gene amplification, segmental chromosome
aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number
gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index
• "Favorable" genomic features are defined by one or more whole-chromosome gains or
hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome
aberrations as defined above
• "Unfavorable" genomic features are defined by the presence of any segmental
chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic
copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this
includes copy neutral loss of heterozygosity (LOH)
• Only patients with MYCN non-amplified tumors are eligible for this study
• Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1
neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin
• Patients with non-adrenal primaries are eligible, but must have positive uptake
on metaiodobenzylguanidine (MIBG) scan or elevated catecholamine metabolites
(urine or serum) to support the diagnosis of neuroblastoma
• No prior tumor resection or biopsy
• Group A will be further split into two subsets, which are mutually exclusive, for
statistical purposes
• Group A1:
• > 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in
greatest diameter OR
• Patients less than 6 months of age with an adrenal primary tumor > 3.1 and <
5 cm in greatest diameter OR
• < 12 months of age with a non-adrenal primary site < 5 cm in greatest
diameter
• Group A2: =< 6 months of age with an adrenal primary site and tumor =< 3.1 cm in
greatest diameter.
• Group B: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage L2
neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• No life threatening symptoms or no impending neurologic or other organ function
compromise (e.g. epidural or intraspinal tumors with existing or impending
neurologic impairment, periorbital or calvarial-based lesions with existing or
impending cranial nerve impairment, anatomic or mechanical compromise of critical
organ function by tumor [abdominal compartment syndrome, urinary obstruction,
etc.]); horner syndrome is not considered neurologic compromise
• No prior tumor resection, tumor biopsy ONLY
• Only patients with both favorable histology and favorable genomic features will
remain on study as part of Group B; the institution will be notified of
histologic and genomic results within 3 weeks of specimen submission on ANBL00B1
or APEC14B1
• Group C: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage Ms
neuroblastoma/ganglioneuroblastoma
• No prior radiotherapy or chemotherapy, with the exception of dexamethasone, which is
allowed
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with MYCN amplified tumors are not eligible
• Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive
diagnostic procedure
• Group A and C patients, not required to undergo tumor biopsy, who do not enroll on
ANBL1232 within 4 weeks of confirmatory imaging study
The iCat2, GAIN (Genomic Assessment Informs Novel Therapy) Consortium Study
This research study is evaluating the use of specialized testing of solid tumors including
sequencing. The process of performing these specialized tests is called tumor profiling. The
tumor profiling may result in identifying changes in genes of the tumor that indicate that a
particular therapy may have activity. This is called an individualized cancer therapy (iCat)
recommendation. The results of the tumor profiling and, if applicable, the iCat
recommendation will be returned.
• Age -- Age ≤ 30 years at time of initial qualifying solid tumor diagnosis
• Diagnosis -- Histologic diagnosis of solid malignancy (excluding brain tumors and
lymphoma) that meets at least one of the following criteria:
• Refractory, defined as tumor progression after initiation of standard first line
therapy without having achieved a prior partial or complete remission OR Biopsy
proven residual disease at the completion of planned standard initial front-line
therapy.
• Recurrent, defined as tumor progression after achieving a prior partial or
complete remission
• Newly diagnosed high risk disease, defined as having an expected event free
survival of < 50% at 2 years.
• Lacks definitive diagnosis or classical genomic findings after histologic review
and standard molecular testing (rare tumor group).
• Examples include (eligibility not limited to these examples):
• Histology typically associated with a fusion in which fusion is not detected.
• Ewing-like sarcoma
• Undifferentiated sarcoma
• Inflammatory myofibroblastic tumor without ALK fusion
• Infantile fibrosarcoma without NTRK fusion
• Specimen Samples
• Sufficient tumor specimen available to meet the minimum requirements for
profiling from diagnosis or progression / recurrence
--- OR
• Surgery / biopsy planned as part of clinical care that is anticipated to yield
sufficient material to meet the minimum requirements for profiling; OR
• Patient has already had molecular profiling and patient has not yet started
matched targeted therapy based on the report .
Exclusion Criteria:
• No Therapy Planned
-- Patients who have declined further anticancer therapy will be excluded.
• Performance Status
-- Patients with Lansky (age < 16 years) or Karnofsky (age ≥16 years) score < 50 will
be excluded.
• Life Expectancy -- Patients with anticipated life expectancy < 3 months will be
excluded.
Genetic: Genetic testing and GAIN report
Sarcoma, Pediatric Solid Tumor, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Heart, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate
Chlorthalidone (CTD) may produce various metabolic disturbances, including hypokalemia,
activation of Renin-Angiotensin- Aldosterone (RAA) system, oxidative stress, dyslipidemia,
Fibroblast growth factor 23 (FGF23) synthesis, and magnesium depletion. These factors may
interact with each other to contribute to the development of insulin resistances and
metabolic syndrome. Smaller studies have suggested that Potassium magnesium Citrate (KMgCit)
can ameliorate CTD- induced metabolic side effects independent of correction of hypokalemia.
This study will tests if KMgCit ameliorates CTD induced metabolic effects independent of
correction of hypokalemia.
Call 214-648-5940 danielle.pittman@utsouthwestern.edu or Call 214-648-5005 studyfinder@utsouthwestern.edu, Ashley.Murillo@UTSouthwestern.edu
Wanpen Vongpatanasin
17620
All
21 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT02665117
STU 092015-058
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Treated or untreated stage I hypertension
Exclusion Criteria:
• Diabetes mellitus,
• Renal impairment (serum creatinine > 1.4 mg/dL),
• Any heart diseases such as congestive heart failure, sustained arrhythmia, or coronary
heart disease,
• Chronic regular NSAID use,
• Allergy to thiazide diuretics,
• Gastro-esophageal reflux disease (GERD) requiring treatment with acid reducing agents
or antacid more than once a week,
• Esophageal-gastric ulcer or history of gastrointestinal bleeding,
• Chronic diarrhea, vomiting,
• Excessive sweating,
• Unprovoked hypokalemia (serum K < 3.5 mmol/L) or hyperkalemia (serum K > 5.3 mmol/L),
• Abnormal liver function test (Aspartate transaminase (AST) or Alanine transaminase
(ALT) above upper limit of normal range),
• Subjects on any potassium supplement on a regular basis for any reason, such as
patients with primary aldosteronism,
• Pregnancy,
• History of major depression, bipolar disorder, or schizophrenia,
• History of substance abuse,
• Gout,
• Metabolic alkalosis, with serum bicarbonate > 32 meq/L,
• Severe dietary salt restriction, less than1/2 spoonful or 50 meq sodium/day.
• Patient with Claustrophobia will not have MRI but can still participate in the study
without MRI
• Metal implants will not have MRI but can still participate in the study without MRI
Computer Training Program for Younger Patients With a Brain Tumor Who Underwent Radiation Therapy
This randomized clinical trial studies how well an adaptive computerized cognitive training
program works compared to a non-adaptive computerized cognitive training program in treating
younger patients with brain tumor who underwent radiation therapy. Providing a computer
training program may improve the well-being and quality of life of patients with cognitive
(physical and mental) function difficulties caused by radiation therapy to the brain.
• Patient must be newly diagnosed or relapsed/progressed with a brain tumor that has not
previously been treated with CRT
• Note: COG therapeutic study participation is not required for ACCL10P1 enrollment
• Patient enrollment must occur within 4 calendar months following completion of CRT
• Reminder: after patient enrollment, baseline testing followed by randomization
must occur within 2-4 months after completion of CRT
• The patient must have an identified caregiver who is willing and able to oversee the
training practice during the intervention period (ie, for 5-9 weeks starting
approximately 3 months after completion of CRT)
• The patient must have access to a telephone and phone number where they can be reached
• The patient and caregiver must have reading, speaking and listening comprehension of
English
• All patients and/or their parents or legal guardians must sign a written informed
consent (patient assent is also recommended when applicable according to each
institution's policy)
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with pontine glioma are not eligible
• Patients with an estimated survival of less than one year are not eligible
• Patients with a history of traumatic brain injury prior to tumor diagnosis are not
eligible
• Patients with a motor, visual, or auditory handicap that prevents computer use (e.g.,
unresolved posterior fossa syndrome) are not eligible to participate in this trial
• Patients with full-scale intelligence quotient (IQ) < 70 per previous testing OR
existing diagnosis of/educational classification as a student with an intellectual
disability are not eligible
Procedure: Cognitive Assessment, Other: Computer-Assisted Cognitive Training, Procedure: Psychosocial Assessment and Care, Other: Quality-of-Life Assessment, Other: Questionnaire Administration
Brain Neoplasm, Recurrent Brain Neoplasm, Brain and Nervous System
A Study to Compare the Long-term Outcomes After Two Different Anaesthetics (TREX)
There is considerable evidence that most general anaesthetics modulate brain development in
animal studies. The impact is greater with longer durations of exposure and in younger
animals. There is great controversy over whether or not these animal data are relevant to
human clinical scenarios.
The changes seen in preclinical studies are greatest with GABA agonists and NMDA antagonists
such as volatile anaesthetics (eg sevoflurane), propofol, midazolam, ketamine, and nitrous
oxide. There is less evidence for an effect with opioid (such as remifentanil) or with alpha
2 agonists (such as dexmedetomidine).
Some, but not all, human cohort studies show an association between exposure to anaesthesia
in infancy or early childhood and later changes in cognitive tests, school performance or
risk of developing neurodevelopmental disorders. The evidence is weak due to possible
confounding.
A recent well designed cohort study (the PANDA study) comparing young children that had
hernia repair to their siblings found no evidence for a difference in a range of detailed
neuropsychological tests. In that study most children were exposed to up to two hours of
anaesthesia. The only trial (the GAS trial) has compared children having hernia repair under
regional or general anesthesia and has found no evidence for a difference in neurodevelopment
when tested at two years of age. The GAS and PANDA studies confirm the animal data that short
exposure is unlikely to cause any neurodevelopmental impact.
The impact of longer exposures is still unknown. In humans the strongest evidence for an
association between surgery and poor neurodevelopmental outcome is in infants having major
surgery. However, this is also the group where confounding is most likely.
The aim of our study is to see if a new combination of anaesthetic drugs results in a better
long-term developmental outcome than the current standard of care for children having
anaesthesia expected to last 2 hours or longer.
Children will be randomised to receive either a low dose
sevoflurane/remifentanil/dexmedetomidine or standard dose sevoflurane anaesthetic.
They will receive a neurodevelopmental assessment at 3 years of age to assess global
cognitive function.
• Younger than 2 years (chronological age)
• Scheduled for anaesthesia that is expected to last at least 2 hours (and/or total
operating room time is scheduled to be at least 2.5 hours)
• Has a legally acceptable representative capable of understanding the informed consent
document and providing consent on the participant's behalf.
Exclusion Criteria:
• Known neurologic, chromosomal or congenital anomaly which is likely to be associated
with poor neurobehavioural outcome
• Existing diagnosis of behavioural or neurodevelopmental disability
• Prematurity (defined as < 36 weeks gestational age at birth)
• Birth weight less than 2 kg.
• Congenital cardiac disease requiring surgery
• Intracranial neurosurgery and intracranial craniofacial surgery (isolated cleft lip is
not an exclusion)
• Previous cumulative exposure to general anaesthesia exceeding 2 hours
• Planned future cumulative exposure to anaesthesia exceeding 2 hours before the age of
3 years.
• Any specific contra-indication to any aspect of the protocol
• Previous adverse reaction to any anaesthetic
• Circumstances likely to make long term follow-up impossible
• Living in a household where the primary language spoken at home is not a language in
which we can administer the Wechsler Preschool and Primary School Intelligence Scale
• Planned postoperative sedation with any agent except opioids (e.g. benzodiazepines,
dexmedetomidine, ketamine, barbiturates, propofol, clonidine, chloral hydrate, and
other non-opioid sedatives). For example if such sedation is planned for
post-operative ventilation
The US food and Drug Administration (FDA) originally approved INTACS prescription inserts in
April 1999 for the correction of low levels of nearsightedness (-1.00 to -3.00 diopters).
Additional clinical data have shown that INTACS are safe for the treatment of keratoconus,
in July 2004, FDA approved INTACS inserts for the treatment of keratoconus as a Humanitarian
Use Device (FDA approval letter attached). The statute and the implementing regulation of
FDA (21 CFR 814.124 (aj) require IRB review and approval before a HUD is used.INTACS
prescription inserts are composed of two clear segments, each having an arc length of 150°,
they are manufactured form a biomedical material called polymethylmethacrylate (PMMA) and
are available in three thicknesses. Two INTACS inserts ranging from 0.250mm to 0.350mm may
be implanted depending on the orientation of the cone and the amount of myopia and
astigmatism to be reduced.
Who have experienced a progressive deterioration in their vision, such thot they can no
longer achieve adequate functional vision on a daily basis with their contact lenses or
spectacles; Who are 21 years of age or older; Who have clear central corneas; Who have a
corneal thickness of 450 microns or greater at the proposed incision site; Who have
corneal transplantation as the only remaining option to improve their functional vision.
Exclusion Criteria:
Who have abnormally thin corneas or who have a corneal thickness of 449 microns or less at
the proposed incision site;
Patients with collagen vascular, autoimmune or immunodeficiency disease;
Pregnant or nursing patients;
Presence of ocular conditions, such as recurrent corneal erosion syndrome or corneal
dystrophy, that my predispose the patient to future complications;
Patients who are taking on or more of following medications: isotretinoin (Accutane);
amiodarone HCL (Cordarone).
Safety Study of Cord Blood Units for Stem Cell Transplants
Background:
- Cord blood is blood that is taken from the umbilical cord and placenta of healthy newborns
after childbirth. The cord blood collected from a baby is called a cord blood unit. Cord
blood units are stored frozen in public cord blood banks. About 10,000 cord blood
transplants have been performed in children and adults for blood cancers and other diseases
in the world. These transplants have helped save lives and improve treatments. However, not
all available units of cord blood have been collected, stored, and licensed according to
specific government requirements. These unlicensed units can still be used in transplant,
but they can only be given as part of specific research studies. This study will evaluate
the safety of giving these unlicensed units by recording any problems that may occur during
and after giving the cord blood.
Objectives:
- To test the safety and effectiveness of unlicensed cord blood units in people who need
stem cell transplants.
Eligibility:
- Individuals who are scheduled to have a stem cell transplant.
Design:
- Participants will be screened with a medical history and physical exam.
- Participants will receive the cord blood unit as part of their stem cell transplant
procedure. The transplant will be performed according to the current standard of care
for the procedure.
- After the transplant, participants will be monitored for up to 1 year. Any problems or
side effects from the transplant will be treated as necessary. All outcomes will be
reported to the National Cord Blood Program and to the Center for International Blood
and Marrow Transplant.
• INCLUSION CRITERIA:
• Patients of any age or either gender with indications for receipt of investigational
HPC-CORD BLOOD who are participating in an NIH-IRB approved clinical trial for
unrelated hematopoietic stem cell transplantation.
• Signed informed consent (and assent when applicable).
EXCLUSION CRITERIA:
• Patients who are receiving licensed CB products (only)
• Patients who are receiving unlicensed CB products from other CB banks (i.e. NMDP)
Difluoromethylornithine (DFMO) will be used in an open label, single agent, multicenter,
study for patients with neuroblastoma in remission. In this study subjects will receive 730
Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 ± 250 mg/m2 BID (strata 1,
2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study. This study will focus on
the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to
prevent recurrence.
• All patients must have a pathologically confirmed diagnosis of neuroblastoma, < 30.99
years of age and classified as high risk at the time of diagnosis. Exception: patients
who are initially diagnosed as non-high-risk neuroblastoma, but later converted
(and/or relapsed) to high risk neuroblastoma are also eligible.
• All patients must be in complete remission (CR):
1. No evidence of residual disease on scan
2. No evidence of disease metastatic to bone marrow.
• Specific Criteria by Stratum:
Stratum 1/1B: All patients must have completed standard upfront therapy that replicates
treatment which patients who were enrolled on ANBL0032 received, including:
intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by:
consolidation with high-dose chemotherapy with stem cell transplant and radiotherapy,
followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;.
All subjects on Stratum 1/B must have also met the following criteria:
• A pre-transplant disease status evaluation that met International Neuroblastoma Response
Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR
(partial response) for primary site, soft tissue metastases and bone metastases. Patients
who meet those criteria must also meet the protocol-specified criteria for bone marrow
response prior to transplant as outlined below: No more than 10% tumor involvement (based
on total nucleated cellular content) seen on any specimen from a bilateral bone marrow
aspirate/biopsy.
Stratum 2: Neuroblastoma that is in first complete remission following standard upfront
therapy different from that described for Stratum 1.
Stratum 3: Neuroblastoma that failed to have a response of at least PR following induction
chemotherapy and surgical resection of the primary tumor, but that has achieved CR
following additional therapy.
Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s).
• Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of
mandatory disease staging must be performed:
• Tumor imaging studies including
• Bilateral bone marrow aspirates and biopsy
• This disease assessment is required for eligibility and preferably should be done
within 2 weeks prior to enrollment, but must be done within a maximum of 4 weeks
before enrollment.
• Timing from prior therapy:
Stratum 1/1B: Enrollment no later than 60 days after completion of upfront therapy, (last
dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance
therapy.
Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent
therapy.
• Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients
must have a life expectancy of ≥ 2 months.
• All clinical and laboratory studies for organ functions to determine eligibility must
be performed within 7 days prior to enrollment unless otherwise indicated below.
• Patients must have adequate organ functions at the time of registration:
• Hematological: Total absolute phagocyte count ≥1000/μL
• Liver: Subjects must have adequate liver function
• Renal: Adequate renal function
• Females of childbearing potential must have a negative pregnancy test. Patients of
childbearing potential must agree to use an effective birth control method. Female
patients who are lactating must agree to stop breast-feeding.
• Written informed consent in accordance with institutional and FDA (food and drug
administration) guidelines must be obtained from all subjects (or patients' legal
representative).
Exclusion Criteria:
• BSA (Body Surface Area) of <0.25 m2.
• Investigational Drugs: Subjects who are currently receiving another investigational
drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are
not eligible. Subjects must have fully recovered from hematological and bone marrow
suppression effects of prior chemotherapy.
• Infection: Subjects who have an uncontrolled infection are not eligible until the
infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study, or in whom compliance is likely to be
suboptimal, should be excluded.
Study to Determine the Pharmacokinetics and Pharmacodynamic Effects of Phenylephrine on BP Via IV
The primary objective of this study is to evaluate the dose effect of Phenylephrine
Hydrochloride Injection on the treatment of clinically relevant decreased blood pressure in
the pediatric population, ≥12 to 16 year old patients undergoing general and neuraxial
anesthesia.
The secondary objectives are to describe changes in blood pressure and heart rate, time to
onset and to maximal response, and the duration of response; to assess the safety of the
product in this population; and to characterize the pharmacokinetics of phenylephrine
hydrochloride.
1. Subject's age is between ≥12 and 16 years, inclusive
2. Subject is scheduled for a procedure that requires general or neuraxial anesthesia
3. Subjects must have normal or clinically acceptable physical exam
4. Subjects with controlled diabetes prior to entry must have a mean systolic/diastolic
office blood pressure ≤128/78 mmHg (sitting, after 5 minutes of rest)
5. Females must have a urine or serum pregnancy test (Human Chorionic Gonadotropin) that
is negative at Screening and Day 1
6. Subject's parent or legal guardian gives informed consent and subject gives assent.
Exclusion Criteria:
1. Subject has a contraindication to vasoconstrictor therapy for control of blood
pressure
2. Subject has participated in other clinical trials for investigational drugs and/or
devices within 30 days prior to enrollment
3. Subject has any serious medical condition which, in the opinion of the investigator,
is likely to interfere with study procedures
4. Subjects who have a history of any clinically significant local or systemic infectious
disease within four weeks prior to initial treatment administration
5. Subjects who are positive for hepatitis B surface antigen or hepatitis C antibody
6. Subjects taking antihypertensive medication
7. Subject is moribund (death is likely to occur in less than 48 hours)
8. Females who are pregnant, nursing or unwilling to use/practice adequate contraception.
Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia
The purpose of Phase 1b of this study is to:
- Asses the safety, tolerability and activity of carfilzomib, alone and in combination
with induction chemotherapy, in children with relapsed or refractory acute lymphoblastic
leukemia (ALL).
- Determine the maximum tolerated dose (MTD) and to recommend a phase 2 dose of
carfilzomib in combination with induction chemotherapy.
The purpose of Phase 2 of this study is to compare the rate of complete response (CR) of
carfilzomib in combination with vincristine, dexamethasone, PEG asparaginase, daunorubicin
(VXLD) at the end of induction therapy to an appropriate external control.
1. Age 21 years or younger at the time of initial ALL diagnosis and age > 1 year at the
time of study treatment initiation.
2. Subjects must have a diagnosis of relapsed or refractory ALL with ≥ 5% blasts in the
bone marrow (M2 or M3 disease), with or without extramedullary disease.
-To be eligible, subjects must have had 1 or more prior therapeutic attempts, defined
as:
• Early first relapse (< 36 months from original diagnosis) after achieving a CR
(B-ALL) or first relapse any time following the original diagnosis after
achieving a CR (T-ALL)
• First refractory bone marrow relapse occurring any time after original diagnosis
after achieving a CR (ie, ≥1 failed attempt to induce a second remission) OR
• Relapse after achieving a CR following the first or subsequent relapse (i.e., ≥ 2
relapses) OR
• Failing to achieve a CR from original diagnosis after at least 1 induction
attempt
3. Subjects must have fully recovered from the acute toxic effects of all previous
chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
4. Subjects must have a serum creatinine level that is ≤ 1.5 × institutional upper limit
of normal (ULN) according to age. If serum creatinine level is > 1.5 × ULN, the
subject must have a calculated creatinine clearance or radioisotope glomerular
filtration rate (GFR) ≥ 70 mL/min/1.73 m2.
5. Adequate liver function, defined as both of the following:
• Total bilirubin ≤ 1.5 × institutional ULN except in the presence of Gilbert
Syndrome
• Alanine aminotransferase (ALT) ≤ 5 × institutional ULN
6. Performance status: Karnofsky or Lansky scores ≥ 50 for subjects > 16 years old or ≤
16 years old, respectively.
Phase 2
Inclusion Criteria:
1. Subject's legally acceptable representative has provided informed consent when the
subject is legally too young to provide informed consent and the subject has provided
written assent based on local regulations and/or guidelines prior to any
study-specific activities/procedures being initiated.
2. Age greater than or equal to 1 month to less than 21 years. Subjects greater than or
equal to 18 years must have had their original diagnosis at less than 18 years of age.
3. Subjects must be diagnosed with relapsed or refractory relapsed ALL.
4. Subjects must have a documented first remission, less than or equal to 5% blasts in
the bone marrow (M1 bone marrow) and no evidence of extramedullary disease.
5. T-cell ALL with bone marrow relapse (defined as greater than or equal to 5% leukemia
blasts in bone marrow) or refractory relapse with or without extramedullary disease.
OR B-cell ALL bone marrow relapse or refractory relapse (defined as greater than or
equal to 5% leukemia blasts in bone marrow) after having received a targeted B-cell
immune therapy (eg, blinatumomab, inotuzumab or a CAR-T therapy) with or without
extramedullary disease..
6. Adequate liver function: bilirubin less than or equal to 1.5 x upper limit of normal
(ULN), alanine aminotransferase (ALT) less than or equal to 5 x ULN.
7. Adequate renal function: serum creatinine less than or equal to 1.5 x ULN or
glomerular filtration rate (GFR) greater than or equal to 70 mL/min/1.73 m^2; or for
children less than 2 years of age, greater than or equal to 50 mL/min/1.73 m^2.
8. Adequate cardiac function: shortening fraction greater than or equal to 30% or
ejection fraction greater than or equal to 50%.
9. Karnofsky (subjects greater than or equal to 16 years of age) or Lansky (subjects 12
months to less than 16 years of age) performance status greater than or equal to 50%.
10. Subjects must have fully recovered from the acute toxic effects of all previous
chemotherapy, immunotherapy, or radiotherapy treatment before enrollment (for example:
recovery from gastrointestinal toxicity may occur more rapidly than less reversible
organ toxicities such as sinusoidal obstruction syndrome or non-infectious
pneumonitis, for serious prior toxicities recommended discussion with Amgen medical
monitor).
11. Life expectancy of greater than 6 weeks per investigator's judgement at time of
screening.
Phase 1b Key
Exclusion Criteria:
1. Known allergy to any of the drugs used in the study (Subjects who have had a previous
allergy to PEG-asparaginase and if able, may receive Erwinia asparaginase at the
investigator's discretion)
2. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
3. Left ventricular fractional shortening < 30%
4. History of ≥ Grade 2 pancreatitis
5. Active graft-versus-host disease requiring systemic treatment
6. Positive culture for or other clinical evidence of infection with bacteria or fungus
within 14 days of the initiation of study treatment
7. Down Syndrome
8. Prior therapy restrictions:
• Subjects must have completed therapy with granulocyte-colony stimulating factor
(G-CSF) or other myeloid growth factors at least 7 days before study treatment
initiation, or at least 14 days before study treatment initiation, if pegylated
myeloid growth factors were administered.
• Subjects must have completed any type of active immunotherapy (e.g., tumor
vaccines) at least 42 days before study treatment initiation.
• Subjects must have received the last dose of a non-monoclonal antibody biologic
agent at least 7 days before study treatment initiation.
• At least 3 antibody half-lives must have elapsed since the last dose of
monoclonal antibody (e.g., 66 days for rituximab and 69 days for epratuzumab)
before subjects may initiate study treatment.
• Subjects must not have received other antineoplastic agents with therapeutic
intent, excluding hydroxyurea and antimetabolites administered as part of
maintenance chemotherapy, within 7 days prior to study treatment initiation.
9. Hepatitis B infection with positive hepatitis B DNA
Phase 2
Exclusion Criteria:
1. Prior treatment with carfilzomib.
2. Prior treatment with a proteasome inhibitor (other than carfilzomib) within less than
3 months of enrollment or to which a subject did not respond (response is defined as
bone marrow with less than 5% blasts).
3. Treatment with a chemotherapy regimen including a vinca alkaloid, steroid,
L-asparaginase, and anthracycline combination with or without other chemotherapy
agents within 2 months of enrollment (eg VXLD, VPLD, R3).
4. Intolerance, hypersensitivity, or inability to receive any of the chemotherapy
components of the VXLD regimen. An exception is allowed for allergy to asparaginase
products if Erwinia asparaginase is unable to be administered,
5. Autologous HSCT within 6 weeks prior to start of study treatment.
6. Allogeneic HSCT within 3 months prior to start of study treatment.
7. Active GVHD requiring systemic immune suppression.
8. Less than 30 days from discontinuation of immune suppressive therapy administered for
the treatment of acute or chronic GVHD.
9. Isolated extramedullary relapse.
10. Positive bacterial or fungal infection within 14 days of enrollment (except for
documented line infection, line has been removed, and blood culture after line removal
is negative for 5 days prior to first dose of induction therapy). Antibiotics may be
administered for prophylaxis as per institutional standards up to and after
enrollment.
11. Subjects with less than 3 antibody half-lives since the last dose of monoclonal
antibody (eg, 66 days for rituximab, 69 days for epratuzumab, inotuzumab for 36 days),
prior to first dose of investigational product must be discussed with the Amgen
medical monitor and may be allowed to enroll based on extent of disease or evidence of
rapidly rising peripheral or bone marrow blast counts.
12. Cell-based immunotherapy (eg, donor leucocyte infusion, CAR-T cells, tumor vaccines)
within 42 days prior to first dose of investigational product. If the Amgen medical
monitor agrees, an exception may be granted to the 42-day requirement for subjects
with rapidly rising peripheral or bone marrow blast counts.
13. Down's syndrome.
14. Presence of another active cancer.
15. History of grade greater than or equal to 2 pancreatitis within 6 months to screening.
16. Unresolved toxicities from prior anticancer therapy, defined as not having resolved to
CTCAE version 4.03 grade 1 or to levels dictated in the eligibility criteria apart
from alopecia or toxicities from prior anticancer therapy that are considered
irreversible and do not trigger another exclusion criterion (defined as having been
present and stable for greater than 4 weeks).
17. Antitumor therapy (chemotherapy, investigational agents, molecular-targeted therapy)
within 7 days of day 1 of induction. Exception: hydroxyurea to control peripheral
blood leukemic cell counts is allowed until start of investigational product.
18. Active viral infection, including but not limited to cytomegalovirus (CMV), Hepatitis
B infection with positive serum hepatitis surface antigen or hepatitis B DNA, HIV,
Hepatitis C with detectable hepatitis C RNA. Subjects who have previously received a
stem cell transplant must be screened for CMV infection, unless both subject and donor
are known to be CMV negative.
19. Currently receiving treatment in another investigational device or product study, or
less than 14 days since ending treatment on another investigational device or product
study.
20. Uncontrolled arrhythmias or screening ECG with corrected QT interval (QTc) of greater
than 470 msec.
21. History or evidence of any other clinically significant disorder, condition or disease
(with the exception of those outlined above) that, in the opinion of the investigator
or Amgen physician, if consulted, would pose a risk to subject safety or interfere
with the study evaluation, procedures or completion.
22. Female subject is pregnant or breastfeeding or planning to become pregnant or
breastfeed during treatment and for an additional 6 months after the last dose of any
study treatment or for 12 months after last dose of cyclophosphamide if administered
during optional consolidation cycle.
23. Female subjects of childbearing potential unwilling to use 1 highly effective method
of contraception during treatment and for an additional 6 months after the last dose
of any study treatment or for 12 months after last dose of cyclophosphamide if
administered during optional consolidation cycle.
24. Female subjects of childbearing potential with a positive pregnancy test assessed at
Screening by a serum or urine pregnancy test.
25. Male subjects with a female partner of childbearing potential who are unwilling to
practice sexual abstinence (refrain from heterosexual intercourse) or use a condom
with spermicide during treatment and for an additional 6 months after the last dose of
any study treatment, even if they have undergone a successful vasectomy.
26. Male subjects with a pregnant partner who are unwilling to practice abstinence or use
a condom with spermicide during treatment, for duration of pregnancy, and for an
additional 6 months after the last dose of any study treatment.
27. Male subjects unwilling to abstain from donating semen or sperm during treatment and
for an additional 6 months after the last dose of any study treatment.
28. Known allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib;
for a complete listing of Captisol-enabled drugs, see the Ligand Pharmaceuticals, Inc.
website).
A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors (GARNET)
This is a multicenter, open-label, first-in-human Phase 1 study evaluating the
anti-programmed death receptor 1 (anti-PD-1) antibody TSR-042 in patients with advanced solid
tumors who have limited available treatment options. The study will be conducted in 2 parts:
dose escalation and cohort expansion. The cohort expansion may include up to 5 tumor types,
including endometrial and Non-Small Cell Lung cancer.
• Patient is at least 18 years of age
• Patient with advanced or metastatic solid tumor and has disease progression after
treatment with available therapies that are known to confer clinical benefit or who
are intolerant to treatment that meets the following requirements for the part of the
study they will participate in:
1. Part 1: Patient with any advanced or metastatic solid tumor
2. Part 2A: Patient with any advanced or metastatic solid tumor
3. Part 2B: Patient with Non-Small Cell Lung Cancer (NSCLC) and Endometrial cancers
• Female patients, if of childbearing potential, must have a negative serum pregnancy
test within 72 hours prior to the date of the first dose of study medication.
• Female patients of childbearing potential must agree to use 2 adequate methods of
contraception with their partner starting with the screening visit through 150 days
after the last dose of study therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 for Part 1 and ≤ 1
for Part 2. Adequate organ function.
Exclusion Criteria:
• Patient has received prior therapy with an anti- programmed death receptor 1
(anti-PD-1), anti-PD-1- ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD- L2)
agent.
• Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous
meningitis. Note: Patients with previously treated brain metastases may participate
provided they are stable (without evidence of progression by imaging for at least 4
weeks prior to the first dose of study treatment and any neurologic symptoms have
returned to baseline), have no evidence of new or enlarging brain metastases, and are
clinically stable off steroids for at least 7 days prior to study treatment.
Carcinomatous meningitis precludes a patient from study participation regardless of
clinical stability.
• Known additional malignancy that progressed or required active treatment within the
last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell
cancer (SqCC) of the skin that has undergone potentially curative therapy, or in situ
cervical cancer.
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• Known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or
hepatitis C (eg, hepatitis C virus ribonucleic acid (HCV RNA) (qualitative) is
detected).
• Active autoimmune disease that has required systemic treatment in the past 2 years
(ie, with use of disease- modifying agents, corticosteroids, or immunosuppressive
drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
• History of interstitial lung disease.
Aripiprazole for Bipolar Disorder and Alcohol Use Disorder
The investigators will conduct a 12-week, randomized, double-blind, parallel-group,
placebo-controlled study of aripiprazole in 132 persons with Alcohol Use Disorder (AUD) and
bipolar I or II disorder, currently depressed or mixed phase. Primary Aim will be to assess
change in alcohol use by the Timeline Followback (TLFB) method. Secondary Aim will include
change in alcohol craving using the Penn Alcohol Craving Scale (PACS). Changes in psychiatric
symptoms (mania/hypomania and depression) and predictors of response will be assessed.
Participants with ≥ 1 drinking day at week 12 will be enrolled in a 4-week extension phase
with an upward titration to 30 mg/day for those in the active treatment group. The placebo
group will remain on placebo.
Subjects will be discontinued from the study if any of the following conditions occurs:
change in diagnosis to other than bipolar I or II disorder and AUD, development of active
suicidal or homicidal ideation with plan and intent, worsening in mood symptoms, that in the
opinion of the investigators requires discontinuation, pregnancy, development of severe or
life-threatening medical condition, involuntary psychiatric hospitalization or incarceration,
significant alcohol withdrawal (e.g. delirium tremens) based on clinical judgment (increases
in Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores will initiate a
careful clinical assessment of possible worsening of withdrawal symptoms), or cocaine or
amphetamine-positive urine drug screen during the study.
• Outpatient men and women age 18-65 years old with bipolar I, II, Not Otherwise
Specified (NOS) disorder, or Schizoaffective Bipolar Type
• If diagnosed with Bipolar I, Bipolar NOS w/history of mania or Schizoaffective
Disorder Bipolar Type, current mood stabilizer therapy (lithium, valproic acid,
lamotrigine, gabapentin) with stable dose for > 28 days prior to randomization.
• Baseline Barrett Impulsiveness Scale-11 Score of > 62 (above average impulsivity)
• Systolic BP > 100 and < 165 and Diastolic BP > 60 and < 105 with no evidence of
orthostatic hypotension
• Current Diagnosis of Alcohol Use Disorder with at least moderate severity
• Alcohol use of an average of 15 drinks per 7 days in the past 28 days prior to intake
for men, and an average of 8 drinks per 7 day period in the past 28 days prior to
intake for women
• Current mood stabilizer therapy with stable dose for > 28 days
• Fluent in English or Spanish
Exclusion Criteria:
• Baseline Hamilton Rating Scale for Depression (HRSD) or Young Mania Rating Scale
(YMRS) scores > 35
• Mood disorders other than bipolar I, II, NOS or schizoaffective disorder bipolar type
(e.g. cyclothymic disorders, schizophrenia, schizoaffective disorder depressive type,
or unipolar depression based on the SCID), other disorders, e.g. anxiety disorders,
will be allowed.
• Current diagnosis of amphetamine or cocaine use disorder or a cocaine or amphetamine
positive baseline urine sample.
• Evidence of clinically significant alcohol withdrawal symptoms
• Current treatment with an atypical antipsychotic
• Current treatment with naltrexone, acamprosate, disulfiram, or topiramate in the last
28 days
• Prior treatment with Aripiprazole within the last year or lifetime history of
intolerable side effects to Aripiprazole
• Vulnerable populations (e.g. pregnant, nursing, cognitively impaired, incarcerated.)
• Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar
score of ≥ 10.
• High risk for suicide
• Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 3 times upper
limit of normal
• Current use of Cytochrome P450 3A4 inducing medication (e.g. carbamazepine, rifabutin,
rifampin, ritonavir).
• Use of other substances (besides cocaine/amphetamine) is allowed if the use disorder
is no greater than moderate severity and alcohol is the self-identified substance of
choice.
• History of neuroleptic malignant syndrome or tardive dyskinesia.
More specific inclusion and exclusion criteria will be discussed with participant at
baseline assessment.
STaph Aureus Resistance-Treat Early and Repeat (STAR-TER) (STAR-TER)
To evaluate the micro-biologic efficacy and safety of a streamlined treatment for early onset
methicillin-resistant staphylococcus aureus (MRSA) in patients with cystic fibrosis.
1. Male or female ≥ 2 and ≤ 45 years of age at the Screening Visit.
2. Documentation of a CF diagnosis as evidenced by one or more clinical features
consistent with the CF phenotype and one or more of the following criteria:
1. sweat chloride ≥ 60 milliequivalents/liter by quantitative pilocarpine
iontophoresis test (QPIT)
2. two well-characterized mutations in the cystic fibrosis transmembrane conductive
regulator (CFTR) gene
3. abnormal nasal potential difference(NPD) (change in NPD in response to a low
chloride solution and isoproteronol of less than -5 mV)
3. First OR early MRSA colonization defined as:
1. First MRSA colonization: first documented isolation of MRSA from respiratory
tract occurred ≤ 6 months prior to screening
2. Early MRSA colonization: MRSA was previously isolated from the respiratory tract
≤ 2 times over the past 3.5 years, but this was followed by at least 1 year of
documented negative cultures for MRSA
4. MRSA is available to the central laboratory •either the incident MRSA isolate from
the clinic visit or the subject is MRSA positive at the screening visit
5. Clinically stable with no significant changes in health status within the 14 days
prior to screening
6. Written informed consent (and assent when applicable) obtained from subject or
subject's legal representative and ability for subject to comply with the requirements
of the study
Exclusion Criteria:
1. Received antibiotics with activity against MRSA within 28 days prior to screening
2. Use of an investigational agent within 28 days prior to screening
3. For subjects ≥ 6 years of age: FEV1 at screening < 25% of predicted for age based on
the Wang (males < 18 years, females < 16 years) or Hankinson (males ≥ 18 years,
females ≥ 16 years) standardized equations
4. MRSA from the screening culture or the most recent clinical care visit within 6 months
prior to screening resistant to TMP/SMX
5. History of intolerance to topical chlorhexidine or mupirocin
6. History of intolerance to both TMP/SMX and minocycline
7. < 8 years of age and allergic or intolerant to TMP/SMX
8. ≥ 8 years of age and allergic or intolerant to TMP/SMX and MRSA isolate (from
screening or clinical care visit)is resistant to minocycline
9. For females of child bearing potential: pregnant, breastfeeding, or unwilling to use
barrier contraception through Day 42 of the study
10. Subjects with history of abnormal renal function will need screening labs showing
normal function Abnormal renal function is defined as estimated creatinine clearance
<50 mL/min using the:
1. Bedside Schwartz Equation for subjects <18 years of age, and
2. Levey Glomerular filtration rate (GFR) Equation for subjects ≥ 18 years of age.
11. Subjects with a history of abnormal liver function will need to have screening labs
showing normal transaminases. Liver dysfunction is defined as ≥3x upper limit of
normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase
(ALT) or abnormal synthetic function
12. History of solid organ or hematological transplantation
13. Presence of a condition or abnormality that in the opinion of the Investigator would
compromise the safety of the patient or the quality of the data.
Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients
with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come
back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a
monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab
attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill
them.
• Patients must be >= 1 year and < 22 years of age at the time of enrollment
• Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL),
with >= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
• NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL)
are eligible if they have an M2 or M3 marrow at the time of enrollment on this
study
• Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing
showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH)
testing or other molecular method
• Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by
local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of
CD22 using a bright fluorophore such as phycoerythrin [PE] is strongly recommended)
• In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate
is unable to be performed due to patient clinical status, flow cytometry of
peripheral blood specimen may be substituted if the patient has at least 1,000/uL
circulating blasts; alternatively, CD22 expression may be documented by
immunohistochemistry of a bone marrow biopsy specimen
• Patients with one of the following:
• Second or greater relapse;
• Primary refractory disease with at least 2 prior induction attempts;
• First relapse refractory to at least one prior re-induction attempt
• Any relapse after HSCT (Cohort 1 ONLY)
Patients with Down syndrome are eligible ONLY for Cohort 1 with:
• Any of above disease status, OR
• First relapse with no prior re-induction attempt NOTE: Patients with Down syndrome or
prior HSCT are NOT eligible for Cohort 2 combination therapy
• Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy
attempts including two different tyrosine kinase inhibitors (TKIs)
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy, defined as resolution of all such toxicities to =< grade 2
or lower per the inclusion/exclusion criteria prior to entering this study. Apply
to Cohort 2:
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. For
agents not listed, the duration of this interval must be discussed with the study
chair and the study-assigned Research Coordinator prior to enrollment.
• A waiting period prior to enrollment is not required for patients receiving
standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine,
6MP, and/or methotrexate).
• A waiting period is not required for patients receiving a single dose of
intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior
to enrollment
• >= 14 days must have elapsed after the completion of other cytotoxic therapy,
with the exception of hydroxyurea, for patients not receiving standard
maintenance therapy. For patients who previously received calaspargase pegol, >=
21 days must have elapsed after the last dose. Additionally, patients must have
fully recovered from all acute toxic effects of prior therapy.
• Note: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior
to the start of protocol therapy.
• Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced
platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of
agent. For agents not listed, the duration of this interval must be discussed with the
study chair and the study-assigned research coordinator prior to enrollment.
• Anti-cancer agents that are antibodies: >= 21 days must have elapsed from infusion of
last dose of antibody, and toxicity related to prior antibody therapy must be
recovered to grade =< 1. There is an exception for blinatumomab infusions, for which
patients must have been off for at least 3 days and all drug related toxicity must
have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >=
14 days must have elapsed since last dose of corticosteroid. A waiting period prior to
enrollment is not required for patients receiving corticosteroid for leukemia
therapy/cytoreduction.
• Radiotherapy: >= 2 weeks must have elapsed since local palliative radiation therapy
(XRT) (small port); >= 3 months must have elapsed if prior cranial or craniospinal XRT
was received, if >= 50% of the pelvis was irradiated, or if total body irradiation
(TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow
irradiation was given.
• Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must have
elapsed since stem cell transplant and at least 30 days from donor lymphocyte
infusion. Patient must have had no more than one previous HSCT and currently have no
evidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT is
allowed.
• Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsed
from the last CAR-T cell infusion
• Patients must have a performance status corresponding to Eastern Cooperative
Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years
of age and Lansky for patients =< 16 years of age; patients who are unable to
walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing the performance score
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or
• A serum creatinine based on age/gender as follows:
• 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
• 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
• 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
• 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
• 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
• Direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5
x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L
Exclusion Criteria:
• Patients with any prior history of SOS irrespective of severity
• Patients with isolated central nervous system (CNS), testicular, or any other
extramedullary site of relapse
• Patients who have been previously treated with inotuzumab ozogamicin
• Patients who have previously received HSCT (Cohort 2 only)
• Patients with Down syndrome (Cohort 2 only)
• History of allergic reaction attributed to compounds of similar or biologic
composition to inotuzumab ozogamicin or other agents in the study
• Note: Patients with history of allergy to pegaspargase/calaspargase pegol are
eligible for enrollment on Cohort 2 (dose levels 1 and -1) if Erwinia formulation
of asparaginase can be obtained
• If Cohort 2 is enrolling at dose level -2, then patients who cannot receive
asparaginase due to prior allergy, toxicity, or lack of access may enroll
• NOTE: patients on AALL1621 are not eligible to co-enroll on AALL1931
• Patients with active optic nerve and/or retinal involvement are not eligible; patients
who are presenting with visual disturbances should have an ophthalmologic exam and, if
indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal
involvement
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving or plan to receive other anti-cancer agents
(except hydroxyurea, which may be continued until 24 hours prior to start of protocol
therapy, and intrathecal chemotherapy)
• Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are
receiving cyclosporine, tacrolimus, or other agents to prevent either
graft-versus-host disease post bone marrow transplant or organ rejection
post-transplant are not eligible for this trial; at least 3 half-lives must have
elapsed after the last dose of GVHD or anti-rejection medications
• Patients who are currently receiving or plan to receive corticosteroids except as
described below
• Systemic corticosteroids may be administered for cytoreduction up to 24 hours
prior to the start of protocol therapy, (Cohort 1 only) for all patients,
corticosteroids may be administered as a premedication for inotuzumab ozogamicin
and as treatment for allergic reactions or for physiologic replacement/stress
dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids
are not allowed for other indications
• Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections;
testing to prove negative status is not required for enrollment unless it is deemed
necessary for usual medical care of the patient
• Patients who have an active uncontrolled infection defined as:
• Positive bacterial blood culture within 48 hours of study enrollment;
• Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with
clinical signs of infection; fever that is determined to be due to tumor burden
is allowed if patients have documented negative blood cultures for at least 48
hours prior to enrollment and no concurrent signs or symptoms of active infection
or hemodynamic instability
• A positive fungal culture within 30 days of study enrollment or active therapy
for presumed invasive fungal infection
• Patients may be receiving IV or oral antibiotics to complete a course of therapy
for a prior documented infection as long as cultures have been negative for at
least 48 hours and signs or symptoms of active infection have resolved; for
patients with clostridium (C.) difficile diarrhea, at least 72 hours of
antibacterial therapy must have elapsed and stools must have normalized to
baseline
• Active viral or protozoal infection requiring IV treatment
• Patients known to have one of the following concomitant genetic syndromes: Bloom
syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman
(Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failure syndrome
• There have been no human studies of inotuzumab ozogamicin in pregnant women and no
reports of exposure in utero; based on nonclinical safety studies, inotuzumab
ozogamicin has the potential to impair human male and female fertility and to
adversely affect human embryo fetal development; women of childbearing potential
should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin;
there is no information regarding the presence of inotuzumab ozogamicin in human milk,
the effects on the breast-fed infant, or the effects on milk production; because of
the potential for adverse reactions in breast-fed infants, women should not
breast-feed during treatment with inotuzumab ozogamicin and for at least 2 months
after the final dose
• Female patients of childbearing potential are not eligible unless a negative
pregnancy test result has been obtained within 7 days prior to enrollment
• Female patients who are sexually active and of reproductive potential are not
eligible unless they agree to use an effective contraceptive method for the
duration of their study participation and for 8 months after the last dose of
inotuzumab ozogamicin
• Men with female partners of childbearing potential should use effective
contraception during treatment with inotuzumab ozogamicin and for at least 5
months after the last dose of inotuzumab ozogamicin
• Lactating females are not eligible unless they agree not to breastfeed their
infants
Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma
Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
This partially randomized phase II/III trial studies how well, in combination with surgery,
cisplatin and combination chemotherapy works in treating children and young adults with
hepatoblastoma or hepatocellular carcinoma. Drugs used in chemotherapy, such as cisplatin,
doxorubicin, fluorouracil, vincristine sulfate, carboplatin, etoposide, irinotecan,
sorafenib, gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. Giving combination chemotherapy may kill more tumor cells than one type of
chemotherapy alone.
• Patients in Group F must have a body surface area (BSA) >= 0.6 m^2
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age; patients who are unable to walk because of
paralysis, but who are up in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score
• Patients must be newly diagnosed with histologically-proven primary pediatric hepatic
malignancies including hepatoblastoma or hepatocellular carcinoma, except as noted
below; patients with a diagnosis of hepatocellular neoplasm, not otherwise specified,
should be classified and treated per hepatoblastoma treatment arms; note that rapid
central pathology review is required in some cases; please note: all patients with
histology as assessed by the institutional pathologist consistent with pure small cell
undifferentiated (SCU) HB will be required to have testing for INI1/SMARCB1 by
immunohistochemistry (IHC) according to the practices at the institution
• Patients with histology consistent with pure SCU must have positive INI1/SMARCB1
staining
• For all Group A patients, WDF status as determined by rapid review will be used to
further stratify patients to Group A1 or A2
• For Groups B, C and D, rapid review is required if patients are either >= 8 years
of age or have an alphafetoprotein (AFP) =< 100 at diagnosis
• For all Groups E and F patients, rapid central pathology review is required
• In emergency situations when a patient meets all other eligibility criteria and has
had baseline required observations, but is too ill to undergo a biopsy safely, the
patient may be enrolled without a biopsy
• Clinical situations in which emergent treatment may be indicated include, but are
not limited to, the following circumstances:
• Anatomic or mechanical compromise of critical organ function by tumor (e.g.,
respiratory distress/failure, abdominal compartment syndrome, urinary
obstruction, etc.)
• Uncorrectable coagulopathy
• For a patient to maintain eligibility for AHEP1531 when emergent treatment is
given, the following must occur:
• The patient must have a clinical diagnosis of hepatoblastoma, including an
elevated alphafetoprotein (AFP), and must meet all AHEP1531 eligibility
criteria at the time of emergent treatment
• Patient must be enrolled on AHEP1531 prior to initiating protocol therapy; a
patient will be ineligible if any chemotherapy is administered prior to
AHEP1531 enrollment
• Note: If the patient receives AHEP1531 chemotherapy emergently PRIOR to
undergoing a diagnostic biopsy, pathologic review of material obtained in the
future during either biopsy or surgical resection must either confirm the
diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be
included in the analysis of the study aims
• Patients may have had surgical resection of the hepatic malignancy prior to
enrollment; all other anti-cancer therapy for the current liver lesion is prohibited
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60
mL/min/1.73 m^2 or
• A serum creatinine based on age/gender as follows:
• Age: maximum serum creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male and female)
• 6 months to < 1 year: 0.5 (male and female)
• 1 to < 2 years: 06 (male and female)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Total bilirubin =< 5 x upper limit of normal (ULN) for age
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
< 10 x upper limit of normal (ULN) for age
• Shortening fraction of >= 28% by echocardiogram (for patients on
doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior
to study enrollment) or
• Ejection fraction of >= 47% by echocardiogram or radionuclide angiogram (for patients
on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks
prior to study enrollment)
• Group F patients only: QT/corrected QT (QTc) interval =< 450 milliseconds for males
and =< 470 milliseconds for females (assessed within 8 weeks prior to study
enrollment)
• Normal pulmonary function tests (including diffusion capacity of the lung for carbon
monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at
rest, known requirement for supplemental oxygen) (for patients receiving chemotherapy
[Groups A, B, C, D, E2, F]); for patients who do not have respiratory symptoms or
requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents,
local therapy (embolization, radiofrequency ablation, and laser); therefore, patients
with a pre-disposition syndrome who have a prior malignancy are not eligible
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving other anticancer agents
• Patients with uncontrolled infection
• Patients who previously received a solid organ transplant, other than those who
previously received an orthotopic liver transplantation (OLT) as primary treatment of
their hepatocellular carcinoma
• Patients with hypersensitivity to any drugs on their expected treatment arm
• Group C: Patients who have known deficiency of dihydropyrimidine dehydrogenase (DPD)
• Group D:
• Patients with chronic inflammatory bowel disease and/or bowel obstruction
• Patients with concomitant use of St. John's wort, which cannot be stopped prior
to the start of trial treatment
• Group F:
• Patients with peripheral sensitive neuropathy with functional impairment
• Patients with a personal or family history of congenital long QT syndrome
• These criteria apply ONLY to patients who may receive chemotherapy (all groups other
than Group E1):
• Female patients who are pregnant since fetal toxicities and teratogenic effects
have been noted for several of the study drugs; a pregnancy test is required for
female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
• Note for Group F: patients of childbearing potential should use effective
birth control during treatment with sorafenib and for at least 2 weeks after
stopping treatment
Myeloma-Developing Regimens Using Genomics (MyDRUG) (MyDRUG)
The MyDRUG study is a type of Precision Medicine trial to treat patients with drugs targeted
to affect specific genes that are mutated as part of the disease. Mutations in genes can lead
to uncontrolled cell growth and cancer. Patients with a greater than 25% mutation to any of
the following genes; CDKN2C, FGFR3, KRAS, NRAS, BRAF V600E, IDH2 or T(11;14) can be enrolled
to one of the treatment arms. These arms have treatments specifically directed to the mutated
genes. Patients that do not have a greater than 25% mutation to the genes listed can be
enrolled to a non-actionable treatment arm.
The genetic sequencing of the patient's tumor is required via enrollment to the MMRF002
study: Clinical-grade Molecular Profiling of Patients with Multiple Myeloma and Related
Plasma Cell Malignancies. (NCT02884102).
• Willing to be registered into the pomalidomide (POMALYST®) Risk Evaluation and
Mitigation Strategy (REMS®) program
• Enrolled in the MMRF002 Molecular Profiling Protocol (NCT02884102) with report less
than 120 days old
• Disease free of prior malignancies for ≥ 3 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or
breast, or prostate cancer not requiring therapy
• High risk patients with relapsed refractory multiple myeloma (RRMM), who have:
• received at least one prior but no more than 3 prior therapies
• exposed to both a PI and an IMiD
• had early relapse after initial treatment Early relapse as defined by at least
one of the following: (Relapse is defined as the IMWG uniform response)
1. Relapse within 3 years of initiation of induction chemo therapy for post
autologous stem cell transplantation (ASCT) followed by maintenance, or 18
months if unmaintained after ASCT
2. Within 18 months of initial non-ASCT based therapy
• Patients must have progressed after their most recent treatment and require therapy
for myeloma
• Females of reproductive potential must have a negative pregnancy test at baseline, be
non-lactating, and willing to adhere to scheduled pregnancy testing
• Females of reproductive potential and males must practice and acceptable method of
birth control
• Laboratory values obtained ≤ 14 days prior to registration:
• Absolute neutrophil count (ANC) ≥ 1000/ul
• Hemoglobin (Hgb) ≥ 8 g/dl
• Platelet (PLT) ≥ 75,000/ul
• Total bilirubin <1.5 x upper limit of normal (ULN) or if total bilirubin is >1.5
x ULN, the direct bilirubin must be ≤ 2.0 mg/dL
• Aspartate aminotransferase (AST) <3 x ULN
• Creatinine Clearance ≥ 30 mL/min
Measurable disease of Multiple Myeloma (MM) as defined by at least one of the following:
• Serum monoclonal protein ≥ 0.5 g by protein electrophoresis
• ≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
• Serum immunoglobulin free light chain (FLC) ≥10 mg/dL AND abnormal serum
immunoglobulin kappa to lambda FLC ratio
• Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease)
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2
• Ability to take aspirin, warfarin, or low molecular weight heparin
Sub-Protocol
Inclusion Criteria:
Refer to each respective Sub Protocol for additional inclusion criteria.
Exclusion Criteria:
Patients will be ineligible for this study if they meet any one of the following criteria:
• Aggressive multiple myeloma requiring immediate treatment as defined by:
• Lactate dehydrogenase (LDH) > 2 times ULN
• Presence of symptomatic extramedullary disease or central nervous system
involvement
• Hypercalcemia >11.5 mg/dl
• Acute worsening of renal function (CrCl < 30 ml/min) directly related to myeloma
relapse
• Any neurological emergency related to myeloma
• Clinical symptoms of hyperviscosity related to monoclonal protein
• Involved serum free light chain > 100 mg/dL (1000 mg/L) in the setting of prior
diagnosis of cast nephropathy
• Infection requiring systemic antibiotic therapy or other serious infection within 14
days of enrolment
• Known hypersensitivity or development of erythema nodosum if characterized by a
desquamating rash while taking thalidomide, lenalidomide, pomalidomide or similar
drug. Known allergy to any of the study medications, their analogues, or excipients in
the various formulations of the agents
• Prior Ixazomib/Pomalidomide/Dexamethasone combination therapy
• Pregnant or breast-feeding females
• Serious medical or psychiatric illness, active alcoholism, or drug addiction that may
hinder or confuse compliance, interfere in the completion of treatment per protocol,
or follow-up evaluation
• Active hepatitis A, B or C viral infection or known human immunodeficiency virus (HIV)
infection
• Concurrent symptomatic amyloidosis or plasma cell leukemia
• POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein (M-protein) and skin changes]
• Residual side effects to previous therapy > Grade 1 prior to initiation of therapy
(Alopecia any grade and/or neuropathy Grade 2 without pain are permitted)
• Prior allogeneic or ASCT within 12 weeks of initiation of therapy. Prior allogeneic
stem cell transplant with active graft-versus-host disease (GVHD)
• Prior experimental therapy within 14 days of protocol treatment or 5 half-lives of the
investigational drug, whichever is longer
• Prior anticancer therapy within 14 days of initiation of protocol therapy
(Dexamethasone/ 40mg/day) for a maximum of 4 days before screening is allowed
• Prior major surgical procedure or radiation therapy within 4 weeks of the initiation
of therapy (this does not include limited course of radiation used for management of
bone pain within 7 days of initiation of therapy).
• Known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that
limit the ingestion or Gastro Intestinal (GI) absorption of drugs administered orally
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,
unstable angina, or myocardial infarction within the past 6 months
• Other co-morbidity, which would interfere with patient's ability to participate in
trial or that confounds the ability to interpret data from the study
Sub-Protocol
Exclusion Criteria:
Refer to each respective Sub Protocol for additional exclusion criteria.
• Postnatal age 48 hours -21 days
• Infant 22 0/7 to 28 6/7 weeks gestation at birth
• sPDA, as defined as:
1. Mild, Moderate, or Severe Clinical Criteria with Small or Moderate size PDA on
echocardiogram
2. Mild or Moderate Clinical Criteria with Large PDA on echocardiogram
Exclusion Criteria:
• Cardiopulmonary compromise
• Known congenital heart disease (besides atrial septal defect or ventricular septal
defect)
• Known pulmonary malformation (e.g. congenital lobar emphysema, congenital pulmonary
adenomatous malformation)
• Any condition which, in the opinion of the investigator, would preclude enrollment
Other: Active Treatment, Other: Expectant Management
Moderately Preterm Infants With Caffeine at Home for Apnea (MoCHA) Trial (MoCHA)
The objective of this study is to evaluate the effect of continuing treatment with caffeine
citrate in the hospital and at home in moderately preterm infants with resolved apnea of
prematurity on days of hospitalization after randomization.
• Inborn and outborn infants of 29 0/7 to 33 6/7 weeks gestational age at birth
• admitted to hospitals of the NICHD NRN who, are at time of enrollment:
• ≤35 6/7 weeks post-menstrual age at the time of randomization
• Receiving caffeine with plan to discontinue treatment or just discontinued caffeine
treatment
• Receiving feeds at a volume of ≥120 ml/kg/day by oral and/or tube feeding
• Ability to start study medication within 72 hours after stopping caffeine
Exclusion Criteria:
• On respiratory therapy (oxygen more than room air equivalent for high altitude sites,
nasal cannula, continuous positive pressure ventilation, and/or mechanical
ventilation)
• Infants who would otherwise be discharged home on apnea monitor due to underlying
disease or family history, including history of a sibling with sudden infant death
syndrome
• Parental request for apnea monitor
• Congenital heart disease other than atrial septal defect, ventricular septal defect,
or patent ductus arteriosus
• Neuromuscular conditions affecting respiration
• Major congenital malformation and/or genetic disorder
• Plans to transfer to a non-NRN site before discharge
• Unable to obtain parental or guardian consent
Trial of Curcumin to Prevent Progression of Low-risk Prostate Cancer Under Active Surveillance
This is a prospective study to determine if the use of curcumin randomized against placebo
will reduce cancer progression in patients with prostate cancer undergoing active
surveillance.
• Age between 40-89 years
• Biopsy proven, low-risk, localized prostate cancer (minimum of 8 cores)
• May have had biopsy within last 12 months ≤4 cores involved with cancer
• Gleason score ≤6 with no Gleason pattern 4
• Clinical stage T1c-T2a/b
• Serum PSA ≤15 ng/ml
• Life expectancy > 5 years
Exclusion Criteria:
• Any previous prostate cancer treatment (radiotherapy, chemotherapy, hormonal therapy,
oral glucocorticoids, GnRH analogues, prostatectomy)
• Concurrent or previous use within 6 months of screening of any 5α-reductase inhibitor
• Use of anabolic steroids or drugs with antiandrogenic properties
• Prostate volume >150 grams
• Patients who are taking antiplatelet, anticoagulant agents or have a history of a
bleeding disorder. Patients taking 81 mg of Aspirin will be allowed to enroll with
close observation
• History of gastric or duodenal ulcers or untreated hyperacidity syndromes. Patients on
stable doses (2 months of therapy) of GERD medication allowed.
• Patients who are currently taking Curcumin and are unwilling to stop or plan to take
Curcumin during the study
• Patients with a history of gallbladder problems or gallstones or biliary
obstruction,unless patient had cholecystectomy
Drug: Curcumin, Drug: Placebo
Prostate Cancer, Prostate
prostate cancer, active surveillance, curcumin
UT Southwestern; Parkland Health & Hospital System