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APVO436 Phase 1b/2 Study in Patients With Newly Diagnosed AML
A multi-center, open-label, dose-finding study of five dose levels of APVO436 in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE1
NCT06634394
STU-2024-1192
Inclusion Criteria:
* 1. Age ≥18 years. 2. Patient must have confirmation of AML based on 2016 World Health Organization (WHO) criteria and not been previously treated.
• Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry \[IHC\]). Confirmation at diagnosis is acceptable.
• Patient must be considered ineligible for induction therapy defined by at least one of the following:
• ≥75 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3
• Cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
• Pulmonary disorder (e.g., DLCO ≤65% or FEV1 ≤65%)
• Creatinine clearance 30-45 mL/min based on Cockcroft-Gault or Modified of Diet in Renal Disease (MDRD) formular
• Hepatic disorder with total bilirubin between 1.5 and 3 times the ULN 5. Patient must have a projected life expectancy of ≥12 weeks
Exclusion Criteria:
• Patient has received treatment with the following:
• A hypomethylating agent, venetoclax, and/or chemotherapeutic agent for AML, myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or myelodysplastic/myeloproliferative neoplasms (MPS/MPN)
• CAR-T cell therapy or history of allogeneic hematopoietic stem cell transplant (HSCT)
• Experimental therapies for MDS or AML
• Patient is currently participating in another interventional research study.
• Patient has history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation.
• Patient has acute promyelocytic leukemia.
• Patient has a current autoimmune disorder requiring immunosuppressive therapy such as systemic (oral or IV) steroid therapy \>10 mg methylprednisolone daily or its equivalent
• Patient is receiving concurrent corticosteroid therapy as an anticancer drug (any dose).
• Patient has known active CNS involvement with AML. Patients who received intrathecal chemotherapy for prophylaxis of AML in the CNS prior to enrollment may enroll in this study.
• Creatinine clearance \<30ml/min based on Cockcroft-Gault or MDRD formular.
• Bilirubin of \>3xULN in the absence of Gilbert's Syndrome.
• AST and/or ALT \>3 times the ULN.
DRUG: APVO436, DRUG: Venetoclax, DRUG: Azacitidine
Acute Myeloid Leukemia (AML), Myeloid and Monocytic Leukemia
Acute Myeloid Leukemia
UT Southwestern
A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination with Venetoclax/Azacitidine, Venetoclax, or 7+3 in Patients with AML
This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3 for two different molecularly-defined arms, NPM1-m and KMT2A-r.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE1
NCT05735184
STU-2023-0858
Key
Inclusion Criteria:
* Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Adequate liver, renal, and cardiac function according to protocol defined criteria
* A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention
Key Exclusion Criteria:
* Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic leukemia
* Known history of BCR-ABL alteration
* Advanced malignant hepatic tumor \[for patients receiving ven/aza combination\]
* Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery
* Active central nervous system (CNS) involvement by AML.
* Clinical signs/symptoms of leukostasis or WBC \> 25,000 / microliter. Hydroxyurea and/or leukapheresis are permitted to meet this criterion
* Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia
* Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection
* For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia, or non-HMA therapy for prior myelodysplastic syndrome
* For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug
* Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol
* Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF) \>480 ms on triplicate ECGs
* Uncontrolled infection
* Women who are pregnant or lactating
* An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing DRUG: Ziftomenib, DRUG: Venetoclax, DRUG: Azacitidine, DRUG: Daunorubicin, DRUG: Cytarabine
Acute Myeloid Leukemia, Mixed Lineage Acute Leukemia, Mixed Lineage Leukemia Gene Mutation, Mixed Phenotype Acute Leukemia, Refractory AML, AML With Mutated NPM1, Acute Myeloid Leukemia Recurrent, Acute Myeloid Leukemia, in Relapse, NPM1 Mutation, KMT2Ar, Myeloid Sarcoma, Myeloid and Monocytic Leukemia
UT Southwestern
Canakinumab for the Prevention of Progression to Cancer in Patients with Clonal Cytopenias of Unknown Significance, IMPACT Study
This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS). CCUS is a blood condition defined by a decrease in blood cells. Blood cells are composed of either red blood cells, white blood cells, or platelets. In patients with CCUS, blood counts have been low for a long period of time. Patients with CCUS also have a mutation in one of the genes that are responsible for helping blood cells develop. The combination of genetic mutations and low blood cell counts puts patients with CCUS at a higher risk to develop blood cancers in the future. This transformation from low blood cell counts to cancer may be caused by inflammation in the body. Canakinumab is a monoclonal antibody that may block inflammation in the body by targeting a specific antibody called the anti-human interleukin-1beta (IL-1beta).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE2
NCT05641831
STU-2024-0699
Inclusion Criteria:
* Patients with age \>= 18 with high-risk CCUS
* Must meet ALL the following criteria:
* Unexplained, clinically meaningful cytopenias (greater than 4 months) in one or more of the following lineages: erythroid cells, neutrophils, platelets. Clinically meaningful cytopenia is institution specific and threshold may vary on age, sex, and race. Decision-making should depend upon lab values specific to the institution and supersede public works. Based upon published work, significant cytopenias are defined as the following:
* Erythroid Cells:
* Hemoglobin \< 11 g/dL
* White Blood Cells:
* Absolute Neutrophil Count \< 1800/microL and \> 500/microL
* Platelets:
* Platelet Count \< 150,000/microL and \> 50,000/microL
* MDS criteria not fulfilled
* No other evidence of hematological malignancy
* No or only mild (\< 10%) bone marrow dysplasia
* Blast cells \< 5% detected via morphologic examination of blood and/or bone marrow smears which can also be supported by flow cytometry and/or immunohistochemical studies
* Any of the following:
* Isolated somatic spliceosome mutation at any VAF (SRSF2, SF3B1, U2AF1, or ZRSR2)
* Isolated TP53 mutation greater than 5% VAF
* At least 1 mutation in TET2, DMNT3A, or ASXL1 at any VAF coupled with at least 1 other known myeloid pathogenic somatic mutation or known pathogenic germline mutation that predisposes to myeloid malignancy as determined by next generation sequencing and bone marrow biopsy
* A TET2, DMNT3A, or ASXL1 greater than 10% VAF coupled with another TET2, DMNT3A, or ASXL1 greater than 10% VAF
* The presence of two or more known myeloid pathogenic somatic or germline mutations (other than TET2, ASXL1, DMNT3A, TP53, or spliceosome mutations) greater than 10% VAF
* Ability to understand and willingness to sign the written informed consent document
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Patients with a history of hypertension or active hypertension are strongly encouraged to optimize blood pressure control
* Creatinine clearance greater than 45 ml/min using Cockcroft-Gault
* Total bilirubin =\< 1.5 x ULN
* Aspartate transaminase (AST) \< 3 x ULN
* Alanine transaminase (ALT) \< 3 x ULN
Exclusion Criteria:
* Concurrent malignancy requiring active systemic therapy
* Diagnosis of MDS or any other myeloid malignancy in the patient's lifetime
* History of Hypersensitivity to canakinumab or drug of a similar class
* Active infection requiring prompt evaluation and treatment or history of recurrent infections
* Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (via positive or indeterminate central laboratory \[lab\] results)
* Subjects with active tuberculosis. In subjects without active tuberculosis, if the results of the evaluation require treatment per local guidelines, then the treatment should be initiated before randomization (unless otherwise required by Health Authorities or Institutional Review Board (IRB) in which case curative treatment must be completed prior to screening)
* Subjects with suspected or proven immunocompromised state or infections. If the results of this screening per local treatment guidelines or clinical practice require treatment for said infection then the patient is not eligible. Suspected or proven immunocompromised states or infections include:
* Those with any other medical condition such as active infection, treated or untreated, which in the opinion of the investigator places the subject at an unacceptable risk for participation in immunomodulatory therapy
* Known history of testing positive for human immunodeficiency virus (HIV) infections. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
* Allogeneic bone marrow or solid organ transplant (history of any or within a certain period of time?)
* Those requiring systemic or local treatment with any immune modulating agent in doses with systemic effects e.g.:
* Prednisone \> 20 mg (or equivalent) oral or intravenous daily for \> 14 days
* Prednisone \> 5 mg and =\< 20 mg (or equivalent) daily for \> 30 days
* Equivalent dose of methotrexate \> 15 mg weekly
* Note: Azathioprine is allowed. Daily glucocorticoid-replacement for conditions such as adrenal or pituitary insufficiency is allowed. Topical, inhaled or local steroid use in doses that are not considered to cause systemic effects are permitted. Steroids for pre-medication related to chemotherapy as per local standard of care are permitted.
* Live or attenuated vaccination within 3 months prior to first dose of study drug (e.g. Measles/Mumps/Rubella \[MMR\], Yellow Fever, Rotavirus, Smallpox, etc.) and after initiation of canakinumab treatment
* Use of erythropoietin stimulating agents (ESA) or growth factors within four weeks prior to the start of the study
* Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment and for up to 130 days after last dose of study drug. Basic contraception methods include:
* Total abstinence (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 are not acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
* Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository
* Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Prior to entry into this study, cisplatin-based chemotherapy, which may be toxic to the fetus, may be given. The time between the end of cisplatin-based chemotherapy and the start canakinumab/placebo treatment is variable, resulting in a variable need for continuation of highly effective contraception. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks prior to first dose of study drug. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form (ICF). PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Canakinumab, PROCEDURE: Chest Radiography, PROCEDURE: Echocardiography, DRUG: Placebo Administration, OTHER: Quality-of-Life Assessment
Clonal Cytopenia of Undetermined Significance, Myeloid and Monocytic Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
UT Southwestern
Venetoclax and Azacitidine for Treatment of Therapy Related or Secondary Myelodysplastic Syndrome
This phase II trial studies the effect of venetoclax and azacitidine in treating patients with therapy related or secondary myelodysplastic syndrome. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax in combination with azacitidine may work better in treating patients with therapy related or secondary myelodysplastic syndrome.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE2
NCT05379166
STU-2022-0513
Inclusion Criteria:
* Ability to understand and the willingness to sign a written informed consent document
* Age \>= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included
* Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
* Previously untreated therapy related myelodysplastic syndrome (t-MDS) with Revised International Prognostic Scoring System (IPSS-R) risk categories Intermediate, High or Very High (i.e., minimum IPSS-R score of 3.5) and presence of \< 20% bone marrow blasts per bone marrow biopsy/aspirate
* Patients with t-MDS which is defined as patients who have had prior anti-cancer therapy including chemotherapy and/or radiation therapy
* Aspartate aminotransferase (AST) \< 3.0 x upper limit of normal (ULN) x upper limit of normal (ULN; local laboratory)
* Alanine aminotransferase (ALT) \< 3.0 x ULN x ULN
* Total bilirubin =\< 2 x ULN (except for patients with known Gilbert's syndrome)
* Creatinine clearance \>= 30 mL/min OR serum creatinine \< 1.5 x the ULN
* White blood cell (WBC) count =\< 10,000/uL
* Note: Treatment with hydroxyurea is permitted to lower the WBC to reach this inclusion criterion. The WBC should be determined \>= 24 hours after the last dose of hydroxyurea. The last dose of hydroxyurea should not be administered =\< 3 days prior to the first dose of azacitidine
* Females of childbearing potential (FOCBP) must agree to adequate contraception (1 form of contraception or abstinence) from the screening visit until 30 days following the last dose of venetoclax. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* FOCBP are those who have not been surgically sterilized or have not been free from menses for \> 1 year without an alternative medical cause
* Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 90 days after the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study treatment
Exclusion Criteria:
* Participant has received prior therapy with a venetoclax or other BH3 mimetic. Note: Prior supportive care in form of transfusions or growth factors, etc., is not considered prior therapy. Supportive care should be discontinued \>= 14 days prior to the first dose of study drug. Subjects may continue oral corticosteroids for management of conditions other than MDS (e.g., asthma, rheumatoid arthritis) at a stable daily dose equivalent to =\< 10 mg prednisone during screening and study participation
* Subject has a diagnosis other than previously untreated de novo MDS with IPSS-R risk categories Intermediate, High or Very High, including:
* MDS with IPSS-R risk categories Very Low or Low (overall IPSS score \< 3)
* MDS evolving from a pre-existing myeloproliferative neoplasm (MPN)
* MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN
* Patients who are suitable for and willing to receive intensive chemotherapy or eligible to proceed to allogeneic stem cell transplantation without additional therapy
* Known history of testing positive for Human Immunodeficiency Virus (HIV) infections, Hepatitis B, or Hepatitis C. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
* Clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure
* Patients with uncontrolled infection will not be enrolled until infection is treated and under control
* Hypersensitivity to any study agent when administered alone. Any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
* Any psychiatric illness that prevents patient from informed consent process
* Pregnant of breastfeeding at the time of enrollment
* Subject has received allogeneic HSCT or solid organ transplantation
* Subject has a concurrent active malignancy requiring treatment or with an expected life expectancy less than 1 year with the exception of below. Any subject with a concurrent active malignancy will be reviewed by the PI for eligibility prior to enrollment
* Adequately treated in situ carcinoma of the cervix uteri
* Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
* Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy
* Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
* Ongoing systemic infection (viral, bacterial, or fungal)
* Acute pneumonia
* Febrile neutropenia
* Subject has received strong or moderate CYP3A inducers within 7 days prior to the first dose of study drug
* Subject has received strong or moderate CYP3A inhibitors within 7 days prior to the first dose of study drug
* Subject has consumed one or more of the following within 3 days prior to the first dose of study drug:
* Grapefruit or grapefruit products
* Seville oranges (including marmalade containing Seville oranges)
* Star fruit (carambola)
* Subject has a malabsorption syndrome or other condition that precludes an enteral route of administration
* Subject has history of a cardiovascular, endocrinologic, hepatic, immunologic metabolic, neurologic, psychiatric, pulmonary, renal disease, or any other condition that in the opinion of the investigator would adversely affect his/her participation in this study or interpretation of study results
* Subject has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug DRUG: Azacitidine, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, DRUG: Venetoclax
Secondary Myelodysplastic Syndrome, Therapy-Related Myelodysplastic Syndrome, Myeloid and Monocytic Leukemia
UT Southwestern
Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients
The purpose of this study is to evaluate if the combination of drugs, Lenalidomide and Luspatercept, will help improve the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome (MDS).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE1
NCT04539236
STU-2023-1130
Inclusion Criteria:
• Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Documented diagnosis of MDS according to World Health Organization (WHO) / French-American-British (FAB) classification that meets International Prognostic Scoring System Revised (IPSS-R) classification (Greenberg, 2012) of very low, low, or intermediate risk disease; intermediate patients must have a blast percentage \<5% to be enrolled.
• Subjects can be ESA-naïve, or refractory or intolerant to, or ineligible for, prior ESA treatment, as defined by any one of the following: * Refractory to prior ESA treatment - documentation of non-response or response that is no longer maintained to prior ESA-containing regimen, either as single agent or combination (eg, with G-CSF); ESA regimen must have been either: * recombinant human erythropoietin (rHu EPO) ≥ 40,000 IU/wk for at least 8 doses or equivalent; OR * darbepoetin alpha ≥ 200-500 μg Q1-3W for at least 4 doses or equivalent; * Intolerant to prior ESA treatment - documentation of discontinuation of prior ESAcontaining regimen, either as single agent or combination (eg, with G-CSF), at any time after introduction due to intolerance or an adverse event * ESA ineligible - Low chance of response to ESA based on endogenous serum erythropoietin level \> 200 U/L for subjects not previously treated with ESAs
• If previously treated with ESAs, agents must have been discontinued ≥ 4 weeks prior to date of C1D1.
• Requires RBC transfusions, as documented by the following criteria: * average transfusion requirement of ≥ 2 units/8 weeks of packed Red Blood Cells (pRBC)s preceding C1D1. * Hemoglobin levels at the time of or within 7 days prior to administration of a RBC transfusion must have been ≤ 10.0 g/dL for the transfusion to be counted towards meeting eligibility criteria. Red blood cell transfusions administered when Hgb levels were \> 10.0 g/dL and/or RBC transfusions administered for elective surgery will not qualify as a required transfusion for the purpose of meeting eligibility criteria.
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 (Appendix 1)
• Females of childbearing potential (FCBP), defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months), must: * Have two negative pregnancy tests (urine or serum) as verified by the Investigator prior to starting study therapy (unless the screening pregnancy test was done within 72 hours of C1D1). She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. * If sexually active, agree to use, and be able to comply with, highly effective contraception without interruption, 5 weeks prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks after discontinuation of study therapy.
• Male subjects must: * Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (for example, polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks following investigational product discontinuation, even if he has undergone a successful vasectomy.
• Subject must have a negative Coronavirus Disease of 2019 (COVID-19) test completed ≤7 days prior to administration of protocol therapy.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
Exclusion Criteria:
• Prior therapy with Lenalidomide.
• Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
• MDS associated with del 5q cytogenetic abnormality
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding * iron deficiency to be determined by serum ferritin ≤ 15 μg/L and additional testing if clinically indicated (eg, calculated transferrin saturation \[iron/total iron binding capacity ≤ 20%\] or bone marrow aspirate stain for iron).
• Prior allogeneic stem cell transplant
• Known history of diagnosis of AML
• Use of any of the following within 4 weeks prior to C1D1: * anticancer cytotoxic chemotherapeutic agent or treatment * other RBC hematopoietic growth factors (eg, Interleukin-3) * investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half-life prior to C1D1 or within 5 weeks, whichever is longer is excluded.
• Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment.
• Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 1 year. However, subjects with the following history/concurrent conditions involving in situ cancer (or similar) are allowed: * Basal or squamous cell carcinoma of the skin * Carcinoma in situ of the cervix * Carcinoma in situ of the breast * Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis (TNM) clinical staging system)
• Major surgery within 4 weeks prior to C1D1. Subjects must have completely recovered from any previous surgery prior to C1D1
• History of stroke, deep venous thrombosis (DVT), pulmonary or arterial embolism within 6 months prior to C1D1
• Pregnant or breastfeeding females
• Subject has any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that, in the opinion of the Investigator, would prevent the subject from participating in the study.
DRUG: Lenalidomide, DRUG: Luspatercept
Myelodysplastic Syndromes, Myeloid and Monocytic Leukemia
non-del(5q) MDS
UT Southwestern
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to 75 Years old
PHASE3
NCT04530565
STU-2021-0640
Inclusion Criteria:
* ELIGIBILITY CRITERIA FOR PRE-REGISTRATION (TO STEP 0)
* Patient must be \>= 18 and =\< 75 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3
* Patient must be newly diagnosed with B acute lymphoblastic leukemia (B-ALL) or is suspected to have acute lymphoblastic leukemia (ALL)
* Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin step 1 therapy while awaiting central laboratory eligibility confirmation
* NOTE: Bone marrow aspirate and/or peripheral blood specimen must be submitted to the ECOG-American College of Radiology Imaging Network (ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow aspirate is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, with recommendation that adequate circulating blasts are present (\> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to step 1 without waiting for central confirmation
* Patient must not have a diagnosis of BCR/ABL T-ALL
* Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of therapy (hydroxyurea and/or steroids of any kind) with the aim to reduce disease burden prior to study registration to Step 1 are eligible
* Patient must not have unstable epilepsy that requires treatment
* Patients with lymphoid blast crisis chronic myeloid leukemia (CML) are not eligible
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
* Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
* Total bilirubin =\< 3 mg/dL (patients with Gilbert's syndrome must have a total bilirubin =\< 5 mg/dL) (obtained =\< 28 days prior to step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X the institutional upper limit of normal (ULN) (obtained =\< 28 days prior to step 1 registration)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation) (obtained =\< 28 days prior to step 1 registration)
* Patients with acute organ dysfunction at step 1 registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to step 2 randomization if the eligibility criteria outlined is met
* Patients who presented with no evidence of acute organ dysfunction but during step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver enzymes. Step 2 randomization must be withheld until the eligibility criteria outline is met but no more than 14 days after concluding Arm A therapy
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment
* Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies are eligible
* Patient must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during step 1. The investigator must re-specify dasatinib or ponatinib prior to step 2 randomization and from then on patients must receive the pre-selected TKI only
* ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
* Patient must have completed at least 7 and no more than 21 days of protocol-treatment on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for any reason are not counted)
* NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI must be initiated prior to randomization
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional upper limit of normal (ULN)
* AST(SGOT) and ALT(SGPT) =\< 2 X the institutional upper limit of normal (ULN)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive.
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization
* Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated
* Patients must have resolved any serious infectious complications related to therapy
* Any significant medical complications related to therapy must have resolved
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
* Institution has received centralized MRD results confirming positive status
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional ULN
* Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =\< 2 X institutional upper limit of normal (ULN)
* Patients who presented with acute organ dysfunction must have an estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined
* Step 3 (Re-Induction): Patients must have resolved any serious infectious complications related to therapy
* Step 3 (Re-Induction): Any significant medical complications related to therapy must have resolved PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography Test, PROCEDURE: Electrocardiography, PROCEDURE: Lumbar Puncture, DRUG: Mesna, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Ponatinib Hydrochloride, DRUG: Prednisone, DRUG: Vincristine Sulfate
B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1, Leukemia, Other
UT Southwestern
Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia
This phase I trial identifies the best dose and clinical benefit of giving pemigatinib following standard induction chemotherapy in patients with newly diagnosed acute myeloid leukemia. Pemigatinib selectively inhibits FGFR (fibroblast growth factor receptor) activity, a receptor that may contribute to the growth of leukemia cells. The genetic changes responsible for activating the growth of leukemia cells can be unique to each patient and can change during the course of the disease. Chemotherapy drugs, such as cytarabine and daunorubicin work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE1
NCT04659616
STU-2023-0606
Inclusion Criteria:
* PRE-SCREENING INCLUSION CRITERIA: Ability to understand and the willingness to sign a written informed consent document
* PRE-SCREENING INCLUSION CRITERIA: Age \>= 18 years at time of informed consent. Both men and women of all races and ethnic groups will be included
* PRE-SCREENING INCLUSION CRITERIA: Participants must consent to a bone marrow aspirate/biopsy that will be collected prior to start of planned 7+3 induction therapy. Patients with known favorable risk AML (2022 European Leukemia Net \[ELN\] Guidelines) or FLT3 mutations should not be pre-screened. If the risk category is unknown, then it is okay to pre-screen patients for study. Adverse or intermediate risk needs to be confirmed prior to treatment with pemigatinib (during screening period) as outlined below
* TREATMENT INCLUSION CRITERIA: Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* TREATMENT INCLUSION CRITERIA: For both the dose-determining and dose-expansion cohort, study population is limited to: Newly diagnosed, morphologically documented AML, based on the World Health Organization (WHO) 2008 classification, with wild-type FLT3 and cytogenetics or mutations associated with intermediate or adverse prognostic risk per European Leukemia Net (ELN) guidelines. These include:
* t(9;11)(p21.3;q23.3); MLLT3-KMT2A
* Cytogenetic abnormalities not classified as favorable
* t(6;9)(p23;q34.1); DEK-NUP214
* t(v;11q23.3); KMT2A rearranged
* t(9;22)(q34.1;q11.2); BCR-ABL1
* inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1)
* -5 or del(5q); -7; -17/abn(17p)
* Complex karyotype - defined as three or more unrelated chromosome abnormalities in the absence of 1 of the WHO-designated recurring translocations or inversions, that is, t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23.3), t(6;9), inv(3) or t(3;3); AML with BCR-ABL1
* Monosomal karyotype - defined by the presence of 1 single monosomy (excluding loss of X or Y) in association with at least 1 additional monosomy or structural chromosome abnormality (excluding core-binding factor AML)
* Mutated RUNX1 (without favorable risk cytogenetics/mutations)
* Mutated BCOR (without favorable risk cytogenetics/mutations)
* Mutated EZH2 (without favorable risk cytogenetics/mutations)
* Mutated ASXL1 (without favorable risk cytogenetics/mutations)
* Mutated SF3B1 (without favorable risk cytogenetics/mutations)
* Mutated SRSF2 (without favorable risk cytogenetics/mutations)
* Mutated STAG2 (without favorable risk cytogenetics/mutations)
* Mutated U2AF1, (without favorable risk cytogenetics/mutations)
* Mutated ZRSR2 (without favorable risk cytogenetics/mutations)
* Mutated TP53 (mono- or biallelic) at a variant allele fraction of at least 10%
* TREATMENT INCLUSION CRITERIA: Serum creatinine clearance \>= 30 mL/min (as calculated by Cockcroft-Gault formula) (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Serum phosphate within institutional upper limit of normal (ULN) or can be corrected with supplementation/ phosphate binders to be within institutional ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Serum electrolytes within institutional ULN: potassium, calcium (total, or corrected for serum albumin in case of hypoalbuminemia) and magnesium. If outside of normal limits, participant will be eligible when electrolytes are corrected (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Total serum bilirubin =\< 3 x ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =\< 3 x ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Participants must consent to standard of care bone marrow aspirate/biopsies during treatment. Bone marrow biopsies will be obtained prior to study, on day 21 (+/- 3 days, if considered institutional standard of care), after recovery from induction therapy, and at the end of consolidation and/or prior to allogeneic stem cell transplant
* TREATMENT INCLUSION CRITERIA: Female participants of childbearing potential must agree to use effective contraception (2 forms of contraception or abstinence) from the screening visit until 6 months following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* TREATMENT INCLUSION CRITERIA: Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 3 months following the last dose of study treatment. The male participant must also refrain from sperm donation from the screening visit until 3 months following the last dose of study treatment
Exclusion Criteria:
* PRE-SCREENING EXCLUSION CRITERIA: Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype) per WHO classification
* PRE-SCREENING EXCLUSION CRITERIA: AML with FLT3 mutations that qualify for standard of care treatment with 7+3 and midostaurin (e.g. FLT3 ITD or TKD with allelic ratio \> 0.05)
* PRE-SCREENING EXCLUSION CRITERIA: Favorable risk AML: inv(16), t(8;21), NPM1 mutations without FLT3-ITD, or in-frame mutations (mono- or biallelic) affecting the basic leucine zipper region of CEBPA
* PRE-SCREENING EXCLUSION CRITERIA: Any cancer-directed therapy within 2 weeks prior to starting planned 7+3 induction regimen, with the exception of hydroxyurea, which is allowed to control white blood cell count, or empiric all-trans retinoic acid (ATRA) for suspected APL
* PRE-SCREENING EXCLUSION CRITERIA: Prior receipt of a selective FGFR inhibitor
* PRE-SCREENING EXCLUSION CRITERIA: Known liver disease
* PRE-SCREENING EXCLUSION CRITERIA: History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues
* Except for commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
* PRE-SCREENING EXCLUSION CRITERIA: History of hypovitaminosis D being actively treated with supraphysiologic doses (e.g., 50,000 IU/weekly) to replenish the deficiency. Supraphysiologic doses of vitamin D need to be discontinued prior to starting pemigatinib. Vitamin D supplements are allowed
* PRE-SCREENING EXCLUSION CRITERIA: Untreated human immunodeficiency virus (HIV) or active hepatitis C detectable by PCR, or chronic hepatitis B
* Individuals positive for hepatitis B core antibody who are receiving intravenous immunoglobulin (IVIg) are eligible if HepB PCR is negative
* PRE-SCREENING EXCLUSION CRITERIA: History of cerebrovascular accident or intracranial hemorrhage within 2 months of enrollment
* PRE-SCREENING EXCLUSION CRITERIA: Unwillingness to receive infusion of blood products
* PRE-SCREENING EXCLUSION CRITERIA: Inability to take oral medication
* PRE-SCREENING EXCLUSION CRITERIA: Gastrointestinal condition/disorders that may raise gastric and/or small intestinal pH that could interfere with absorption, metabolism, or excretion of pemigatinib
* PRE-SCREENING EXCLUSION CRITERIA: Known history and/or current evidence of ectopic mineralization/calcification, including (but not limited to): soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification
* PRE-SCREENING EXCLUSION CRITERIA: Concurrent active malignancy with expected survival of \< 1 year
* PRE-SCREENING EXCLUSION CRITERIA: Active central nervous system involvement with AML
* TREATMENT EXCLUSION CRITERIA: Clinically significant coagulation abnormality (e.g., disseminated intravascular coagulation) that is present on or by day 8 of induction therapy prior to starting pemigatinib
* TREATMENT EXCLUSION CRITERIA: Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of planned induction therapy, New York Heart Association class III or IV congestive heart failure, and uncontrolled arrhythmia (participants with pacemaker or with atrial fibrillation and well controlled heart rate are allowed). History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
* A screening QT interval by Fridericia's Correction Formula (QTcF) interval \> 480 ms will result in exclusion.
* For participants with an intraventricular conduction delay (QRS interval \> 120 ms), the JTc interval may be used in place of the QTc with approval from Sponsor-Investigator. The JTc must be =\< 340 ms if JTc is used in place of the QTc.
* TREATMENT EXCLUSION CRITERIA: Left ventricular ejection fraction (LVEF) by echocardiogram \< 45% prior to initiating pemigatinib
* TREATMENT EXCLUSION CRITERIA: Active infection that is not well-controlled by antibacterial or antiviral therapy
* TREATMENT EXCLUSION CRITERIA: Current use of prohibited medications including use of any potent CYP3A4 inducers within 14 days or five half-lives (whichever is longer) before the first dose of study drug.
* Use of CYP3A4 inhibitors should be avoided but, if medically necessary, is permitted with a dose reduction of study drug
* Use of moderate CYP3A4 inhibitors are permitted.
* Based on the low overall bioavailability of topical ketoconazole, there are no restrictions on topical ketoconazole
* TREATMENT EXCLUSION CRITERIA: Current use of prohibited medication
* TREATMENT EXCLUSION CRITERIA: Hypersensitivity to pemigatinib, or its excipients, when administered alone
* TREATMENT EXCLUSION CRITERIA: Current evidence of corneal disorder/keratopathy, including (but not limited to): bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc., as confirmed by ophthalmologic examination.
* TREATMENT EXCLUSION CRITERIA: Pregnancy or breastfeeding at the time of enrollment
* TREATMENT EXCLUSION CRITERIA: Any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the participant or compliance with the protocol
* TREATMENT EXCLUSION CRITERIA: Active central nervous system involvement with AML
* TREATMENT EXCLUSION CRITERIA: Patients with FLT mutations PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspirate, PROCEDURE: Bone Marrow Biopsy, DRUG: Cytarabine, DRUG: Daunorubicin, PROCEDURE: Electrocardiography, DRUG: Pemigatinib
Acute Myeloid Leukemia, Myeloid and Monocytic Leukemia
UT Southwestern
A Study of ASTX030 (Cedazuridine in Combination With Azacitidine) in MDS, CMML, or AML
Study ASTX030-01 is designed to move efficiently from Phase 1 to Phase 3. Phase 1 consists of an open-label Dose Escalation Stage (Stage A) using multiple cohorts at escalating dose levels of oral cedazuridine and azacitidine (only one study drug will be escalated at a time) followed by a Dose Expansion Stage (Stage B). Phase 2 is a randomized, open-label, crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 is a randomized open-label crossover study comparing the final oral ASTX030 dose to SC azacitidine. The duration of this phase 1-3 study is approximately 7 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE2
NCT04256317
STU-2023-0235
Inclusion Criteria:
Phase 2:
• Has Confirmed MDS, CMML, MDS/MPN or AML diagnosis who are candidates to receive and benefit from single agent azacitidine and as applicable according to local country approvals and/or local institution standard practice. Phase 3:
• Has confirmed MDS or CMML and is a candidate to receive and benefit from single agent azacitidine as applicable according to local country approvals and/or local institution standard practice: a) French-American-British myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and CMML or MDS with intermediate-2 or high risk MDS according to the International Prognostic Scoring System (IPSS).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Participants with adequate organ function.
• For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD).
• Participants with no major surgery within 3 weeks before first study treatment.
• Participants with no cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before first study treatment.
• Participants with projected life expectancy of at least 12 weeks.
Exclusion Criteria:
Phase 2 and 3:
• Has an active uncontrolled gastric or duodenal ulcer.
• Has poor medical risk because of other conditions.
• Has known human immunodeficiency virus (HIV) infection.
• Is known to be positive for Hepatitis B or C infection.
• Has a life-threatening illness.
• Has a history of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected or adequately treated and controlled with other modalities; and any early stage malignancy for which no definitive therapy is required.
• Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
• Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
• Has been treated with any investigational drug or therapy within 2 weeks, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events from previous treatment with investigational drug or therapy.
• Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
DRUG: Azacitidine, DRUG: ASTX030 (cedazuridine + azacitidine), DRUG: Azacitidine, DRUG: ASTX030 (cedazuridine + azacitidine), DRUG: Cedazuridine
Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myelodysplastic Syndrome/Neoplasm, Chronic Myelomonocytic Leukemia, Leukemia, Other, Myeloid and Monocytic Leukemia
ASTX030, Myeloid Neoplasm, Hematologic Disease, Leukemia, Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), Vidaza™, Azacitadine, Azacitadine and cedazuridine drug combination
UT Southwestern
Study of Biomarker-Based Treatment of Acute Myeloid Leukemia
This screening and multi-sub-study Phase 1b/2 trial will establish a method for genomic screening followed by assigning and accruing simultaneously to a multi-study "Master Protocol (BAML-16-001-M1)." The specific subtype of acute myeloid leukemia will determine which sub-study, within this protocol, a participant will be assigned to evaluate investigational therapies or combinations with the ultimate goal of advancing new targeted therapies for approval. The study also includes a marker negative sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
All
60 Years and over
Phase 1/Phase 2
NCT03013998
STU 012017-028
Inclusion Criteria:
• Adults, age 60 years or older at the time of diagnosis
• Subjects or their legal representative must be able to understand and provide written informed consent
• Cohort Inclusion Criteria - Group A: Subjects must have previously untreated acute myeloid leukemia (AML) according to the WHO classification with no prior treatment other than hydroxyurea. Prior therapy for myelodysplastic syndrome (MDS), myeloproliferative syndromes (MPD), or aplastic anemia is permitted but not with hypomethylating agents.
• Cohort Inclusion Criteria - Group B: Subjects must have relapsed or refractory AML according to the WHO classification. For study purposes, refractory AML is defined as failure to ever achieve CR or recurrence of AML within 6 months of achieving CR; relapsed AML is defined as all others with disease after prior remission. (Group B is not currently recruiting. Expected to begin recruiting in 3rd quarter 2017.)
Exclusion Criteria:
• Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML to enter the study)
• Acute promyelocytic leukemia
• Symptomatic central nervous system (CNS) involvement by AML
• Signs of leukostasis requiring urgent therapy
• Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis
• Patients with psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol, or potentially hamper compliance with study treatment and follow-up
• Any other significant medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient participating in the trial or would confound the interpretation of the results of the trial
Biological: Samalizumab (BAML-16-001-S1), Biological: BI 836858 (BAML-16-001-S2), Other: Laboratory Biomarker Analysis, Drug: Daunorubicin (BAML-16-001-S1), Drug: Cytarabine (BAML-16-001-S1), Drug: Azacitidine (BAML-16-001-S2), Drug: AG-221 (BAML-16-001-S3), Drug: Azacitidine (BAML-16-001-S3), Drug: Entospletinib (BAML-16-001-S4), Drug: Azacitidine (BAML-16-001-S4), Drug: Entospletinib (BAML-16-001-S5), Drug: Decitabine (BAML-16-001-S5), Drug: Entospletinib (BAML-16-001-S6), Drug: Azacitidine (BAML-16-001-S6), Drug: Daunorubicin (BAML-16-001-S6), Drug: Cytarabine (BAML-16-001-S6), Drug: Pevonedistat (BAML-16-001-S9), Drug: Azacitidine (BAML-16-001-S9)
Previously Untreated Acute Myeloid Leukemia, Leukemia, Other
UT Southwestern
Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)
The study will be an open-label, Phase 1b study of R289 to determine tolerability and preliminary efficacy in patients with LR MDS who are relapsed, refractory/resistant, intolerant, or have inadequate response to prior therapies such as erythropoietin (EPO), thrombopoietin (TPO), luspatercept, or hypomethylating agents (HMAs) for MDS.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
All
18 Years and over
Phase 1/Phase 2
NCT05308264
STU-2022-0561
Inclusion Criteria:
• Patient must be ≥ 18 years of age at the time of signing the informed consent.
• Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts.
• Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as TPOs, EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Patients with del (5q) must have failed prior lenalidomide therapy.
• Must meet at least one of the disease-related criteria for RBC transfusion, or platelet count within 8 weeks prior to initial administration of study treatment:
• Symptomatic anemia untransfused with hemoglobin < 9.0 g/dL within 8 weeks of registration or red blood cell (RBC) transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin <9.0 g/dL.
• Clinically relevant thrombocytopenia (platelet counts of <100 × 109/L in at least 2 blood counts prior to study treatment and transfusion dependence). All subjects must have documented marrow iron stain. If marrow iron stain is not available, the transferrin saturation must be >20% or a serum ferritin > 100ng/100mL
• Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.
• Must have adequate organ function, defined as:
• Hepatic function:
• aspartate amino transferase (AST) or alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN)
• total bilirubin ≤ 1.5 × ULN
• Renal function defined as creatinine clearance > 60 mL/min (using Cockcroft-Gault), or blood creatine < 1.5 mg/dL
Exclusion Criteria:
• Prior treatment for MDS (i.e., TPOs, EPOs, HMAs) concluded < 2 weeks, luspatercept < 3 weeks, prior to study treatment
• Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.
• MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
• Diagnosis of chronic myelomonocytic leukemia.
• History of uncontrolled seizures.
• Uncontrolled bacterial or viral infection (i.e., documented HIV, hepatitis B or hepatitis C).
• History of an active malignancy within the past 2 years prior to study entry, with the exception of:
• Adequately treated in situ carcinoma of the cervix uteri
• Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or
• Any other malignancy with a life expectancy of more than 2 years
• History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator's opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.
• Prior history of bone marrow transplantation.
• Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 480 milliseconds [msec]) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 1) using Fridericia's QT correction formula.
• History of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy (within 2 weeks of initiating study treatment), or the toxicity of the relevant prior treatment has not been resolved yet.
• Use of concomitant medications that prolong the QT/QTc interval during study treatment
• Use of concomitant medications that are strong CYP3A or CYP2B6 inhibitors or inducers during study treatment
Drug: R906289 Monosodium (R289 Na)
Low Risk Myelodysplastic Syndromes, Myeloid and Monocytic Leukemia
MDS, LR MDS, Myelodysplastic Syndromes, Hematology Oncology, Hem/ Onc
UT Southwestern