StudyFinder
Search Results
8 Study Matches
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, 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. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better than combination chemotherapy alone in treating patients with B-ALL. This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment). Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
365 Days to 31 Years old
Phase 3
NCT03914625
STU-2019-1128
Inclusion Criteria:
• All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
• Age at diagnosis:
• Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
• Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
• Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS).
• B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment).
• B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment).
• Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate;
• OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
• OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells;
• OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without Down syndrome.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted (diagnostic biopsy for B-LLy must be performed within 14 days prior to enrollment).
• 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:
• Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior history of transient myeloproliferative disease (TMD) are not considered to have had a prior malignancy. They would therefore be eligible whether or not the TMD was treated with cytarabine.
• With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731.
• For patients receiving steroid pretreatment, the following additional exclusion criteria apply:
• Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids.
• DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis.
• Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to the start of systemic protocol therapy.
• B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
• Patient must not have acute undifferentiated leukemia (AUL).
• Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment).
• Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment.
• Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular disease are eligible but will be assigned to the DS-High B-ALL arm).
• For LLy patients, the following additional exclusion criteria apply:
• T-Lymphoblastic Lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
• CNS positive disease or testicular involvement.
• M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• 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.
Drug: Asparaginase Erwinia chrysanthemi, Biological: Blinatumomab, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Mercaptopurine Oral Suspension, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Prednisone, Radiation: Radiation Therapy, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine Sulfate
B Acute Lymphoblastic Leukemia, Down Syndrome, B Lymphoblastic Lymphoma
Children’s Health
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
This is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as LOXO-292) administered orally to participants with advanced solid tumors, including rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
206021
All
12 Years and over
Phase 1/Phase 2
NCT03157128
STU 082018-008
Key
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Inclusion Criteria:
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Drug: LOXO-292
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib, neo-adjuvant treatment in early stage NSCLC
UT Southwestern
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
74989
All
12 Months to 21 Years old
Phase 2
NCT03155620
STU 072017-080
Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g. langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where patient enrolls prior to histologic confirmation of recurrent disease, patient is ineligible and should be withdrawn from study if histology fails to confirm recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting 2022): In stage 2 of the study, no tumor samples will be submitted for centralized clinical tumor profiling; instead, a tumor molecular profiling report from a College of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments (CLIA)-approved testing laboratory must be submitted for review by the Molecular Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was obtained at any point after initial tumor recurrence/progression and must be accompanied by a pathology report for the same tumor specimen; a molecular profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that molecular profiling reports are available from multiple timepoints, the most recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic deficits in patients with central nervous system (CNS) tumors must have been stable for at least 7 days prior to study enrollment; 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
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have radiographically measurable disease; measurable disease based on imaging obtained less than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; 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
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
• Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer 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 >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC]): >= 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
• 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
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells, etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation; note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: 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: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase (SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in females who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols
Procedure: Biopsy, Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration and Biopsy, Procedure: Bone Scan, Procedure: Computed Tomography, Drug: Ensartinib, Drug: Erdafitinib, Other: Laboratory Biomarker Analysis, Drug: Larotrectinib Sulfate, Procedure: Magnetic Resonance Imaging, Procedure: Mutation Carrier Screening, Drug: Olaparib, Drug: Palbociclib, Other: Pharmacological Study, Procedure: Positron Emission Tomography, Procedure: Radionuclide Imaging, Drug: Samotolisib, Drug: Selpercatinib, Drug: Selumetinib Sulfate, Drug: Tazemetostat, Drug: Tipifarnib, Drug: Ulixertinib, Drug: Vemurafenib, Procedure: X-Ray Imaging
Recurrent Childhood Rhabdomyosarcoma, Recurrent Neuroblastoma, Malignant Glioma, Recurrent Osteosarcoma, Recurrent Malignant Solid Neoplasm, Advanced Malignant Solid Neoplasm, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Wilms Tumor, Recurrent Glioma, Refractory Malignant Solid Neoplasm, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Histiocytic Sarcoma, Juvenile Xanthogranuloma, Recurrent Langerhans Cell Histiocytosis, Recurrent Peripheral Primitive Neuroectodermal Tumor, Refractory Langerhans Cell Histiocytosis, Refractory Neuroblastoma, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Refractory Non-Hodgkin Lymphoma, Recurrent Medulloblastoma, Recurrent Non-Hodgkin Lymphoma, Refractory Malignant Germ Cell Tumor, Langerhans Cell Histiocytosis, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Medulloblastoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Rhabdoid Tumor, Recurrent Malignant Germ Cell Tumor, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Rhabdomyosarcoma, Recurrent Ependymoma, Refractory Primary Central Nervous System Neoplasm, Recurrent Primary Central Nervous System Neoplasm
Children’s Health
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.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 21 Years old
Phase 2
NCT02981628
STU 062017-028
Inclusion Criteria:
• 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 if Erwinia formulation of asparaginase can be obtained
• 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
Drug: Asparaginase Erwinia chrysanthemi, Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration and Biopsy, Drug: Calaspargase Pegol, Drug: Cyclophosphamide, Drug: Cytarabine, Procedure: Diagnostic Imaging, Biological: Inotuzumab Ozogamicin, Drug: Leucovorin Calcium, Procedure: Lumbar Puncture, Drug: Methotrexate, Drug: Pegaspargase, Drug: Vincristine
Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma, Leukemia, Other
Children’s Health
A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051)
This is a two-part study of pembrolizumab (MK-3475) in pediatric participants who have any of the following types of cancer: - advanced melanoma (6 months to <18 years of age), - advanced, relapsed or refractory programmed death-ligand 1 (PD-L1)-positive malignant solid tumor or other lymphoma (6 months to <18 years of age), - relapsed or refractory classical Hodgkin lymphoma (rrcHL) (3 years to <18 years of age), or - advanced relapsed or refractory microsatellite-instability-high (MSI-H) solid tumors (6 months to <18 years of age). Part 1 will find the maximum tolerated dose (MTD)/maximum administered dose (MAD), confirm the dose, and find the recommended Phase 2 dose (RP2D) for pembrolizumab therapy. Part 2 will further evaluate the safety and efficacy at the pediatric RP2D. The primary hypothesis of this study is that intravenous (IV) administration of pembrolizumab to children with either advanced melanoma; a PD-L1 positive advanced, relapsed or refractory solid tumor or other lymphoma; advanced, relapsed or refractory MSI-H solid tumor; or rrcHL, will result in an Objective Response Rate (ORR) greater than 10% for at least one of these types of cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
128737
All
6 Months to 17 Years old
Phase 1/Phase 2
NCT02332668
STU 052016-090
Inclusion Criteria:
• Between 6 months and <18 years of age (or between 3 years and <18 years of age for rrcHL participants) on day of signing informed consent/assent (the first 3 participants dosed in Part 1 are to be ≥ 6 years of age)
• Histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
• Any number of prior treatment regimens
• Tissue (or lymph node biopsy for rrcHL participants) available from an archival tissue sample or, if appropriate, a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphoma
• Measurable disease based on RECIST 1.1 (Or based on IWG [Cheson, 2007] [i.e., measurement must be >15 mm in longest diameter or >10 mm in short axis] for rrcHL participants)
• Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
• Lansky Play Scale ≥50 for participants from 6 months up to and including 16 years of age; or Karnofsky score ≥50 for participants >16 years of age
• Adequate organ function
• Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication
• Female participants of childbearing potential must be willing to use 2 methods of contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
• Male participants of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication
Exclusion Criteria:
• Currently participating and receiving study therapy in, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the date of allocation/randomization
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the date of allocation/randomization
• Prior systemic anti-cancer therapy including investigational agent within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
• Prior radiotherapy within 2 weeks of start of study treatment
• Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical carcinoma in situ) with potentially curative therapy, or in situ cervical cancer
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Tumor(s) involving the brain stem
• Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
• Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Active infection requiring systemic therapy
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after the last dose of study medication
• Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand 1 (anti-PD-L1), anti-PD-L2 agent, or any agent directed to another stimulatory or inhibitory T-cell receptor (eg, cytotoxic lymphocyte associated protein-4 [CTLA-4], OX-40, CD137)
• Human immunodeficiency virus (HIV)
• Hepatitis B or C
• Known history of active tuberculosis (TB; Bacillus tuberculosis)
• Received a live vaccine within 30 days of planned start of study medication
• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had an allogeneic hematopoietic transplant >5 years ago are eligible as long as there are no symptoms of Graft Versus Host Disease [GVHD].)
• History or current evidence of any condition, therapy, or laboratory abnormality, or known severe hypersensitivity to any component or analog of the trial treatment, that might confound the results of the trial, or interfere with the participant's participation for the full duration of the study
• Known psychiatric or substance abuse disorders that would interfere with the requirements of the study
Biological: Pembrolizumab
Lymphoma, Melanoma, Classical Hodgkin Lymphoma, Solid Tumor, Microsatellite-instability-high Solid Tumor, Other, Melanoma, skin
PD1, PD-1, PDL1, PD-L1, cHL, MSI-H
Children’s Health
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.
Call 214-648-5005
studyfinder@utsouthwestern.edu, brittany.henderson@childrens.com
Victor Aquino
10208
All
Not specified
Phase 2
NCT01861093
STU 082013-056
• 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)
Procedure: Cord Blood Units
Leukemia, Lymphoma, Aplastic Anemia, Myelodysplastic Syndrome (MDS), Unknown Sites
Unrelated Hematopoietic Stem Cell Transplantation, Cryopreserved Cord Blood Units, National Cord Blood Program
Children’s Health
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The goal is to find the highest dose of MM-398 that can be given safely when it is used together with the chemotherapy drug Cyclophosphamide.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Patrick Leavey
35610
All
12 Months to 20 Years old
Phase 1
NCT02013336
STU 092013-007
Inclusion Criteria:
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Neuroblastoma, Sarcoma, Ewing Sarcoma, Mycosis Fungoides, Rhabdomyosarcoma, Osteosarcoma, Recurrent or Refractory Solid Tumors, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, 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, Hodgkins Lymphoma, Kaposis sarcoma, Other Hematopoietic, Small Intestine, Soft Tissue
pediatric, MM-398, cyclophosphamide, irinotecan
Children’s Health
PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
This is a phase 1/2 study of a drug called Ixazomib in combination with cytotoxic chemotherapy consisting of Vincristine, Dexamethasone, Asparaginase, and Doxorubicin (VXLD).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 21 Years old
Phase 1
NCT03817320
STU-2019-0546
Inclusion Criteria:
• Age Patients must be ≤21 years of age at the time of enrollment.
• Phase 1 - Initial enrollment will be restricted to patients < 18 years of age until 9 such patients are enrolled
• Phase 2 - Initial enrollment will be restricted to patients < 18 years of age until 6 such patients are enrolled
• Diagnosis Patients must have a diagnosis of relapsed/refractory ALL or LLy with or without extramedullary disease (including CNS2 and CNS3). Patient with mixed phenotype ALL or mature B (Burkitt-like) leukemia are not eligible.
• Patients with ALL must have ≥ 5% blasts by morphology.
• Patients with LLy must have measurable disease documented by clinical, radiologic or histologic criteria
• Performance Level Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age.
• Prior Therapy A. Prior therapeutic attempts
• Phase 1 - Any patients with relapsed/refractory ALL or LLy
• Phase 2
• B-cell ALL/LLy: all patients must have failed two or more therapeutic attempts.
• T-cell ALL/LLy: all patients must have failed one or more therapeutic attempts. B. Recent prior chemotherapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Cytoreduction with hydroxyurea Hydroxyurea can be initiated and continued for up to 24 hours prior to the start of protocol therapy.
• Patients who relapsed while they are receiving cytotoxic therapy At least 14 days must have elapsed since the completion of the last dose of chemotherapy,except Intrathecal chemotherapy, and/or maintenance therapy such as vincristine, mercaptopurine, methotrexate or glucocorticoids. There is no waiting period for those relapsing on maintenance therapy. C. Hematopoietic stem cell transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 90 days post-transplant at the time of enrollment. D. Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with G-CSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®). E. Biologic (anti-neoplastic agent): At least 7 days since the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair
• Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of monoclonal antibody. (i.e., blinatumomab = 6 hours,44 inotuzumab = 37 days, rituximab = 66 days)
• Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g., tumor vaccines, CAR T cells. F. XRT: Craniospinal XRT is prohibited during protocol therapy. No washout period is necessary for radiation given to any extramedullary site other than CNS; ≥90 days must have elapsed if prior total body irradiation (TBI) or craniospinal XRT. G. Anthracyclines: Patients must have had a lifetime exposure of <400 mg/m2 of doxorubicin equivalents of anthracyclines. H. Proteasome inhibitors: Patients with a prior exposure to proteasome inhibitors (e.g., bortezomib, carfilzomib) are eligible as long as the patient demonstrated at least a partial response to a proteasome inhibitor with chemotherapy combination. -Renal and hepatic function Patients must have adequate renal and hepatic functions as indicated by the following laboratory values: A. Adequate renal function defined as: Patient must have a calculated creatinine clearance or radioisotope GFR 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender B. Adequate Liver Function Defined as: Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) for age or normal (except in the presence of Gilbert's syndrome), AND alanine transaminase (ALT) ≤ 5 x ULN for age. The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia or lymphoma. This must be reviewed by and approved by the study chair or vice chair.
• Adequate Cardiac Function Defined as: Shortening fraction of more than or equal to 27% by echocardiogram, OR ejection fraction of equal to or more than 50% by radionuclide angiogram (MUGA).
• Reproductive Function A. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment. B. Female patients with infants must agree not to breastfeed their infants while on this study. C. Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.
• Informed Consent Patients and/or their parents or legal guardians must be capable of understanding the investigational nature, potential risks and benefits of the study. All patients and/or their parents or legal guardians must sign a written informed consent. Age appropriate assent will be obtained per institutional guidelines. To allow non-English speaking patients to participate in this study, bilingual health services will be provided in the appropriate language when feasible.
• All institutional, FDA, and OHRP requirements for human studies must be met.
Exclusion Criteria:
Patients will be excluded if they have isolated CNS or testicular disease.
Patients will be excluded if they have ≥grade 2 peripheral sensory or motor neuropathy
(defined by the Modified "Balis" Pediatric Scale of Pediatric Neuropathies) at the time of
enrollment (see section 4.7.1.1).
Patients will be excluded if they have a known allergy or intolerance to any of the drugs
used in the study - except for PEG-asparaginase for which erwinia asparaginase may be
substituted
Patients will be excluded if they have a systemic fungal, bacterial, viral or other
infection that is exhibiting ongoing signs/symptoms related to the infection without
improvement despite appropriate antibiotics or other treatment. The patient needs to be off
pressors and have negative blood cultures for 48 hours.
Patients will be excluded if there is a plan to administer non-protocol chemotherapy,
radiation therapy, or immunotherapy during the study period.
Patients will be excluded if they have significant concurrent disease, illness, psychiatric
disorder or social issue that would compromise patient safety or compliance with the
protocol treatment or procedures, interfere with consent, study participation, follow up,
or interpretation of study results.
Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are
excluded.
Patients will be excluded if they have had a lifetime exposure of ≥400 mg/m2 doxorubicin
equivolents of anthracyclines (anthracycline equivalence to doxorubicin conversion see
appendix iv) .
Concomitant medications Investigational drugs: Patients currently receiving another
investigational drug are not eligible.
Anti-GVHD agents post transplant: patients who are receiving cyclosporine, tacrolimus or
other agents to prevent graft-versus-host disease post hematopoetic stem cell transplant
are not eligible.
CYP3A4 agents: patients who are currently receiving drugs that are strong inducers of
CYP3A4 are not eligible. Strong inducers of CYP3A4 should be avoided from 14 days prior to
enrollment to the end of the study. See appendix ii for a list of agents which fall into
this category.
Patients with Ph+ALL and Ph-like ALL who are currently receiving TKI therapy
Infants or Patients with Down Syndrome will be excluded in phase 2 of the study
Drug: Ixazomib, Drug: Vincristine, Drug: Dexamethasone, Drug: Asparaginase, Drug: Doxorubicin
ALL, Childhood, Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Lymphoma, Childhood, Lymphoid Leukemia
Children’s Health