Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia

Running, not enrolling · Phase 2

Conditions studied: Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, Recurrent Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia

In brief

This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in treating older patients with acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as prednisone, vincristine sulfate, methotrexate, and mercaptopurine, 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. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab with combination chemotherapy or dasatinib and prednisone may kill more cancer cells.

Key facts

Study ID

NCT02143414

Run by

National Cancer Institute (NCI)

People needed

53

Starts

2015-06-30

Expected to finish

2027-06-06

Last updated by the study team

2026-08-04

Who can join

Age: 65 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Registration Step 1 - Induction/Re-Induction:
• Patients must have a new morphologic diagnosis of precursor B cell acute lymphoblastic leukemia (ALL) (non T cell) based on World Health Organization (WHO) criteria; patients with Burkitt's (L3) are excluded; patients with Ph-positive or Ph-like ALL with dasatinib-sensitive mutations or kinase fusions may have relapsed or refractory diagnoses
• NOTE: Relapsed/refractory Ph-positive patients or Ph-like patients with dasatinib-sensitive mutations or kinase fusions who have previous exposure to either dasatinib or another 2nd or 3rd generation tyrosine kinase inhibitor (TKI) will begin protocol therapy with Cohort 2: re-induction cycle 1
• Patients must have a diagnosis of Philadelphia chromosome negative ALL or Ph chromosome positive ALL by cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR); patients will be registered to receive treatment in either Cohort 1 (Ph-) or Cohort 2 (Ph+ or Ph-like DSMKF) based on these results; diagnostic specimens must be submitted to the site's local Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory and results of tests (cytogenetics, FISH or PCR) must confirm Ph status prior to registration; if not already known, breakpoint cluster region- abelson murine leukemia viral oncogene homolog 1 (BCR-ABL) status (p190 or p210) must be evaluated in Ph-positive patients by PCR
• For Cohort 2, Ph-like testing is not required specifically for this study; however, to be registered to Cohort 2 under the Ph-like DSMKF criterion, the patient must have a known or presumed activating Ph-like signature and dasatinib-sensitive mutation or kinase fusion, such as: ABL1, ABL2, colony stimulating factor 1 receptor (CSF1R), platelet derived growth factor receptor beta (PDGFRB), platelet derived growth factor receptor alpha (PDGFRA), or fibroblast growth factor receptor (FGFR)s that was otherwise identified as part of normal standard of care; prior to registering any patients with a known or presumed activating Ph-like signature and dasatinib-sensitive mutations or kinase fusions (DSMKF) treating physicians must confirm eligibility with the study chairs via email; the study chairs must respond via email with confirmation of patient eligibility prior to patient registration
• All newly diagnosed patients must have evidence of ALL in their marrow or peripheral blood with at least 20% lymphoblasts present in blood or bone marrow collected within 28 days prior to registration; all relapsed/refractory patients (Cohort 2) must have at least 5% lymphoblasts present in blood or bone marrow collected within 28 days prior to registration; for relapsed/refractory patients, pathology and cytogenetics reports (both from time of original diagnosis) must be submitted at time of registration; if a bone marrow aspirate cannot be obtained despite an attempt (dry tap), appropriate immunohistochemistry (IHC) testing, including cluster of differentiation (CD)19, must be performed on the bone marrow biopsy to determine lineage; for ALL in marrow or peripheral blood, immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T cell or mixed B/T cell); appropriate marker studies including CD19 (B cell), must be performed; co-expression of myeloid antigens (CD13 and CD33) will not exclude patients; if possible, the lineage specific markers (myeloid cells) should be determined; the blood/bone marrow sample for these assays must be obtained within 28 days prior to registration; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible
• Patient must not have a history or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, active ALL in the CNS confirmed by cerebrospinal fluid (CSF) analysis, or other significant CNS abnormalities
• Patients must have a lumbar puncture to determine CNS involvement of ALL within 14 days prior to registration; patients with CNS3 are excluded from the trial; patients with CNS1 or CNS2 will be eligible, but will be monitored for CNS involvement; note that intrathecal methotrexate administered during the pre-study lumbar puncture may count as the first dose of intrathecal therapy required as part of the study
• Cohort I, Ph-negative Patients Only: Patients must not have received any prior chemotherapy, radiation therapy, or other therapy for the treatment of ALL (other than those noted below) and must not be receiving any immunosuppressive therapy; patients may not have received any prior investigational therapy within 28 days prior to registration; patients must not have received any monoclonal antibody therapy within 42 days of registration; patients may have received the following within any time prior to registration: low dose chemotherapy-including: cyclophosphamide 1 g/m\^2, oral 6-mercaptopurine, or oral methotrexate (other low dose chemotherapy may be allowable, however any other options not listed here should be confirmed with the study chairs), TKI therapy, steroids, hydroxyurea, leukapheresis, intrathecal chemotherapy or vincristine
• Cohort I, Ph-negative Patients Only: In the event that the patient's bone marrow blast count is >= 50% blasts, patients may be registered but should receive steroids for 3-5 days in order to reduce tumor burden prior to blinatumomab administration, as follows
• Prephase treatment with dexamethasone (10-20 mg/m\^2) for 3-5 days is required for patients with bone marrow blasts >= 50%, peripheral blood blasts 15,000/uL or higher, or elevated lactate dehydrogenase (LDH) suggesting rapidly progressive disease per investigator opinion
• Pre-treatment should conclude at least 24 hours prior to the first dose of blinatumomab (although additional dexamethasone is automatically given as a pre-med prior to the first dose); at the time of first infusion of blinatumomab, the absolute peripheral blast count should be < 25,000/uL
• Note: For the purposes of the study, day 1 of the cycle will be the first day of blinatumomab administration
• Cohort I, Ph-negative Patients Only: It is preferred, but not required, that corticosteroids and hydroxyurea should start only after all diagnostic samples have been obtained; however, if the patient was previously on corticosteroids and/or hydroxyurea, this is allowable provided that the patient still has measurable disease at time of the bone marrow aspirate
• Corticosteroids and/or hydroxyurea, as well as any of the other therapies mentioned (with the exception of IV cyclophosphamide), may continue to be administered, at physician discretion, until 1 day prior to blinatumomab administration
• IV cyclophosphamide must be discontinued at least 7 days prior to blinatumomab administration
• Cohort 2, Ph-positive and Ph-like DSMKF Patients Only: Patients must NOT have received a prior autologous or allogeneic hematopoietic stem cell transplant at any time. Patients must NOT have received any chemotherapy, investigational agents, or undergone major surgery within 14 days prior to registration, with the following exceptions:
• Monoclonal antibodies must not have been received for 1 week prior to registration
• Chimeric antigen receptor (CAR) T-cells must not have been received for 28 days prior to registration
• Steroids, hydroxyurea, vincristine, 6-mercaptopurine, methotrexate, thioguanine and intrathecal chemotherapy are permitted within any timeframe prior to registration; Food and Drug Administration (FDA)-approved TKIs may also be administered until 1 day prior to start of study therapy (C1, D1); IV cyclophosphamide may be administered at doses of 1 g/m\^2 or less until up to 7 days prior to registration
• Patients must be >= 65 years of age; for patients 65-69 years of age, patient must be deemed not suitable for standard intensive induction chemotherapy at the discretion of the local investigator, or must have refused standard intensive chemotherapy
• Cohort I, Ph-negative Patients Only: Patients must not be candidates for allogeneic hematopoietic stem cell transplant; NOTE: Subjects up to age 70 years who are considered fit for allogeneic hematopoietic stem cell transplant, should be considered for enrollment on E1910, in order to avoid competing with that study; if a patient is considered unfit for intensive chemotherapy at the time of initial diagnosis, but subsequently achieves a complete remission (CR), then it will be left to the treating physician's discretion to consider hematopoietic stem cell transplant (HSCT)
• Cohort I, Ph-negative Patients Only: Patients must have complete history and physical examination within 28 days prior to registration
• Cohort I, Ph-negative Patients Only: Patients must have a Zubrod performance status of 0-2
• Cohort I, Ph-negative Patients Only: Patients must have serum creatinine =< 1.5 mg/dl within 14 days prior to registration

Where it is running

• Banner University Medical Center - Tucson — Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States
• John L McClellan Memorial Veterans Hospital — Little Rock, Arkansas, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• UC San Diego Moores Cancer Center — La Jolla, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Los Angeles General Medical Center — Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• USC Norris Oncology/Hematology-Newport Beach — Newport Beach, California, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States
• Keck Medical Center of USC Pasadena — Pasadena, California, United States
• Smilow Cancer Center/Yale-New Haven Hospital — New Haven, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Orlando Health Cancer Institute — Orlando, Florida, United States
• Northside Hospital — Atlanta, Georgia, United States
• Augusta University Medical Center — Augusta, Georgia, United States
• Rush-Copley Medical Center — Aurora, Illinois, United States
• OSF Saint Joseph Medical Center — Bloomington, Illinois, United States
• Illinois CancerCare-Bloomington — Bloomington, Illinois, United States
• Illinois CancerCare-Canton — Canton, Illinois, United States
• Memorial Hospital of Carbondale — Carbondale, Illinois, United States
• Illinois CancerCare-Carthage — Carthage, Illinois, United States
• Centralia Oncology Clinic — Centralia, Illinois, United States
• University of Illinois — Chicago, Illinois, United States
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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