Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia
- Conditions
- Acute Lymphoblastic LeukemiaB Acute Lymphoblastic LeukemiaB Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1Recurrent Acute Lymphoblastic LeukemiaRefractory Acute Lymphoblastic Leukemia
- Interventions
- Procedure: Biopsy ProcedureProcedure: Biospecimen CollectionProcedure: Bone Marrow Aspiration and BiopsyProcedure: Computed TomographyProcedure: Echocardiography TestProcedure: Lumbar PunctureProcedure: Magnetic Resonance ImagingProcedure: X-Ray Imaging
- Registration Number
- NCT02143414
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
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.
- Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the 3-year survival rate in elderly patients with newly diagnosed Philadelphia (Ph)-negative acute lymphoblastic leukemia (ALL) treated with blinatumomab followed by POMP (prednisone, vincristine sulfate, methotrexate, and mercaptopurine) maintenance.
II. To evaluate in a preliminary manner (feasibility study) the safety of dasatinib-steroid based induction followed by blinatumomab treatment in combination with dasatinib followed by dasatinib-based maintenance in patients with newly diagnosed Ph-positive ALL, relapsed/refractory Ph-positive ALL, and Ph-like dasatinib-sensitive mutations or kinase fusions (DSMKF) ALL (newly-diagnosed relapsed or refractory).
SECONDARY OBJECTIVES:
I. To evaluate toxicities in these patient populations treated with these regimens.
II. To estimate the rates of complete response (CR), complete remission with incomplete count recovery (CRi) and disease-free survival in Ph-negative patients.
III. To estimate disease-free and overall survival in Ph-positive ALL and Ph-like DSMKF ALL.
IV. To estimate in each cohort the rate of minimal residual disease (MRD) negativity, and the time to achieve MRD negativity (exploratory analysis).
V. To determine whether anti-idiotype antibodies directed against blinatumomab develop with blinatumomab treatment in this study.
ADDITIONAL TRANSLATIONAL MEDICINE OBJECTIVES:
I. To estimate the incidence of the Ph-like signature in elderly patients (\>= 65 years of age) with newly diagnosed Philadelphia-chromosome negative ALL.
II. To estimate the incidence of the various tyrosine-kinase fusions, making up the Ph-like signature in elderly patients with newly diagnosed Philadelphia-chromosome negative ALL.
III. To evaluate outcomes (event free survival \[EFS\] and overall survival \[OS\]) in patients with the Ph-like signature versus those without the Ph-like signature in Ph-negative ALL.
IV. To describe via single cell transcriptomics the clonal diversity in gene expression of participants on the trial.
V. To describe the methylation status of the overall genome as well as key driver genes of all participants in the trial.
OUTLINE: Patients are assigned to 1 of 2 treatment cohorts according to Philadelphia chromosome status.
COHORT I (PHILADELPHIA CHROMOSOME NEGATIVE PATIENTS):
INDUCTION: Patients receive blinatumomab intravenously (IV) continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and echocardiography (ECHO) during screening and a computed tomography (CT) scan and/or magnetic resonance imaging (MRI) as well as blood sample collection and bone marrow aspiration and biopsy throughout the trial. Patients undergo a lumbar puncture during screening and on study. Patients may also undergo a biopsy during screening. (Closed to accrual 06/29/17)
RE-INDUCTION: Patients not achieving CR or CRi after Induction, receive blinatumomab IV continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and ECHO during screening and a CT scan and/or MRI as well as blood sample collection and bone marrow aspiration and biopsy throughout the trial. Patients undergo a lumbar puncture during screening and on study. Patients may also undergo a biopsy during screening.
POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, lumbar puncture, and bone marrow aspiration and biopsy on study.
MAINTENANCE: Patients receive prednisone orally (PO) on days 1-5, vincristine sulfate IV on day 1, mercaptopurine PO on days 1-28, and methotrexate PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo a lumbar puncture and bone marrow aspiration and biopsy on study.
COHORT II (PHILADELPHIA CHROMOSOME POSITIVE PATIENTS):
INDUCTION: Patients receive dasatinib PO on days 1-84 and prednisone PO on days 1-24 with tapering on days 25-32 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and ECHO during screening and a CT scan and/or MRI throughout the trial. Patients undergo a lumbar puncture and bone marrow aspiration and biopsy during screening and on study. Patients may also undergo a biopsy during screening.
RE-INDUCTION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, a lumbar puncture, and bone marrow aspiration and biopsy on study.
POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28 and dasatinib PO on days 1-42. Treatment repeats every 42 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, lumbar puncture, and bone marrow aspiration and biopsy on study.
MAINTENANCE: Patients receive dasatinib PO on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive prednisone PO on days 1-5. Treatment repeats every 28 days for 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI as well as a lumbar puncture and bone marrow aspiration and biopsy on study.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually until 10 years from initial registration.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 53
-
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
-
Cohort I, Ph-negative Patients Only: Patients must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (IULN) within 14 days prior to registration
-
Cohort I, Ph-negative Patients Only: Patients must have total bilirubin =< 2.0 x IULN within 14 days prior to registration
-
Cohort I, Ph-negative Patients Only: Patients must have alkaline phosphatase =< 2.5 x IULN within 14 days prior to registration
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Cohort I, Ph-negative Patients Only: Patients must not have systemic fungal, bacterial, viral or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
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Cohort I, Ph-negative Patients Only: Patients must not have Common Terminology Criteria for Adverse Events (CTCAE) >= grade 2 neuropathy (cranial, motor or sensory) within 14 days prior to registration
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Cohort I, Ph-negative Patients Only: Patients known to be positive for HIV (the human immunodeficiency virus) may be eligible, providing they meet the following additional criteria within 28 days prior to registration:
- No history of acquired immune deficiency syndrome (AIDS)-defining conditions
- CD4 cells > 350 cells/mm^3
- If on antiretroviral agents, must not include zidovudine or stavudine
- Viral load =< 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or =< 25,000 copies HIV mRNA/mm^3 if not on cART
- Highly active antiretroviral therapy (HAART) regimens are acceptable providing they have only weak P450A4 interactions
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Cohort I, Ph-negative Patients Only: Patients must not have any known autoimmune disease
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Cohort I, Ph-negative Patients Only: Patients must not have testicular involvement; if clinical or ultrasound findings are equivocal, biopsy must be performed; all tests for establishing testicular involvement must be completed within 14 days prior to registration
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Cohort I, Ph-negative Patients Only: Patients with evidence of extramedullary disease at diagnosis will have computed tomography (CT) scan or magnetic resonance imaging (MRI) of the chest, abdomen and pelvis to obtain baseline values within 28 days prior to registration
-
Cohort I, Ph-negative Patients Only: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
-
Cohort I, Ph-negative Patients Only: Patients must have the following tests within 28 days prior to registration to obtain baseline measurements:
- Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR)/fibrinogen (all patients)
- Cohort 1, Ph- Patients Only: Neurologic assessment
-
Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must not have active pericardial effusion, ascites or pleural effusion of any grade based on chest x-ray and echocardiogram within 28 days prior to registration; exception: if the effusion is suspected to be related to the leukemia, the patient may have pericardial effusion =< grade 2 or pleural effusion =< grade 1
-
Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must have ejection fraction >= 45% based on echocardiogram performed within 28 days prior to registration
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Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must have QTcF (by Fridericia calculation) < 480/msec based on electrocardiogram (EKG) performed within 28 days prior to registration
-
Cohort 2, Ph+ and Ph-like DSMKF Patients Only: Patients must not be receiving any proton pump inhibitors at the time of registration
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Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to the site's preferred CLIA-approved cytogenetics laboratory; BCR-ABL status must be verified in Ph-positive patients by FISH, cytogenetics, and/or PCR prior to enrollment; if a patient is Ph-positive, PCR for both p190 and p210 must be sent
-
Patients must be offered participation in specimen submission for future research; with patient's consent, specimens must be submitted as outlined
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Cohort 1, Ph-negative Patients Only: Patients must have specimens submitted for blinatumomab immunogenicity assessment; collection of pretreatment specimens must be completed within 28 days prior to registration to S1318; specimens must be submitted to LabConnect
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Cohort 2, Ph-positive and Ph-like DSMKF Patients Only: Patients must agree to have specimens submitted for blinatumomab immunogenicity testing if subsequently moved to a blinatumomab containing treatment regimen on protocol
-
Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
-
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
-
Registration Step 2 - Post-Remission Therapy:
-
Cohort 1, Ph-negative Patients Only: Patients must have achieved CR or CRi within 2 cycles of induction/re-induction with blinatumomab
- NOTE: day 1 of post-remission = day 43 of the preceding cycle (+/- 3 days)
-
Cohort 2, Ph-positive and Ph-like DSMKF Patients Only: Newly diagnosed Ph+, newly-diagnosed Ph-like DSMKF, and relapsed/refractory Ph+ patients without prior dasatinib or other 2nd or 3rd generation TKI therapy, must have achieved CR or CRi within 1 cycle of induction with dasatinib/prednisone, or within 2 cycles of re-induction with blinatumomab; relapsed/refractory Ph+ or Ph-like DSMKF patients with prior dasatinib or other 2nd or 3rd generation TKI therapy must have achieved CR or CRi within 2 cycles of re-induction therapy with blinatumomab
- NOTE: day 1 of post-remission = day 85 of the preceding induction cycle (+/- 3 days), or day 43 of the preceding re-induction cycle (+/- 3 days) as applicable
-
Serum creatinine =< 1.5 mg/dl within 14 days prior to registration
-
AST and ALT =< 3.0 x institutional upper limit of normal (IULN) within 14 days prior to registration
-
Total bilirubin =< 2.0 x IULN within 14 days prior to registration
-
Absolute neutrophil count (ANC) >= 750/mcL within 28 days prior to registration
-
Platelets >= 50,000/mcL within 28 days prior to registration
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Patients must be registered to Step 2 within 28 days after count recovery; (Note: there is no maximum allotted time period for count recovery, providing patient remains in CR or CRi)
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All non-hematologic treatment related toxicities that are deemed clinically significant by the treating investigator must have resolved to =< grade 2
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Registration Step 3 - Maintenance: Patients must have documented CR or CRi within 28 days prior to registration; note that bone marrow examination is only required if there are clinical signs/symptoms of progression; if progression is a concern due to the length of the time for count recovery, a bone marrow examination is recommended
-
Registration Step 3 - Maintenance: Patients must have serum creatinine =< 1.5 mg/dl within 14 days prior to registration
-
Registration Step 3 - Maintenance: Patients must have AST and ALT =< 3.0 x institutional upper limit of normal (IULN) within 14 days prior to registration
-
Registration Step 3 - Maintenance: Patients must have total bilirubin < 2.0 x institutional upper limit of normal (IULN) within 14 days prior to registration
-
Registration Step 3 - Maintenance: Patients must have adequate marrow function as evidenced by ANC >= 750/mcL within 28 days prior to registration
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Registration Step 3 - Maintenance: Patients must have adequate marrow function as evidenced by platelets >= 75,000/mcL within 28 days prior to registration
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Registration Step 3 - Maintenance: All non-hematologic treatment related toxicities that are deemed clinically significant by the treating investigator must have resolved to =< grade 2
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort I (blinatumomab, POMP) Biopsy Procedure See Detailed Description Cohort I (blinatumomab, POMP) Biospecimen Collection See Detailed Description Cohort I (blinatumomab, POMP) Computed Tomography See Detailed Description Cohort I (blinatumomab, POMP) Echocardiography Test See Detailed Description Cohort I (blinatumomab, POMP) Mercaptopurine See Detailed Description Cohort I (blinatumomab, POMP) Blinatumomab See Detailed Description Cohort I (blinatumomab, POMP) Bone Marrow Aspiration and Biopsy See Detailed Description Cohort I (blinatumomab, POMP) Lumbar Puncture See Detailed Description Cohort I (blinatumomab, POMP) Magnetic Resonance Imaging See Detailed Description Cohort I (blinatumomab, POMP) Methotrexate See Detailed Description Cohort I (blinatumomab, POMP) Methotrexate Sodium See Detailed Description Cohort I (blinatumomab, POMP) Prednisone See Detailed Description Cohort I (blinatumomab, POMP) Vincristine See Detailed Description Cohort I (blinatumomab, POMP) Vincristine Sulfate See Detailed Description Cohort I (blinatumomab, POMP) X-Ray Imaging See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Biopsy Procedure See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Biospecimen Collection See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Blinatumomab See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Bone Marrow Aspiration and Biopsy See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Computed Tomography See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Dasatinib See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Echocardiography Test See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Lumbar Puncture See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Magnetic Resonance Imaging See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) X-Ray Imaging See Detailed Description Cohort II (dasatinib, prednisone, blinatumomab) Prednisone See Detailed Description
- Primary Outcome Measures
Name Time Method Overall Survival Rate (Cohort I) From the day of registration on study until death from any cause, assessed at 3 years To evaluate the 3-year overall survival rate in elderly participants with newly diagnosed Ph-negative ALL treated with blinatumomab followed by POMP maintenance. Overall
Incidence of Dose-limiting Toxicity (Cohort II) Up to day 42 of post-remission therapy Defined as any grade 4 or higher treatment-related, non-hematologic toxicity in the first cycle of post-remission therapy (blinatumomab/dasatinib) graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Only participants with Ph-positive ALL or Ph-like DSMKF ALL were evaluated.
- Secondary Outcome Measures
Name Time Method Number of Participants With Grade 3 Through 5 Adverse Events That Are Related to Study Drugs Duration of treatment and follow up until death or date of primary analysis (about 7.5 years) Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported by given type of adverse event. Adverse Events reported using CTCAE v 4.0, whereas Serious Adverse Events were reported with CTCAE v 5.0.
Overall Survival (Cohort II) Up to 10 years Estimated using the method of Kaplan-Meier.
Complete Response Rate (Cohort I) Participants are assessed after induction treatment and again after re-induction treatment, if re-induction treatment is received (i.e. up to 85 days after registration) Complete response rate is measured by the number of participants achieving complete remission (CR) or complete remission with incomplete platelet recovery (CRi) rate. CR is defined as having \<5% marrow aspirate blasts, ANC \>1,000/mcL, platelets \> 100,000/mcL, no blasts in peripheral blood, and C1 extramedullary disease status. CRi is the same as CR but platelet count may be \<= 100,000/mcL and/or ANC \<=1,000/mcL.
Disease-free Survival (Cohort II) Duration of treatment and follow up until death or date of primary analysis (about 7.5 years) An estimate of disease free survival in Ph-positive ALL and Ph-like DSMKF ALL (Cohort II). Disease free survival is measured by the number of years between the date the patient first achieves complete remission (CR) or complete remission with incomplete platelet recovery (CRi) until relapse from CR/CRi or death from any cause. CR is defined as having \<5% marrow aspirate blasts, ANC \>1,000/mcL, platelets \> 100,000/mcL, no blasts in peripheral blood, and C1 extramedullary disease status. CRi is the same as CR but platelet count may be \<= 100,000/mcL and/or ANC \<=1,000/mcL.
Minimal Residual Disease Negativity Participants are assessed after induction treatment and again after re-induction treatment, if re-induction treatment is received (i.e. up to 85 days after registration) To estimate in each cohort the rate of minimal residual disease (MRD) negativity.
Time to Achieve Minimal Residual Disease Negativity Up to 10 years Will be examined separately in descriptive analyses within each cohort.
Anti-idiotype Antibody Development Up to 10 years To determine whether anti-idiotype antibodies directed against blinatumomab develop with blinatumomab treatment in this study.
Trial Locations
- Locations (196)
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
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 Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
SSM Health Good Samaritan
🇺🇸Mount Vernon, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
🇺🇸New Lenox, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Radiation Oncology of Northern Illinois
🇺🇸Ottawa, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
OSF Saint Francis Radiation Oncology at Pekin
🇺🇸Pekin, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Valley Radiation Oncology
🇺🇸Peru, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Central Illinois Hematology Oncology Center
🇺🇸Springfield, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Springfield Memorial Hospital
🇺🇸Springfield, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
The Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
Franciscan Health Indianapolis
🇺🇸Indianapolis, Indiana, United States
Franciscan Saint Anthony Health-Michigan City
🇺🇸Michigan City, Indiana, United States
Woodland Cancer Care Center
🇺🇸Michigan City, Indiana, United States
Reid Health
🇺🇸Richmond, Indiana, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
McFarland Clinic - Boone
🇺🇸Boone, Iowa, United States
McFarland Clinic - Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
McFarland Clinic - Jefferson
🇺🇸Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
🇺🇸Marshalltown, Iowa, United States
Siouxland Regional Cancer Center
🇺🇸Sioux City, Iowa, United States
Cancer Center of Kansas - Chanute
🇺🇸Chanute, Kansas, United States
Cancer Center of Kansas - Dodge City
🇺🇸Dodge City, Kansas, United States
Cancer Center of Kansas - El Dorado
🇺🇸El Dorado, Kansas, United States
Cancer Center of Kansas - Fort Scott
🇺🇸Fort Scott, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
Cancer Center of Kansas-Kingman
🇺🇸Kingman, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Cancer Center of Kansas-Liberal
🇺🇸Liberal, Kansas, United States
Cancer Center of Kansas - McPherson
🇺🇸McPherson, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸Newton, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸Parsons, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸Pratt, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸Salina, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸Wellington, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
🇺🇸Westwood, Kansas, United States
Associates In Womens Health
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Ascension Via Christi Hospitals Wichita
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Wichita
🇺🇸Wichita, Kansas, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸Winfield, Kansas, United States
Oncology Hematology Care Inc-Crestview
🇺🇸Crestview Hills, Kentucky, United States
LSU Health Sciences Center at Shreveport
🇺🇸Shreveport, Louisiana, United States
University of Maryland/Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Hickman Cancer Center
🇺🇸Adrian, Michigan, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Weisberg Cancer Treatment Center
🇺🇸Farmington Hills, Michigan, United States
Corewell Health Farmington Hills Hospital
🇺🇸Farmington Hills, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
William Beaumont Hospital-Grosse Pointe
🇺🇸Grosse Pointe, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Ascension Borgess Hospital
🇺🇸Kalamazoo, Michigan, United States
Toledo Clinic Cancer Centers-Monroe
🇺🇸Monroe, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Niles Hospital
🇺🇸Niles, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Corewell Health William Beaumont University Hospital
🇺🇸Royal Oak, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
🇺🇸Saint Joseph, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Corewell Health Beaumont Troy Hospital
🇺🇸Troy, Michigan, United States
Sanford Joe Lueken Cancer Center
🇺🇸Bemidji, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Central Care Cancer Center - Bolivar
🇺🇸Bolivar, Missouri, United States
Parkland Health Center-Bonne Terre
🇺🇸Bonne Terre, Missouri, United States
Cox Cancer Center Branson
🇺🇸Branson, Missouri, United States
Mercy Cancer Center - Cape Girardeau
🇺🇸Cape Girardeau, Missouri, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
MU Health Care Goldschmidt Cancer Center
🇺🇸Jefferson City, Missouri, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
Mercy Hospital Joplin
🇺🇸Joplin, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Phelps Health Delbert Day Cancer Institute
🇺🇸Rolla, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Nebraska Medicine-Bellevue
🇺🇸Bellevue, Nebraska, United States
Nebraska Medicine-Village Pointe
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Northwell Health/Center for Advanced Medicine
🇺🇸Lake Success, New York, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
ECU Health Oncology Kenansville
🇺🇸Kenansville, North Carolina, United States
ECU Health Oncology Kinston
🇺🇸Kinston, North Carolina, United States
ECU Health Oncology Richlands
🇺🇸Richlands, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Miami Valley Hospital South
🇺🇸Centerville, Ohio, United States
Oncology Hematology Care Inc-Eden Park
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Mercy West
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Anderson
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Kenwood
🇺🇸Cincinnati, Ohio, United States
Oncology Hematology Care Inc-Blue Ash
🇺🇸Cincinnati, Ohio, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸Dayton, Ohio, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Oncology Hematology Care Inc-Healthplex
🇺🇸Fairfield, Ohio, United States
Blanchard Valley Hospital
🇺🇸Findlay, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Wayne Hospital
🇺🇸Greenville, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Toledo Clinic Cancer Centers-Maumee
🇺🇸Maumee, Ohio, United States
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
🇺🇸Maumee, Ohio, United States
Saint Charles Hospital
🇺🇸Oregon, Ohio, United States
Springfield Regional Cancer Center
🇺🇸Springfield, Ohio, United States
Springfield Regional Medical Center
🇺🇸Springfield, Ohio, United States
Mercy Health - Saint Anne Hospital
🇺🇸Toledo, Ohio, United States
Toledo Clinic Cancer Centers-Toledo
🇺🇸Toledo, Ohio, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
Wright-Patterson Medical Center
🇺🇸Wright-Patterson Air Force Base, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
University of Pennsylvania/Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Prisma Health Cancer Institute - Spartanburg
🇺🇸Boiling Springs, South Carolina, United States
Prisma Health Cancer Institute - Easley
🇺🇸Easley, South Carolina, United States
Greenville Health System Cancer Institute-Andrews
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Butternut
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Faris
🇺🇸Greenville, South Carolina, United States
Prisma Health Greenville Memorial Hospital
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Eastside
🇺🇸Greenville, South Carolina, United States
Prisma Health Cancer Institute - Greer
🇺🇸Greer, South Carolina, United States
Prisma Health Cancer Institute - Seneca
🇺🇸Seneca, South Carolina, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
🇺🇸Green Bay, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States