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

NCT ID: NCT02143414

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2026-06-24

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort I (blinatumomab, POMP)

See Detailed Description

Group Type: EXPERIMENTAL

Biopsy Procedure

Intervention Type: PROCEDURE

Undergo a biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo a blood sample collection

Blinatumomab

Intervention Type: BIOLOGICAL

Given IV

Bone Marrow Aspiration and Biopsy

Intervention Type: PROCEDURE

Undergo a bone marrow aspiration and biopsy

Computed Tomography

Intervention Type: PROCEDURE

Undergo a CT scan

Echocardiography Test

Intervention Type: PROCEDURE

Undergo ECHO

Lumbar Puncture

Intervention Type: PROCEDURE

Undergo a lumbar puncture

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given PO

Methotrexate Sodium

Intervention Type: DRUG

Given PO

Prednisone

Intervention Type: DRUG

Given PO

Vincristine

Intervention Type: DRUG

Given IV

Vincristine Sulfate

Intervention Type: DRUG

Given IV

X-Ray Imaging

Intervention Type: PROCEDURE

Undergo an x-ray

Cohort II (dasatinib, prednisone, blinatumomab)

See Detailed Description

Group Type: EXPERIMENTAL

Biopsy Procedure

Intervention Type: PROCEDURE

Undergo a biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo a blood sample collection

Blinatumomab

Intervention Type: BIOLOGICAL

Given IV

Bone Marrow Aspiration and Biopsy

Intervention Type: PROCEDURE

Undergo a bone marrow aspiration and biopsy

Computed Tomography

Intervention Type: PROCEDURE

Undergo a CT scan

Dasatinib

Intervention Type: DRUG

Given PO

Echocardiography Test

Intervention Type: PROCEDURE

Undergo ECHO

Lumbar Puncture

Intervention Type: PROCEDURE

Undergo a lumbar puncture

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Prednisone

Intervention Type: DRUG

Given PO

X-Ray Imaging

Intervention Type: PROCEDURE

Undergo an x-ray

Interventions

Biopsy Procedure

Undergo a biopsy

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo a blood sample collection

Intervention Type: PROCEDURE

Blinatumomab

Given IV

Intervention Type: BIOLOGICAL

Bone Marrow Aspiration and Biopsy

Undergo a bone marrow aspiration and biopsy

Intervention Type: PROCEDURE

Computed Tomography

Undergo a CT scan

Intervention Type: PROCEDURE

Dasatinib

Given PO

Intervention Type: DRUG

Echocardiography Test

Undergo ECHO

Intervention Type: PROCEDURE

Lumbar Puncture

Undergo a lumbar puncture

Intervention Type: PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

Mercaptopurine

Given PO

Intervention Type: DRUG

Methotrexate

Given PO

Intervention Type: DRUG

Methotrexate Sodium

Given PO

Intervention Type: DRUG

Prednisone

Given PO

Intervention Type: DRUG

Vincristine

Given IV

Intervention Type: DRUG

Vincristine Sulfate

Given IV

Intervention Type: DRUG

X-Ray Imaging

Undergo an x-ray

Intervention Type: PROCEDURE

Other Intervention Names

Biopsy; BIOPSY_TYPE; Bx; Biological Sample Collection; Biospecimen Collected; Specimen Collection; AMG 103; AMG-103; AMG103; Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody; Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103; Blincyto; MEDI 538; MEDI-538; MEDI538; MT 103; MT-103; MT103; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; tomography; BMS 354825; BMS-354825; BMS354825; Dasatinib Hydrate; Dasatinib Monohydrate; Sprycel; EC; Echocardiography; LP; Spinal Tap; Magnetic Resonance; Magnetic Resonance Imaging (MRI); Magnetic resonance imaging (procedure); Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI; MRI Scan; MRIs; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Structural MRI; 3H-Purine-6-thiol; 6 MP; 6 Thiohypoxanthine; 6 Thiopurine; 6-Mercaptopurine; 6-Mercaptopurine Monohydrate; 6-MP; 6-Purinethiol; 6-Thiopurine; 6-Thioxopurine; 6H-Purine-6-thione, 1,7-dihydro- (9CI); 7-Mercapto-1,3,4,6-tetrazaindene; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; Purinethol; U-4748; WR-2785; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Jylamvo; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate; Mexate-AQ; MTX; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; Sodium Methotrexate; Trexall; Xatmep; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltasone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Orasone; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; LCR; Leurocristine; VCR; Vincrystine; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; Conventional X-Ray; Diagnostic Radiology; Medical Imaging, X-Ray; Plain film radiographs; Radiographic Imaging; Radiographic imaging procedure (procedure); Radiography; RG; Static X-Ray; X-Ray

Eligibility Criteria

Inclusion Criteria

• 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
• 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)
• 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
• 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
• Cohort I, Ph-negative Patients Only: Patients must not have any known autoimmune disease
• 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
• 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
• 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
• 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
• 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
• 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
• 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)
• All non-hematologic treatment related toxicities that are deemed clinically significant by the treating investigator must have resolved to =< grade 2
• 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
• Registration Step 3 - Maintenance: Patients must have adequate marrow function as evidenced by platelets >= 75,000/mcL within 28 days prior to registration
• 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

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anjali S Advani

Role: PRINCIPAL_INVESTIGATOR

SWOG Cancer Research Network

Locations

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

Beacon Kalamazoo

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

Sainte Genevieve County Memorial Hospital

Sainte Genevieve, Missouri, United States

Mercy Hospital Springfield

Springfield, Missouri, United States

CoxHealth South Hospital

Springfield, Missouri, United States

Mercy Infusion Center - Chippewa

St Louis, Missouri, United States

Missouri Baptist Medical Center

St Louis, Missouri, United States

Mercy Hospital Saint Louis

St Louis, 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

Countries

United States

References

Advani AS, Moseley A, O'Dwyer KM, Wood BL, Park J, Wieduwilt M, Jeyakumar D, Yaghmour G, Atallah EL, Gerds AT, O'Brien SM, Liesveld JL, Othus M, Litzow M, Stone RM, Sharon E, Erba HP. Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia. Blood Adv. 2023 Apr 11;7(7):1279-1285. doi: 10.1182/bloodadvances.2022008216.

Reference Type: DERIVED

PMID: 36322825 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2014-01047

Identifier Type: REGISTRY

Identifier Source: secondary_id

SWOG-S1318

Identifier Type: -

Identifier Source: secondary_id

S1318

Identifier Type: OTHER

Identifier Source: secondary_id

S1318

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180888

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2014-01047

Identifier Type: -

Identifier Source: org_study_id