Blinatumomab, Methotrexate, Cytarabine, and Ponatinib in Treating Patients With Philadelphia Chromosome-Positive, or BCR-ABL Positive, or Relapsed/Refractory, Acute Lymphoblastic Leukemia
Phase II Study of the Combination of Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)
2 other identifiers
interventional
90
1 country
1
Brief Summary
This phase II trial studies how well blinatumomab, methotrexate, cytarabine, and ponatinib work in treating patients with Philadelphia chromosome (Ph)-positive, or BCR-ABL positive, or acute lymphoblastic leukemia that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as methotrexate and cytarabine, 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. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab, methotrexate, cytarabine, and ponatinib may work better in treating patients with acute lymphoblastic leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Nov 2017
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 24, 2017
CompletedFirst Posted
Study publicly available on registry
August 28, 2017
CompletedStudy Start
First participant enrolled
November 29, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 30, 2027
February 25, 2026
February 1, 2026
10 years
August 24, 2017
February 23, 2026
Conditions
Outcome Measures
Primary Outcomes (5)
Complete molecular response (CMR) rate in newly diagnosed Ph-positive and/or BCR-ABL-positive acute lymphoblastic leukemia (ALL)
At 18 weeks
Overall response rate (ORR) in relapsed/refractory ALL
This is defined as the percentage of patients achieving complete remission (CR) or CR with incomplete blood count recovery (CRi).
At 12 weeks
Relapse-free survival
From documented complete response until relapse or death, assessed up to 6 years
Event-free survival
From first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 6 years
Overall survival
First day of treatment to time of death from any cause, assessed up to 6 years
Study Arms (1)
Treatment (blinatumomab, chemotherapy, ponatinib)
EXPERIMENTALPatients receive blinatumomab IV nonstop on days 1-28 of cycles 1-5, and methotrexate and cytarabine intrathecally (by spinal tap) on days 1, 15, and 29 of cycles 1-4. Patients also receive ponatinib PO daily. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given intrathecally via spinal tap
Given intrathecally via spinal tap
Given PO
Eligibility Criteria
You may qualify if:
- Diagnosis of one of the following:
- Participants ≥ 18 years of age with previously untreated Ph-positive ALL \[either t(9;22) and/or BCR-ABL positive\] (includes patients initiated on first course of therapy before cytogenetics known) or with lymphoid accelerated or blast phase CML. These participants could have received one or two courses of chemotherapy with or without other TKIs and still eligible. (Participants with lymphoid accelerated or blast phase CML will be evaluated separately) i. If they achieved CR, they are assessable only for event-free and overall survival, or ii. If they failed to achieve CR, they are assessable for CR, event-free, and overall survival
- Participants ≥ 18 years of age with relapsed/refractory Ph-positive ALL or with previously treated lymphoid accelerated or blast phase CML (Participants with lymphoid accelerated or blast phase CML will be evaluated separately)
- Participants ≥ 18 years of age with ALL MRD positive (either by NGS or PCR or flowcytometry) or with previously treated lymphoid accelerated or blast phase CML (Participants with lymphoid accelerated or blast phase CML will be evaluated separately)
- Performance status ≤ 2 (ECOG Scale)
- Adequate liver function as defined by the following criteria (unless the increased values are judged to be leukemia disease related):
- Total serum bilirubin ≤ 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome
- Alanine aminotransferase (ALT) ≤ 3 x ULN, OR
- Aspartate aminotransferase (AST) ≤ 3 x ULN
- Adequate pancreatic function as defined by the following criteria:
- a) Serum lipase and amylase ≤ 1.5 x ULN
- For females of childbearing potential, a negative urine pregnancy test must be documented
- Female participants who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- +6 more criteria
You may not qualify if:
- Active serious infection not controlled by oral or intravenous antibiotics.
- History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
- History of alcohol abuse
- Uncontrolled hypertriglyceridemia (triglycerides \> 650mg/L)
- Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) that in the investigator's opinion will shorten survival to less than 1 year.
- Active Grade III-V cardiac failure as defined by the New York Heart Association Criteria.
- Uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- Myocardial infarction (MI), stroke, or revascularization within 3 months
- Unstable angina or transient ischemic attack
- Congestive heart failure prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment
- Diagnosed or suspected congenital long QT syndrome
- Clinically significant atrial or ventricular arrhythmias (such as artrial fibrillation, ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) as determined by the treating physician
- Prolonged QTc interval on pre-entry electrocardiogram (\> 470 msec) unless corrected after electrolyte replacement or approved by cardiologist
- Significant venous or arterial thromboembolism including deep venous thrombosis or pulmonary embolism. Participants with a history of treated prior superficial or catheter associated will not be considered as significant embolism and after discussion with PI will not be excluded from eligibility.
- Uncontrolled hypertension (diastolic blood pressure \>90mmHg; systolic \>140mmHg). Participants with hypertension should be under treatment on study entry to effect blood pressure control
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
- Amgencollaborator
- Takedacollaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (3)
Short NJ, Kantarjian H, Furudate K, Jain N, Ravandi F, Karrar O, Loghavi S, Nasr L, Haddad FG, Senapati J, Garris R, Takahashi K, Jabbour E. Molecular characterization and predictors of relapse in patients with Ph + ALL after frontline ponatinib and blinatumomab. J Hematol Oncol. 2025 May 14;18(1):55. doi: 10.1186/s13045-025-01709-y.
PMID: 40369607DERIVEDKantarjian H, Short NJ, Haddad FG, Jain N, Huang X, Montalban-Bravo G, Kanagal-Shamanna R, Kadia TM, Daver N, Chien K, Alvarado Y, Garcia-Manero G, Issa GC, Garris R, Nasnas C, Nasr L, Ravandi F, Jabbour E. Results of the Simultaneous Combination of Ponatinib and Blinatumomab in Philadelphia Chromosome-Positive ALL. J Clin Oncol. 2024 Dec 20;42(36):4246-4251. doi: 10.1200/JCO.24.00272. Epub 2024 Jul 19.
PMID: 39028925DERIVEDJabbour E, Short NJ, Jain N, Huang X, Montalban-Bravo G, Banerjee P, Rezvani K, Jiang X, Kim KH, Kanagal-Shamanna R, Khoury JD, Patel K, Kadia TM, Daver N, Chien K, Alvarado Y, Garcia-Manero G, Issa GC, Haddad FG, Kwari M, Thankachan J, Delumpa R, Macaron W, Garris R, Konopleva M, Ravandi F, Kantarjian H. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023 Jan;10(1):e24-e34. doi: 10.1016/S2352-3026(22)00319-2. Epub 2022 Nov 16.
PMID: 36402146DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elias Jabbour
M.D. Anderson Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 24, 2017
First Posted
August 28, 2017
Study Start
November 29, 2017
Primary Completion (Estimated)
November 30, 2027
Study Completion (Estimated)
November 30, 2027
Last Updated
February 25, 2026
Record last verified: 2026-02