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)
概览
- 阶段
- 2 期
- 干预措施
- Blinatumomab
- 疾病 / 适应症
- Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Event-free survival
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES: I. To evaluate the complete molecular response rate in cohort 1 (newly diagnosed Philadelphia chromosome \[Ph-positive\] and/or BCR-ABL-positive acute lymphoblastic leukemia \[ALL\]) and the overall response (complete remission \[CR\]+CR with incomplete blood count recovery \[CRi\]) rate in cohort 2 (relapsed/refractory disease). SECONDARY OBJECTIVES: I. To evaluate other clinical efficacy endpoints (complete cytogenetic response, complete molecular response \[CMR\], event-free survival \[EFS\] and overall survival \[OS\]) and safety of the regimen. EXPLORATORY OBJECTIVES: I. To characterize the role of ABL1 kinase domain mutations on treatment failure and relapse in patients with Ph+ ALL treated with blinatumomab ponatinib. II. To determine the impact of recurrent genomic alterations at diagnosis on relapse-free survival (RFS) in patients with Ph+ ALL treated with blinatumomab plus ponatinib. III. To investigate the impact of next-generation sequencing-based minimal residual disease assessment on relapse-free survival in patients with Ph+ ALL. IV. To determine the effect on immune cell subsets in patients with Ph+ ALL treated with blinatumomab plus ponatinib. OUTLINE: Patients receive blinatumomab intravenously (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 orally (PO) daily. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and every 6 months thereafter.
研究者
入排标准
入选标准
- •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:
排除标准
- •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
研究组 & 干预措施
Treatment (blinatumomab, chemotherapy, ponatinib)
Patients 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.
干预措施: Blinatumomab
Treatment (blinatumomab, chemotherapy, ponatinib)
Patients 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.
干预措施: Cytarabine
Treatment (blinatumomab, chemotherapy, ponatinib)
Patients 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.
干预措施: Methotrexate
Treatment (blinatumomab, chemotherapy, ponatinib)
Patients 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.
干预措施: Ponatinib
结局指标
主要结局
Event-free survival
时间窗: From first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 6 years
Overall survival
时间窗: First day of treatment to time of death from any cause, assessed up to 6 years
Overall response rate (ORR) in relapsed/refractory ALL
时间窗: At 12 weeks
This is defined as the percentage of patients achieving complete remission (CR) or CR with incomplete blood count recovery (CRi).
Complete molecular response (CMR) rate in newly diagnosed Ph-positive and/or BCR-ABL-positive acute lymphoblastic leukemia (ALL)
时间窗: At 18 weeks
Relapse-free survival
时间窗: From documented complete response until relapse or death, assessed up to 6 years