A Multicenter Phase II Study of Blinatumomab for Treatment of Adult Patients With Morphologic Relapsed/Refractory or Measurable Residual Disease (MRD) CD19-Positive Mixed Phenotype Acute Leukemia (MPAL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Cohort A response rate
研究概览
简要总结
This is a research study to find out if a drug called blinatumomab is effective for treating patients with relapsed or refractory (R/R) or measurable residual disease (MRD) CD19-positive mixed phenotypic acute leukemia (MPAL). Measurable Residual Disease (MRD) means that there are a small number of cancer cells remaining after treatment
详细描述
This is a multicenter, non-randomized, open-label, phase II study evaluating the efficacy of blinatumomab to achieve the following objectives:
- The best morphologic response after the first two cycles of therapy in subjects with morphologic R/R CD19-positive MPAL
- MRD-negativity in subjects with CD19-positive MPAL in CR, or CRh, or CRi or CRp after receiving at least one chemotherapy block of standard ALL or AML treatment with MRD-positivity at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01%
The trial consists two groups (Group A and B) and three phases ( induction, consolidation and maintenance) of therapy. Subject will receive study drug blinatumomab by continuous IV infusion (CIV). Each treatment cycle consists of 28 days of blinatumomab CIV followed by a 14±3 days treatment-free interval for induction, 28±3 days treatment-free interval for consolidation, and 56±3 days treatment-free interval for maintenance
Blinatumomab is approved by Food and Drug Administration [FDA] and European Medicines Agency [EMA] for use in people with another type of acute leukemia called acute lymphoblastic leukemia (ALL) but not MPAL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have histologically or cytologically confirmed R/R CD19-positive MPAL based on the WHO criteria, OR CD19-positive MPAL in CR/CRh/CRi/CRp after at least one chemotherapy block of standard ALL or AML therapy with detectable MRD ≥ 0.1%. Primary refractory MPAL is defined by absence of CR/CRh/CRi/CRp after at least one cycle of standard AML/ALL induction therapy. A patient has relapsed MPAL if they achieved a CR/CRh/CRi/CRp after induction therapy (CR1) and has then relapsed during, or after continuation of therapy.
- •Age 18 years and older
- •Subjects who have undergone allo-HSCT are eligible if they are ≥ 4 weeks post stem cell infusion, have no evidence of GVHD > Grade 2, and are at least ≥ 1 week off all immunosuppressive therapy
- •Previous cytotoxic chemotherapy (except for hydroxyurea) must have been completed at least 2 weeks prior to day 1 of treatment on the study. Subjects with hematologic malignancies are expected to have hematologic abnormalities at study entry.
- •ECOG performance status < 3
- •Subjects must have organ function as below:
- •Direct bilirubin ≤ 2.5 mg/dL
- •AST/ALT/Alkaline phosphatase ≤ 5 X institutional upper limit of normal
- •Serum creatinine ≤ 3 mg/dL
- •Subjects with a history of CNS leukemia must be clinically stable with a flow cytometric clear CSF in the 2 weeks prior to day 1 of blinatumomab administration. Subjects with history of CNS leukemia in Cohort A should have received one dose of intrathecal chemotherapy in the 4 weeks prior to day 1 of blinatumomab administration. Subject can receive subsequent prophylactic intrathecal chemotherapy.
- •Female subjects of childbearing potential must have a negative pregnancy test
- •Ability to understand and willingness to sign a written informed consent document
- •Agree to comply with the study requirements and agree to come to the clinic/hospital for required study visits
排除标准
- •Subjects receiving any other investigational agents, or concurrent chemotherapy, radiation therapy, or immunotherapy not including corticosteroids or hydroxyurea
- •Subjects with acute leukemia with any of the following cytogenetic abnormalities:
- •t(15;17)(q24;q21) PML/RARA, t(8;21)(q22;q22) RUNX1/RUNX1T1, inv(16)(p13q22)/t(16;16)(p13;q22) CBFB-MYH11
- •A history or presence of clinically relevant CNS pathology (e.g., as epilepsy, paresis, aphasia, stroke, severe brain injuries, dementia, cerebellar disease, psychosis)
- •Hyperleukocytosis with > 50,000 blasts/µL. Hydroxyurea for blast count control is permitted before starting treatment and up to maximum of 10 days after starting treatment on the study. The WBC need not reach 50,000/µL to start hydroxyurea during protocol; the decision to start hydroxyurea during this time is at the discretion of the treating physician
- •Active, uncontrolled infection; subjects with infection under active treatment and controlled with antimicrobials are eligible
- •Pregnant women
- •Uncontrolled undercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements
研究组 & 干预措施
Subjects with R/R CD19-positive MPAL
Cohort A: Evaluate the efficacy of blinatumomab to achieve the best morphologic response after the first two cycles of therapy in subjects with morphologic R/R CD19-positive MPAL
- The treatment of blinatumomab consists of induction, consolidation and maintenance therapy
- Subject will receive study drug blinatumomab by continuous IV infusion (CIV)
- Each treatment cycle consists of 28 days of blinatumomab CIV followed by a 14±3 days treatment-free interval for induction, 28±3 days treatment-free interval for consolidation, and 56±3 days treatment-free interval for maintenance
- The initial dose of blinatumomab is 9 mcg/day for 7 days. The target dose for rest of treatment is 28 mcg/day
干预措施: BLINCYTO (Blinatumomab) (Drug)
Subjects with CD19-positive MPAL in CR/CRh/CRi/CRp and detectable MRD
Cohort B: Evaluate the efficacy of blinatumomab to achieve MRD-negativity in subjects with CD19-positive MPAL in CR, or CRh, or CRi or CRp after receiving at least one chemotherapy block of standard ALL or AML treatment with MRD-positivity at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01%
- The treatment of blinatumomab consists of induction, consolidation and maintenance therapy
- Subject will receive study drug blinatumomab by continuous IV infusion (CIV)
- Each treatment cycle consists of 28 days of blinatumomab CIV followed by a 14±3 days treatment-free interval for induction, 28±3 days treatment-free interval for consolidation, and 56±3 days treatment-free interval for maintenance.
- The dose of blinatumomab is 28 mcg/day
干预措施: BLINCYTO (Blinatumomab) (Drug)
结局指标
主要结局
Cohort A response rate
时间窗: through study completion, an average of 1 year
The rate of achievement of CR+CRh after the first 2 cycles of blinatumomab in Cohort A subjects
Cohort B response rate
时间窗: through study completion, an average of 1 year
The rate of achievement of MRD-negativity (\< 0.01%) after the first 2 cycles of blinatumomab in Cohort B subjects
次要结局
- Cohort A survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)
- Cohort B survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months)