Pilot Study of Asciminib as a Maintenance Treatment Post Cellular Therapies in Adults With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase I trial tests the safety, side effects and best dose of asciminib as maintenance treatment for adults with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) who have undergone cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor (CAR) T cell therapy. Maintenance treatment is given to help keep cancer from coming back after it has disappeared following initial therapy. Asciminib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving asciminib may be safe and tolerable as maintenance treatment for adult patients with Philadelphia chromosome positive ALL who have undergone cellular therapies.
详细描述
PRIMARY OBJECTIVES:
I. Evaluate the safety of asciminib maintenance in adults with Philadelphia chromosome (Ph)+ acute lymphoblastic leukemia (ALL) in morphological complete remission (CR) post hematopoietic stem cell transplantation (HSCT; Arm 1) or chimeric antigen receptor (CAR) T cell therapy (Arm 2).
II. Determine the recommended phase 2 dosing (RP2D) of asciminib maintenance post cellular therapies in Ph+ ALL in each arm.
SECONDARY OBJECTIVES:
I. Evaluate feasibility of asciminib maintenance measured as the number of patients who continue asciminib > 3 cycles post cellular therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •PRE-SCREENING: Documented informed consent of the participant and/or legally authorized representative
- •PRE-SCREENING: Age ≥ 18 years
- •PRE-SCREENING: Participant was diagnosed with Ph+ ALL according to World Health Organization criteria. The BCR::ABL1 translocation may be detected by fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), next generation sequencing (NGS), or cytogenetics at least once any time prior to cellular therapy. Participants may have p190 or p220 isoform, and participants with T315I mutation are not excluded
- •PRE-SCREENING: Participant meets one of the following criteria:
- •Arm 1: Have a date for HSCT scheduled within the next 30 days or have received HSCT within the last 30 days. Note: all HSCT donors, conditioning regimens, and GVHD prophylaxis regimens will be acceptable.
- •Arm 2: Have a date for CAR T cell infusion scheduled within the next 30 days or have received CAR T cell infusion within the last 30 days
- •PRE-SCREENING: History of pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
- •PRE-SCREENING: History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Documented informed consent of the participant and/or legally authorized representative.
- •Assent, when appropriate, will be obtained per institutional guidelines
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Eastern Cooperative Oncology Group (ECOG) ≤ 2
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Participant is between day +30 and +150 after one of the following cellular therapies:
- •Arm 1: HSCT
- •Participants on Arm 1 must be fully engrafted post-HSCT.
- •Arm 2: CD19-targeted CAR T cell therapy (brexucabtagene autoleucel, tisagenlecleucel, obecabtagene autoleucel, investigational CD19 CAR T cell therapy)
- •Participants on Arm 2 must be fully recovered from cytopenia
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Day 30 (+/- 5 days) marrow post cellular therapy should show evidence of complete morphologic remission defined as < 5% bone marrow (BM) blasts, no extramedullary disease, and transfusion independence
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Participant should have no morphological evidence of relapse
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Absolute neutrophil count (ANC) ≥ 500/mm^3 for 3 days
- •NOTE: Patients are allowed growth factors
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Platelets ≥ 75,000/mm^3
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Hemoglobin ≥ 9g/dL
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Aspartate aminotransferase (AST) ≤ 3.0 x ULN
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Alanine aminotransferase (ALT) ≤ 3.0 x ULN
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: serum creatinine <1.5 mg/dL
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Left ventricular ejection fraction (LVEF) ≥ 50%
- •Note: To be performed within 28 days prior to day 1 of protocol therapy
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Bazett's corrected QT interval (QTcB) ≤ 480 ms
- •Note: To be performed within 28 days prior to day 1 of protocol therapy
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Oxygen (O2) saturation > 90% on room air
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Seronegative for HIV antigen (Ag)/antibody (Ab) combination (combo), hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) OR
- •If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Meets other institutional and federal requirements for infectious disease titer requirements
- •Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 120 days after the last dose of protocol therapy.
- •Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
排除标准
- •Prior treatment failure with asciminib
- •Treatment with strong inducers of CYP3A is not allowed and should be switched to an alternative at least 1 week prior to the start of study treatment
- •ARM 1: Treatment with prior HSCT is allowed
- •ARM 2: Treatment with prior CAR T cell therapy is allowed
- •Cardiac or cardiac repolarization abnormality, including any of the following:
- •History within 6 months prior to starting study treatment of myocardial infarction (MI), or coronary artery bypass graft (CABG)
- •Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
- •Fridericia's corrected QT interval (QTcF) at screening ≥ 450 msec (male patients), ≥ 470 msec (female patients)
- •Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome
- •History of pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
- •ARM 1: Active grade 3 or higher graft-versus-host disease (GVHD) after allogeneic HSCT within 14 days of enrollment. Note: prednisone administration (flat dose of 0.5 mg/kg) is allowed. Patients receiving any other medication to control active/progressive GVHD will be excluded
- •Clinically significant uncontrolled illness
- •Active infection not responding to treatment
- •Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •Females only: Pregnant or breastfeeding
- •Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
研究组 & 干预措施
Treatment (Asciminib)
Patients receive asciminib PO QD or BID on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening and as clinically indicated, and bone marrow biopsy, bone marrow aspirate and blood sample collection throughout the study.
干预措施: Asciminib (Drug)
Treatment (Asciminib)
Patients receive asciminib PO QD or BID on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening and as clinically indicated, and bone marrow biopsy, bone marrow aspirate and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Treatment (Asciminib)
Patients receive asciminib PO QD or BID on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening and as clinically indicated, and bone marrow biopsy, bone marrow aspirate and blood sample collection throughout the study.
干预措施: Bone Marrow Biopsy (Procedure)
Treatment (Asciminib)
Patients receive asciminib PO QD or BID on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening and as clinically indicated, and bone marrow biopsy, bone marrow aspirate and blood sample collection throughout the study.
干预措施: Echocardiography Test (Procedure)
Treatment (Asciminib)
Patients receive asciminib PO QD or BID on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening and as clinically indicated, and bone marrow biopsy, bone marrow aspirate and blood sample collection throughout the study.
干预措施: Survey Administration (Other)
Treatment (Asciminib)
Patients receive asciminib PO QD or BID on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening and as clinically indicated, and bone marrow biopsy, bone marrow aspirate and blood sample collection throughout the study.
干预措施: Bone Marrow Aspiration (Procedure)
结局指标
主要结局
Incidence of adverse events
时间窗: From start of treatment on day 1 to the end of cycle 1 on day 28
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The toxicity/adverse event information recorded on each subject will include type, severity, duration, attribution/ association with the study agent by arm and cycle. Tables will be constructed to summarize the observed incidence, severity and type of toxicity, including infection. Point estimates and 90% confidence intervals will be provided.
次要结局
- Number of patients who have completed at least 3 cycles of asciminib and have taken ≥ 70% planned doses in each cycle post cellular therapy(Up to completion of 3 cycles (cycle length= 28 days))
- Duration of remission(Up to 1 year after completion of study treatment)
- Relapse including minimal residual disease (MRD) relapsed(Up to 1 year after completion of study treatment)
- Relapse free survival(From start of protocol therapy to relapse, or death, up to 1 year after completion of study treatment)
- Overall survival(From start of protocol therapy to death regardless of cause, up to 1 year after completion of study treatment)
- Non-relapse mortality(From start of protocol therapy to death without relapse/progression, up to 1 year after completion of study treatment)
- Switching tyrosine kinase inhibitors (TKI)(Up to 1 year after completion of study treatment)
- Asciminib discontinuation(Up to 1 year)
- Asciminib interruption(Up to 1 year)
- Rate of acute graft versus host disease (aGVHD) of grades 2-4 (arm 1)(From hematopoietic stem cell transplantation (HSCT) to day 180 post HSCT)
- Rate of aGVHD of grades 3-4 (Arm 1)(From HSCT to day 180 post HSCT)
- GVHD-free, relapse-free survival (Arm 1)(From start of protocol therapy to the first observation of developing grade 3-4 aGVHD, chronic (c) GVHD requiring systemic therapy, relapse/progression, or death, whichever comes first, up to 1 year after completion of study treatment)