Pilot Trial of Olutasidenib Maintenance Post Allogeneic Hematopoietic Cell Transplantation in Patients Carrying IDH1 Mutation With AML, MDS, or CMML Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Incidence of adverse events (AEs)
研究概览
简要总结
This phase I trial tests the safety, side effects, and effectiveness of olutasidenib in preventing the return of disease (relapse) in patients who have undergone donor (allogeneic) hematopoietic cell transplant for acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML) carrying an IDH1 mutation. Olutasidenib is in a class of medications called IDH1 inhibitors. It works by slowing or stopping the growth of cancer cells. Giving olutasidenib may be safe, tolerable and/or effective in preventing relapse in patients with IDH1 mutated AML, MDS or CMML after an allogeneic hematopoietic cell transplant.
详细描述
PRIMARY OBJECTIVE:
I. Evaluate the safety and tolerability of olutasidenib as maintenance therapy after allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML).
SECONDARY OBJECTIVES:
I. Assess overall survival (OS) and leukemia-free survival (LFS) at 1 and 2 years after first dose of olutasidenib.
II. Estimate cumulative incidence of relapse (CIR), non-relapse mortality (NRM), graft-versus-host disease (GVHD) free, relapse-free survival (GRFS) at 1 and 2 years after first dose of olutasidenib.
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
- •Documented informed consent of the participant and/or legally authorized representative
- •Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval
- •Age: ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) ≤ 2 or Karnofsky performance status (KPS) ≥ 70
- •Patients who are scheduled to receive or have already undergone allogeneic hematopoietic cell transplantation (alloHCT) from any donor type, any conditioning regimen, and regardless of GVHD prophylaxis will be include
- •Patients must have AML, MDS, or CMML with mIDH1 diagnosis at diagnosis (regardless of time from HCT). Note: Patient with pre-HCT disease relapse will no be included if mIDH1 is not detected after relapse
- •Day 30 marrow post alloHCT should show evidence of morphologic remission with < 5% bone marrow (BM) blasts. Patients with MRD-positive status either by flow cytometry or IDH1 mutation testing will be eligible
- •Patients with previous therapy with IDH1 inhibitors will be included
- •Absolute neutrophil count (ANC) > 1000/mm^3 (within 28 days prior to day 1 of protocol)
- •Hemoglobin ≥ 8.0 gm/dL (within 28 days prior to day 1 of protocol)
- •Platelets ≥ 50,000/mm^3 (within 28 days prior to day 1 of protocol) Note: Patients with lower counts can enroll if infection cytomegalovirus (CMV)/human herpes virus 6 (HHV6), etc. is being treated actively
- •Bilirubin ≤ 2 x upper limit of normal (ULN) (within 28 days prior to day 1 of protocol) (unless has Gilbert's disease). Patients with abnormal liver function tests (LFTs) due to active GVHD will not be eligible
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2 x ULN (within 28 days prior to day 1 of protocol). Patients with abnormal LFTs due to active GVHD will not be eligible
- •Creatinine clearance of ≥ 30/min/1.73 m^2 for participants with creatinine levels above institutional normal per 24 hour urine test or the Cockcroft-Gault formula (within 28 days prior to day 1 of protocol)
- •Corrected QT interval (QTc) ≤ 480 ms (Note: To be performed within 28 days prior to day 1 of protocol therapy)
- •Seronegative for HIV antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV) (if positive, hepatitis C ribonucleic acid [RNA] quantitation must be performed), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]) (within 28 days prior to day 1 of protocol)
- •Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 28 days prior to day 1 of protocol). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •Agreement by females and males of childbearing potential, defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only), to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
排除标准
- •Patients with more than one allogeneic HCT
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to study agent
- •Active diarrhea considered clinically significant and may impair oral drug administration
- •Clinically significant uncontrolled illness
- •Uncontrolled infection requiring systemic antimicrobials
- •Active infection: Patients with treated viral, bacterial or fungal infections that are controlled on therapy will be allowed to participate
- •Participant has detectable human immunodeficiency virus (HIV) viral load within the previous 6 months (must have viral load testing prior to study enrollment if participant has a known history of HIV 1/2 antibodies)
- •Active hepatitis B or C, or HIV
- •Other active malignancy. Participants with history of prior malignancy treated with curative intent who achieved CR more than 2 years before study entry are eligible. This exclusion rule does not apply to non-melanoma skin tumors and in-situ cervical cancer
- •Females only: Pregnant or breastfeeding
- •Active grade II-IV acute GVHD per Mount Sinai Acute Graft Versus Host Disease International Consortium (MAGIC) criteria and/or requiring systemic steroids with prednisone dose equivalent of ≥ 0.25 mg/kg at end of 4 weeks. Patients with a mild form of acute GVHD involving skin, gut or liver requiring topical steroid creams or oral beclomethasone (8 mg/day), entocort, (9 mg/day) and/or solumedrol (and equivalent prednisone) will be allowed
- •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 (olutasidenib)
Starting 50-120 days after transplant, patients receive olutasidenib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study.
干预措施: Biospecimen Collection (Procedure)
Treatment (olutasidenib)
Starting 50-120 days after transplant, patients receive olutasidenib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study.
干预措施: Olutasidenib (Drug)
结局指标
主要结局
Incidence of adverse events (AEs)
时间窗: Up to 30 days after last dose of study treatment
AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Proportion of patients completing at least 6 months of study therapy
时间窗: Up to 2 years
Tolerability will be defined as the proportion of patients who complete at least 6 months of study therapy.
次要结局
- Overall survival (OS)(From start of treatment to death, assessed up to 2 years)
- Leukemia-free survival (LFS)(From start of treatment to relapse or death, assessed up to 2 years)
- Time to relapse(From start of treatment to relapse, assessed up to 2 years)
- Non-relapse mortality (NRM)(From start of treatment to death from causes other than relapse, assessed up to 2 years)
- Graft versus host disease (GVHD) free, relapse-free survival (GRFS)(From start of treatment to grade III or IV acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death, assessed up to 2 years)
- Rate of acute GVHD (aGVHD) grades II-IV and III-IV(From transplant to aGVHD onset, assessed up to 2 years)
- Incidence of chronic GVHD (cGVHD)(From start of treatment to cGVHD onset, assessed up to 2 years)