A Phase 1, Open-label, Dose-finding Study of CC-91633 (BMS-986397) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 56
- 试验地点
- 9
- 主要终点
- Dose-limiting Toxicity (DLT)
研究概览
简要总结
Study CC-91633-AML-001 is a Phase 1, open-label, dose escalation and expansion, first-in-human (FIH) clinical study of CC-91633 (BMS-986397) in participants with relapsed or refractory acute myeloid leukemia (R/R AML) or in participants with relapsed or refractory higher-risk myelodysplastic syndromes (R/R HR-MDS). The Dose Escalation part (Part A) of the study will enroll participants with R/R AML and R/R HR-MDS and will evaluate the safety and tolerability of escalating doses of CC-91633 (BMS-986397), administered orally, and determine the maximum tolerated dose (MTD) or preliminary recommended Phase 2 doses (RP2D) and schedule. Throughout the study, final decisions on dose escalation/de-escalation will be made by the safety review committee (SRC). Approximately 60 participants may be enrolled in Part A of the study.
The expansion part (Part B) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development. Approximately 60 response-evaluable subjects per indication (R/R AML or R/R HR-MDS) may be enrolled.
Parts A and B will consist of 3 periods: Screening, Treatment, and Follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Participants must satisfy the criteria below to be enrolled in the Dose Escalation (Part A) or the Dose Expansion (Part B) of this study.
- •Participant is ≥ 18 years of age, at the time of signing the ICF.
- •Participant must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- •Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
- •Relapsed or refractory acute myeloid leukemia (R/R AML) and relapsed or refractory higher-risk myelodysplastic syndromes (R/R HR-MDS) as defined by the World Health Organization (WHO) criteria who have failed or are ineligible for all available therapies which may provide clinical benefit
- •Participant has Eastern Cooperative Oncology Group Performance Status of 0 to
- •Participants must have the following screening laboratory values:
- •Total White Blood Cell count (WBC) < 25 x 109/L prior to first infusion.
- •Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN), unless considered due to leukemic organ involvement, in which case AST and ALT can be ≤ 5.0 x ULN.
- •Uric acid ≤ 7.5 mg/dL (446 μmol/L).
- •Serum total bilirubin ≤ 1.5 x ULN, unless considered due to Gilbert's syndrome
- •Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated.
- •INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN.
排除标准
- •The presence of any of the following will exclude a participant from enrollment:
- •Participant has any condition, including active or uncontrolled infection, or the presence of laboratory abnormalities, which places the participant at unacceptable risk if the participant were to participate in the study.
- •Any other significant medical condition, laboratory abnormality, or psychiatric illness which places the participant at unacceptable risk if he/she were to participate in the study or that would prevent the participant from complying with the study.
- •Participant has any condition that confounds the ability to interpret data from the study.
- •Participants with acute promyelocytic leukemia.
- •Participants with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia.
- •Participants with immediately life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolled disseminated intravascular coagulation.
- •Participants with impaired cardiac function or clinically significant cardiac diseases,
- •Participants who have undergone major surgery ≤ 2 weeks prior to starting CC-
- •Participants must have recovered from any clinically significant effects of recent surgery.
- •Pregnant or nursing individuals.
- •Participants with known human immunodeficiency virus infection.
- •Participants with known chronic, active hepatitis B virus or hepatitis C virus C (HCV) infection.
- •Participants with ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).
- •Participants with history of concurrent second cancers requiring active, ongoing systemic treatment
- •Participants with clinically significant diarrhea, vomiting or malabsorption felt to limit absorption of orally administered medications.
- •Participants with known or suspected hypersensitivity to any of the components or excipients of the study treatment or to similar class drugs (eg, lenalidomide).
研究组 & 干预措施
Participants with R/R AML and R/R HR-MDS - Part A
Part A (Dose Escalation) of the study will enroll R/R AML (Relapsed or Refractory Acute Myeloid Leukemia) and R/R HR-MDS (Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes) participants and will evaluate the safety and tolerability of escalating doses of CC-91633, administered orally, and determine the maximum tolerated dose (MTD) or preliminary recommended Phase 2 doses (RP2D) and schedule.
干预措施: CC-91633 (Drug)
Participants with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)
Part B (expansion part) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R AML participants.
干预措施: CC-91633 (Drug)
Participants with Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes (HR-MDS)
Part B (expansion part) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R HR-MDS participants.
干预措施: CC-91633 (Drug)
结局指标
主要结局
Dose-limiting Toxicity (DLT)
时间窗: Up to 42 days after first dose of study treatment in Part A
Defined as toxicities such as non-hematologic, confirmed Hy's law case, hematologic, or any AE toxicities meeting protocol specified DLT criteria and occurring within the DLT assessment period, unless the toxicity can clearly be determined to be due to other specified causes.
Incidence of Adverse Events (AEs)
时间窗: Up to 4 years
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.
Maximum Tolerated Dose (MTD)
时间窗: Up to 2 years
Defined as the dose with highest posterior probability of the Dose-limiting toxicity (DLT) rate falling in the target interval and fulfilling escalation with overdose control (EWOC).
次要结局
- Partial Remission Rate (PRR)(Up to 4 years)
- Complete Remission Rate (CRR)(Up to 4 years)
- Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Minimal residual disease negative complete remission rate (CRRMRD-)(Up to 4 years)
- Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Combined Complete Remission Rate (cCRR)(Up to 4 years)
- Stable Disease Rate (SDR)(Up to 4 years)
- Relapse-free Survival (RFS)(Up to 4 years)
- Efficacy: Time to transformation to Acute Myeloid Leukemia (AML) for High-Risk Myelodysplastic Syndrome (HR-MDS)(Up to 4 years)
- CC-91633 Pharmacokinetics - AUC(0-T)(Up to 4 years)
- CC-91633 Pharmacokinetics - AUC(TAU)(Up to 4 years)
- CC-91633 Pharmacokinetics - Tmax(Up to 4 years)
- CC-91633 Pharmacokinetics - CLT/F(Up to 4 years)
- CC-91633 Pharmacokinetics - Vz/F(Up to 4 years)
- CC-2004772 Pharmacokinetics - AUC(0-T)(Up to 4 years)
- CC-2004772 Pharmacokinetics - CLT/F(Up to 4 years)
- CC-2004772 Pharmacokinetics - Vz/F(Up to 4 years)
- Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Morphologic Leukemia-free State Rate (MLFSR)(Up to 4 years)
- Progression-free Survival (PFS) rate at 3 and 9 months(At 3 months and 9 months of PFS)
- Progression-free Survival (PFS)(Up to 4 years)
- Overall Survival (OS) rate(At 6 and 12 months of survival)
- Overall Response Rate (ORR)(Up to 4 years)
- Overall Survival (OS)(Up to 4 years)
- Event-free Survival (EFS)(Up to 4 years)
- Duration of remission/response(Up to 4 years)
- Time to remission/response(Up to 4 years)
- CC-2004772 Pharmacokinetics - AUC(TAU)(Up to 4 years)
- CC-2004772 Pharmacokinetics - Tmax(Up to 4 years)
- CC-2004772 Pharmacokinetics - T-HALF(Up to 4 years)
- CC-91633 Pharmacokinetics - Cmax(Up to 4 years)
- CC-91633 Pharmacokinetics - T-HALF(Up to 4 years)
- CC-2004772 Pharmacokinetics - Cmax(Up to 4 years)