Clinical trial NCT04951778: Study to Evaluate Safety and Tolerability of CC-91633 (BMS-986397) in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Keywords: Relapsed or Refractory Acute Myeloid Leukemia
Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2021-07-07
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

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 2.
* 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.

Exclusion Criteria:

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-91633. 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).

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Up to 2 years
measure: Dose-limiting Toxicity (DLT)
timeFrame: Up to 42 days after first dose of study treatment in Part A
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Complete Remission Rate (CRR)
timeFrame: Up to 4 years
measure: Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Minimal residual disease negative complete remission rate (CRRMRD-)
timeFrame: Up to 4 years
measure: Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Combined Complete Remission Rate (cCRR)
timeFrame: Up to 4 years
measure: Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Morphologic Leukemia-free State Rate (MLFSR)
timeFrame: Up to 4 years
measure: Partial Remission Rate (PRR)
timeFrame: Up to 4 years
measure: Stable Disease Rate (SDR)
timeFrame: Up to 4 years
measure: Progression-free Survival (PFS) rate at 3 and 9 months
timeFrame: At 3 months and 9 months of PFS
measure: Overall Survival (OS) rate
timeFrame: At 6 and 12 months of survival
measure: Overall Response Rate (ORR)
timeFrame: Up to 4 years
measure: Overall Survival (OS)
timeFrame: Up to 4 years
measure: Relapse-free Survival (RFS)
timeFrame: Up to 4 years
measure: Progression-free Survival (PFS)
timeFrame: Up to 4 years
measure: Event-free Survival (EFS)
timeFrame: Up to 4 years
measure: Duration of remission/response
timeFrame: Up to 4 years
measure: Time to remission/response
timeFrame: Up to 4 years
measure: Efficacy: Time to transformation to Acute Myeloid Leukemia (AML) for High-Risk Myelodysplastic Syndrome (HR-MDS)
timeFrame: Up to 4 years
measure: CC-91633 Pharmacokinetics - Cmax
timeFrame: Up to 4 years
measure: CC-91633 Pharmacokinetics - AUC(0-T)
timeFrame: Up to 4 years
measure: CC-91633 Pharmacokinetics - AUC(TAU)
timeFrame: Up to 4 years
measure: CC-91633 Pharmacokinetics - Tmax
timeFrame: Up to 4 years
measure: CC-91633 Pharmacokinetics - T-HALF
timeFrame: Up to 4 years
measure: CC-91633 Pharmacokinetics - CLT/F
timeFrame: Up to 4 years
measure: CC-91633 Pharmacokinetics - Vz/F
timeFrame: Up to 4 years
measure: CC-2004772 Pharmacokinetics - Cmax
timeFrame: Up to 4 years
measure: CC-2004772 Pharmacokinetics - AUC(0-T)
timeFrame: Up to 4 years
measure: CC-2004772 Pharmacokinetics - AUC(TAU)
timeFrame: Up to 4 years
measure: CC-2004772 Pharmacokinetics - Tmax
timeFrame: Up to 4 years
measure: CC-2004772 Pharmacokinetics - T-HALF
timeFrame: Up to 4 years
measure: CC-2004772 Pharmacokinetics - CLT/F
timeFrame: Up to 4 years
measure: CC-2004772 Pharmacokinetics - Vz/F
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Local Institution - 107
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 101
state: Massachusetts
city: Saint Louis
country: United States
facility: Local Institution - 105
state: Missouri
city: Houston
country: United States
facility: Local Institution - 104
state: Texas
city: Seattle
country: United States
facility: Local Institution - 109
state: Washington
city: Barcelona
country: Spain
facility: Local Institution - 302
city: Barcelona
country: Spain
facility: Local Institution - 301
city: Madrid
country: Spain
facility: Local Institution - 303
city: Sevilla
country: Spain
facility: Local Institution - 304
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: