A Phase 1, Open-label, Dose Finding Study of CC-90009, a Novel Cereblon E3 Ligase Modulating Drug, in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes
Overview
- Phase
- Phase 1
- Intervention
- CC-90009
- Conditions
- Leukemia, Myeloid, Acute
- Sponsor
- Celgene
- Enrollment
- 101
- Locations
- 20
- Primary Endpoint
- Number of Participants With Dose Limiting Toxicity (DLTs)
- Status
- Terminated
- Last Updated
- 10 months ago
Overview
Brief Summary
CC-90009-AML-001 is a phase 1, open-label, dose escalation and expansion, study in subjects with relapsed or refractory acute myeloid leukemia and relapsed or refractory higher-risk myelodysplastic syndrome.
Detailed Description
Study CC-90009-AML-001 is an open-label, Phase 1, dose escalation and expansion, first-in-human clinical study of CC-90009 in subjects with relapsed or refractory acute myeloid leukemia (AML) and relapsed or refractory higher-risk myelodysplastic syndrome. The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of CC-90009 in relapsed and refractory AML. The expansion part, (Part B), will further evaluate the safety and efficacy of CC-90009 administered at or below the maximum tolerated dose (MTD) in selected expansion cohorts of one or more dosing regimens in order to determine the recommended Phase 2 dose (RP2D) for subjects with relapsed or refractory AML and relapsed or refractory higher-risk myelodysplastic syndrome.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women ≥ 18 years of age, at the time of signing the ICD (Informed Consent Document).
- •Subject must understand and voluntarily sign an ICD prior to any study-related assessments/procedures being conducted.
- •Relapsed or refractory AML (Acute Myeloid Leukemia) (Parts A and B) or relapsed or refractory (R/R) higher-risk MDS (Myelodysplastic Syndrome) (HR-MDS) (Part B only) as defined by World Health Organization criteria who are not suitable for other established therapies.
- •In Part A, R/R AML
- •In Part B, R/R AML including
- •Relapsed after allogeneic HSCT or
- •In second or later relapse or
- •Refractory to initial induction or re-induction treatment or
- •Refractory or relapse after HMA treatment (HMA failure defined as primary progression or lack of clinical benefit after a minimum of 6 cycles or unable to tolerate HMA due to toxicity) or
- •Refractory within 1 year of initial treatment (excluding those with favorable risk based on cytogenetics)
Exclusion Criteria
- •Subjects with acute promyelocytic leukemia (APL)
- •Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is clinical suspicion of CNS involvement by leukemia during screening.
- •Patients with prior autologous hematopoietic stem cell transplant who, in the investigator's judgment, have not fully recovered from the effects of the last transplant (e.g., transplant related side effects).
- •Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-
- •Subjects on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD).
- •Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks prior to starting CC-90009, whichever is shorter. Hydroxyurea is allowed to control peripheral leukemia blasts.
- •Leukapheresis ≤ 2 weeks prior to starting CC-90009.
Arms & Interventions
CC-90009 - Part A
Will be administered intravenously per dosing schedule in a 28-day cycle.
Intervention: CC-90009
CC-90009 - Part B - AML and MDS patients
Relapsed or refractory AML and MDS subjects. IP will be administered intravenously per dosing schedule determined in Part A
Intervention: CC-90009
Outcomes
Primary Outcomes
Number of Participants With Dose Limiting Toxicity (DLTs)
Time Frame: From first dose to at least 28 days and up to 42 days post first dose (Up to 42 days)
A participant evaluable for DLT is defined as one that: Has received at least 80% of the total planned Cycle 1 dose (eg, ≥ 4 CC-90009 doses for the Days 1-5 schedule to be completed on or before Day 10, ≥ 6 CC-90009 doses for the Days 1- 7 schedule to be completed on or before Day 10, ≥8 doses by Day 14 for the Days 1-10 schedule, or ≥ 5 doses by Day 14 for the D1-3/D8-10 schedule) of CC-90009 during Cycle 1 without experiencing a DLT, Or; Experienced a DLT after receiving at least one dose (or fraction thereof) of CC-90009 in part A.
Secondary Outcomes
- Change From Baseline for Electrocardiogram (ECG) by Test - Parameters 2(From baseline until 28 days post last dose (Up to 25 months))
- Objective Response Rate (ORR)(Up to approximately 25 months after the last dose)
- Time to Remission/Response (TTR)(Up to approximately 25 months after the last dose)
- Renal Clearance (CLr)(Cycle 1 Day 1(C1D1). 1 cycle = 28 days)
- Non-Tolerated Dose (NTD) of CC-90009(From first dose to at least 28 days and up to 42 days post first dose (Up to 42 days))
- Change From Baseline by Laboratory Test - Chemistry Parameters 1(From baseline until 28 days post last dose (Up to 25 months))
- Maximum Tolerated Dose (MTD) of CC-90009(From first dose to at least 28 days and up to 42 days post first dose (Up to 42 days))
- Change From Baseline by Laboratory Test - Chemistry Parameters 3(From baseline until 28 days post last dose (Up to 25 months))
- Change From Baseline for Vital Signs by Test - Parameters 1(From baseline until 28 days post last dose (Up to 25 months))
- Change From Baseline for Vital Signs by Test - Parameters 2(From baseline until 28 days post last dose (Up to 25 months))
- Change From Baseline for Vital Signs by Test - Parameters 3(From baseline until 28 days post last dose (Up to 25 months))
- Change From Baseline for Electrocardiogram (ECG) by Test - Parameters 1(From baseline until 28 days post last dose (Up to 25 months))
- Eastern Cooperative Oncology Group (ECOG) Performance Status(From baseline until 28 days post last dose (Up to 25 months))
- Left Ventricular Ejection Fraction (LVEF) Percent Change From Baseline(From baseline until 28 days post last dose (Up to 25 months))
- Overall Survival (OS)(Up to approximately 25 months after the last dose)
- Relapse-free Survival (RFS)(Up to approximately 25 months after the last dose)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From first dose until 28 days post last dose (Up to 25 months))
- Event-free Survival (EFS)(Up to approximately 25 months after the last dose)
- Duration of Remission/Response (DOR)(Up to approximately 25 months after the last dose)
- Time to Acute Myeloid Leukemia (AML) Transformation(Up to approximately 88 months)
- Change From Baseline by Laboratory Test - Chemistry Parameters 2(From baseline until 28 days post last dose (Up to 25 months))
- Change From Baseline for Vital Signs by Test - Parameters 4(From baseline until 28 days post last dose (Up to 25 months))
- Progression-free Survival (PFS)(Up to approximately 25 months after the last dose)
- Maximum Observed Plasma Concentration (Cmax)(Cycle 1 Day 1(C1D1), C1D5, C1D7, C1D8, C1D10,)
- Complete Remission Rate (CRR)(Up to approximately 88 months)
- Total Body Clearance (CL)(Cycle 1 Day 1(C1D1), C1D5, C1D7, C1D8, C1D10. 1 cycle = 28 days)
- Time to Peak Plasma Concentration (Tmax)(Cycle 1 Day 1(C1D1), C1D5, C1D7, C1D8, C1D10. 1 cycle = 28 days)
- Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Post-dose (AUC 0 - 24)(Cycle 1 Day 1(C1D1), C1D5, C1D7, C1D8, C1D10. 1 cycle = 28 days)
- Terminal Phase Elimination Half-life (T1/2)(Cycle 1 Day 1(C1D1) and C1D5. 1 cycle = 28 days)
- Volume of Distribution (Vz)(Cycle 1 Day 1(C1D1) and C1D5. 1 cycle = 28 days)