A Dose-finding Study of CC-90009 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-risk Myelodysplastic Syndromes

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

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.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: CC-90009

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.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 201
• France
  • Lillie Cedex, France, 59037
    • Local Institution - 505
  • Marseille Cedex 9, France, 13273
    • Institut Paoli Calmettes
  • Pierre Benite, France, 69310
    • Hôpital Lyon Sud
  • Toulouse, France, 31059
    • Local Institution - 502
• Norway
  • Bergen, Norway, N-5053
    • Local Institution - 700
  • Oslo, Norway, N-0027
    • Local Institution - 701
• Spain
  • Badalona, Spain, 8916
    • Local Institution - 603
  • Barcelona, Spain, 08036
    • Local Institution - 602
  • Madrid, Spain, 28033
    • Local Institution - 604
  • Pamplona, Spain, 31008
    • Local Institution - 605
  • Salamanca, Spain, 37007
    • Local Institution - 601
  • Valencia, Spain, 46009
    • Local Institution - 600
• United Kingdom
  • Oxford, United Kingdom, 0X3 7LE
    • Local Institution - 301
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Local Institution - 105
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution - 102
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Local Institution - 103
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Local Institution - 101
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 104

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women ≥ 18 years of age, at the time of signing the ICD (Informed Consent Document).
2. Subject must understand and voluntarily sign an ICD prior to any study-related assessments/procedures being conducted.

3. 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.

   1. In Part A, R/R AML

   2. 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)

   3. In Part B, R/R HR-MDS (Revised International Prognostic Scoring System score (IPSS-R) > 3.5 points, IPSS-R calculated during screening period):

      • IPSS-R intermediate risk (in combination with more than 10% bone marrow blasts or poor or very poor IPSS-R cytogenetic risk) or
      • IPSS-R high or
      • IPSS-R very high risk
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.
5. At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion (DLI) without conditioning.

6. Subjects must have the following screening laboratory values:

   • Corrected serum Ca or free (ionized) serum Ca within normal limits (WNL).

     o Corrected Ca (mg/dL) = Total Ca (mg/dL) - 0.8 (albumin [g/dL] - 4)

   • Total White Blood Cell count (WBC) < 25 x 10^9/L prior to first infusion. Prior or concurrent treatment with hydroxyurea to achieve this level is allowed.
   • Potassium and magnesium within normal limits or correctable with supplements.
   • Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine aminotransferase/serum glutamate pyruvic transaminase (ALT/SGPT) ≤ 2.5 x Upper Limit of Normal (ULN).
   • Uric acid ≤ 7.5 mg/dL (446 μmol/L). Prior and/or concurrent treatment with hypouricemic agents (eg, allopurinol, rasburicase) are allowed.
   • Selected electrolytes within normal limits or correctable with supplements.
   • Serum bilirubin ≤ 1.5 x ULN (upper limit of normal).
   • 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.
   • International normalized ratio (INR) < 1.5 x ULN and Partial thromboplastin time (PTT) < 1.5 x ULN.

Exclusion Criteria:

1. Subjects with acute promyelocytic leukemia (APL)
2. 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.
3. 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).
4. Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-90009.
5. Subjects on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD).
6. 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.
7. Leukapheresis ≤ 2 weeks prior to starting CC-90009.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CC-90009 - Part A; Will be administered intravenously per dosing schedule in a 28-day cycle.	Drug: CC-90009; CC-90009
Experimental: 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	Drug: CC-90009; CC-90009

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicity (DLTs)	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.	From first dose to at least 28 days and up to 42 days post first dose (Up to 42 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-Tolerated Dose (NTD) of CC-90009	The NTD is defined as a dose level at which 2 or more of up to 6 evaluable participants in any dose cohort experience a DLT in Cycle 1 during dose escalation (Part A)	From first dose to at least 28 days and up to 42 days post first dose (Up to 42 days)
Maximum Tolerated Dose (MTD) of CC-90009	The MTD is defined as the last dose level(s) below the NTD with 0 or 1 out of 6 evaluable participants experiencing a DLT in Cycle 1 during dose escalation (part A).	From first dose to at least 28 days and up to 42 days post first dose (Up to 42 days)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Treatment-emergent adverse events (TEAEs) are defined as any AEs that begin on or after the start of study drug through 28 days after the last dose of study drug or serious AEs that are suspected of being related to study drug.	From first dose until 28 days post last dose (Up to 25 months)
Change From Baseline by Laboratory Test - Chemistry Parameters 1	Change from baseline for chemistry laboratory parameters. Baseline = last value before start of treatment	From baseline until 28 days post last dose (Up to 25 months)
Change From Baseline by Laboratory Test - Chemistry Parameters 2	Change from baseline for chemistry laboratory parameters. Baseline = last value before start of treatment	From baseline until 28 days post last dose (Up to 25 months)
Change From Baseline by Laboratory Test - Chemistry Parameters 3	Change from baseline for chemistry laboratory parameters. Baseline = last value before start of treatment	From baseline until 28 days post last dose (Up to 25 months)
Change From Baseline for Vital Signs by Test - Parameters 1	Change from Baseline for Vital Signs Parameters. Baseline = last value before start of treatment.	From baseline until 28 days post last dose (Up to 25 months)
Change From Baseline for Vital Signs by Test - Parameters 2	Change from Baseline for Vital Signs Parameters. Baseline = last value before start of treatment.	From baseline until 28 days post last dose (Up to 25 months)
Change From Baseline for Vital Signs by Test - Parameters 3	Change from Baseline for Vital Signs Parameters. Baseline = last value before start of treatment.	From baseline until 28 days post last dose (Up to 25 months)
Change From Baseline for Vital Signs by Test - Parameters 4	Change from Baseline for Vital Signs Parameters. Baseline = last value before start of treatment.	From baseline until 28 days post last dose (Up to 25 months)
Change From Baseline for Electrocardiogram (ECG) by Test - Parameters 1	Change from Baseline for Electrocardiogram (ECG) Parameters. Baseline = last value before start of treatment.	From baseline until 28 days post last dose (Up to 25 months)
Change From Baseline for Electrocardiogram (ECG) by Test - Parameters 2	Change from Baseline for Electrocardiogram (ECG) Parameters. Baseline = last value before start of treatment.	From baseline until 28 days post last dose (Up to 25 months)
Eastern Cooperative Oncology Group (ECOG) Performance Status	Number of participants with post-baseline grade increase or decrease from baseline. Grade 0=; Grade 1=; Grade 2=; Grade 3=; Grade 4=; Grade 5=; . Baseline = last value before start of treatment.	From baseline until 28 days post last dose (Up to 25 months)
Left Ventricular Ejection Fraction (LVEF) Percent Change From Baseline	Left Ventricular Ejection Fraction (LVEF) percent change from baseline. Baseline = last value before start of treatment. Minimum Post Baseline Value=lowest value of the measured parameter is recorded after the baseline measurement. Maximum Post Baseline Value=highest value of the measured parameter is recorded after the baseline measurement.	From baseline until 28 days post last dose (Up to 25 months)
Objective Response Rate (ORR)	Objectve response is defined as the percent of participants whose best overall response is any type of Morphologic Complete Remission [CR] (CR, Morphologic Complete Remission with Incomplete Blood Count Recovery (CRi), Morphologic Complete Remission with Partial Hematologic Recovery (CRh), Cytogenetic Complete Remission (CRc) and Molecular Complete Remission (CRm)) or Morphologic Leukemia - Free State or partial remission. CR=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%; CRi=residual neutropenia < 1,000/μL, thrombocytopenia < 100,000/μL. CRh=neutrophils ≥ 500μL, platelets ≥500,000μL, blasts <5%; CRc=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%; cytogenetics normal; CRm=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%, negative EMD; PR=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts decrease in ≥ 50 resulting in 5 to 25%.	Up to approximately 25 months after the last dose
Overall Survival (OS)	OS is defined as the time from the date of the first dose to the date of death from any cause.	Up to approximately 25 months after the last dose
Relapse-free Survival (RFS)	RFS is defined only for participants who achieved CR or CRi (for AML) / CR or PR (for MDS) and is measured as the interval from the date of first CR or CRi (for AML) / CR or PR (for MDS) to the date of relapse or death from any cause, whichever occurs first. CR=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%; CRi=residual neutropenia < 1,000 μL, thrombocytopenia < 100,000/μL. PR=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts decrease in ≥ 50 resulting in 5 to 25%.	Up to approximately 25 months after the last dose
Progression-free Survival (PFS)	PFS is defined as the time from the date of the first dose to the date of first relapse after CR/CRi (for AML)/relapse after CR/PR(for MDS), or PD, or death resulting from any cause, whichever occurs first. CR=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%; CRi=residual neutropenia < 1,000 μL, thrombocytopenia < 100,000/μL. PR=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts decrease in ≥ 50 resulting in 5 to 25%. PD=At least 50% decrement from maximum remission/response levels in granulocytes or platelets; Reduction in Hgb concentration by ≥ 2 g/dL; Transfusion dependence. Based on Kaplan-Meier Estimates.	Up to approximately 25 months after the last dose
Event-free Survival (EFS)	EFS is defined as the interval from the date of the first dose to an event including disease progression (PD), treatment failure, relapse, or death from any cause, whichever occurs first. PD=At least 50% decrement from maximum remission/response levels in granulocytes or platelets; Reduction in Hgb concentration by ≥ 2 g/dL; Transfusion dependence. Based on Kaplan-Meier Estimates.	Up to approximately 25 months after the last dose
Duration of Remission/Response (DOR)	DOR is defined as the time from first remission/response observed to the date of relapse, death or PD. PD=At least 50% decrement from maximum remission/response levels in granulocytes or platelets; Reduction in Hgb concentration by ≥ 2 g/dL; Transfusion dependence. Based on Kaplan-Meier Estimates.	Up to approximately 25 months after the last dose
Time to Remission/Response (TTR)	TTR is defined as the time between the date of first dose and the earliest date any remission/response (any complete remissions or partial remissions or better) is observed. CR=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%; CRi=residual neutropenia < 1,000 μL, thrombocytopenia < 100,000/μL. CRh=neutrophils ≥ 500μL, platelets ≥500,000μL, blasts <5%; CRc=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%; cytogenetics normal; CRm=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%, negative EMD; PR=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts decrease in ≥ 50 resulting in 5 to 25%. Based on Kaplan-Meier Estimates.	Up to approximately 25 months after the last dose
Complete Remission Rate (CRR)	The complete remission rate (CRR) is defined as the percent of participants whose best overall response is any type of Morphologic Complete Remission [CR] (CR, Morphologic Complete Remission with Incomplete Blood Count Recovery (CRi), Morphologic Complete Remission with Partial Hematologic Recovery (CRh), Cytogenetic Complete Remission (CRc) and Molecular Complete Remission (CRm)). CR=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%; CRi=residual neutropenia < 1,000/μL, thrombocytopenia < 100,000/μL. CRh=neutrophils ≥ 500μL, platelets ≥500,000μL, blasts <5%; CRc=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%; cytogenetics normal; CRm=neutrophils ≥ 1,000μL, platelets ≥100,000μL, blasts <5%, negative EMD.	Up to approximately 88 months
Time to Acute Myeloid Leukemia (AML) Transformation	Time to acute AML transformation in part B Myelodysplastic Syndromes (MDS) participants only. Based on Kaplan-Meier Estimates.	Up to approximately 88 months
Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration, obtained directly from the observed concentration versus time data	Cycle 1 Day 1(C1D1), C1D5, C1D7, C1D8, C1D10,
Time to Peak Plasma Concentration (Tmax)	Time to peak plasma concentration, obtained directly from the observed concentration versus time data.	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)	Area under the plasma concentration-time curve from Time 0 to 24 hours post-dose.	Cycle 1 Day 1(C1D1), C1D5, C1D7, C1D8, C1D10. 1 cycle = 28 days
Terminal Phase Elimination Half-life (T1/2)	Terminal phase elimination half-life calculated as [(ln 2)/λz], where λz is the apparent terminal rate constant. t1/2 will only be calculated when a reliable estimate for λz can be obtained.	Cycle 1 Day 1(C1D1) and C1D5. 1 cycle = 28 days
Total Body Clearance (CL)	Total plasma clearance after IV administration, calculated as [Dose/ AUC(INF)] following single administration, and [Dose/ AUC(0-24)] at steady state.	Cycle 1 Day 1(C1D1), C1D5, C1D7, C1D8, C1D10. 1 cycle = 28 days
Volume of Distribution (Vz)	Volume of distribution calculated at first dose only. Calculated as [Vz = Dose/ AUC(INF) * λz for Day 1].	Cycle 1 Day 1(C1D1) and C1D5. 1 cycle = 28 days
Renal Clearance (CLr)	Renal clearance of CC-90009 (CLr)	Cycle 1 Day 1(C1D1). 1 cycle = 28 days

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Surka C, Jin L, Mbong N, Lu CC, Jang IS, Rychak E, Mendy D, Clayton T, Tindall E, Hsu C, Fontanillo C, Tran E, Contreras A, Ng SWK, Matyskiela M, Wang K, Chamberlain P, Cathers B, Carmichael J, Hansen J, Wang JCY, Minden MD, Fan J, Pierce DW, Pourdehnad M, Rolfe M, Lopez-Girona A, Dick JE, Lu G. CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells. Blood. 2021 Feb 4;137(5):661-677. doi: 10.1182/blood.2020008676.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2016
• Primary Completion (Actual): April 11, 2023
• Study Completion (Actual): April 11, 2024

Study Registration Dates

• First Submitted: June 22, 2016
• First Submitted That Met QC Criteria: July 25, 2016
• First Posted (Estimated): July 28, 2016

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; AML; Leukemia; MDS; CC-90009; Hematologic Cancers; Myelodysplastic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Syndrome; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes
• Other Study ID Numbers: CC-90009-AML-001; 2017-001535-39 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No