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

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ClinicalTrials.gov Identifier: NCT02848001
Recruitment Status : Recruiting
First Posted : July 28, 2016
Last Update Posted : July 22, 2021
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE June 22, 2016
First Posted Date  ICMJE July 28, 2016
Last Update Posted Date July 22, 2021
Actual Study Start Date  ICMJE November 14, 2016
Estimated Primary Completion Date August 25, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 25, 2016)
  • Dose- limiting toxicity (DLT) [ Time Frame: Up to 42 days ]
    Number of participants with a DLT
  • Non-tolerated dose (NTD) [ Time Frame: Up to 42 days ]
    Dose level at which 2 or more of up to 6 evaluable subjects in any dose cohort experience a DLT in Cycle 1 during dose escalation.
  • Maximum tolerated dose (MTD) [ Time Frame: Up to 42 days ]
    Last dose level(s) below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT in Cycle 1 during dose escalation
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2018)
  • Pharmacokinetics-Cmax [ Time Frame: Up to Day 11 ]
    Maximum observed concentration in plasma
  • Pharmacokinetics - AUC24 [ Time Frame: Up to Day 11 ]
    Area under the plasma concentration time-curve from time 0 to 24 hours
  • Pharmacokinetics - tmax [ Time Frame: Up to Day 11 ]
    Time to peak (maximum) plasma concentration
  • Pharmacokinetics - t 1/2 [ Time Frame: Up to Day 11 ]
    terminal half-life
  • Pharmacokinetics - CL [ Time Frame: Up to Day 11 ]
    Total body clearance of the drug from plasma
  • Pharmacokinetics - Vss [ Time Frame: Up to Day 11 ]
    Volume of distribution at steady-state
  • Preliminary efficacy of CC-90009 [ Time Frame: Up to 2.5 years ]
    Determined by acute myeloid leukemia (AML) response rate based on the International Working Group (IWG) Response Criteria in AML (Cheson, 2003)
  • Preliminary efficacy of CC-90009 - AML [ Time Frame: Up to 2.5 years ]
    Determined by acute myeloid leukemia (AML) response rate based on the International Working Group (IWG) Response Criteria in AML.
  • Preliminary efficacy of CC-90009 - MDS [ Time Frame: Up to 2.5 years ]
    Determined by myelodysplastic syndrome (MDS) response rate based on the International Working Group (IWG) response criteria for Myelodysplasia.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2016)
  • Pharmacokinetics-Cmax [ Time Frame: Up to Day 6 ]
    Maximum observed concentration in plasma
  • Pharmacokinetics - AUC [ Time Frame: Up to Day 6 ]
    Area under the plasma concentration - time curve
  • Pharmacokinetics - tmax [ Time Frame: Up to Day 6 ]
    Time to peak (maximum) plasma concentration
  • Pharmacokinetics - t 1/2 [ Time Frame: Up to Day 6 ]
    terminal half-life
  • Pharmacokinetics - CL [ Time Frame: Up to Day 6 ]
    Total body clearance of the drug from plasma
  • Pharmacokinetics - Vmax [ Time Frame: Up to Day 6 ]
    Volume of distribution at steady-state
  • Preliminary efficacy of CC-90009 [ Time Frame: Up to 2.5 years ]
    Determined by acute myeloid leukemia (AML) response rate based on the International Working Group (IWG) Response Criteria in AML (Cheson, 2003)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose-finding Study of CC-90009 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-risk Myelodysplastic Syndromes
Official Title  ICMJE 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
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 high-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 high-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 high-risk myelodysplastic syndrome.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndromes
Intervention  ICMJE Drug: CC-90009
CC-90009
Study Arms  ICMJE
  • Experimental: CC-90009 - Part A
    Will be administered intravenously per dosing schedule in a 28-day cycle.
    Intervention: Drug: 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
    Intervention: Drug: CC-90009
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 9, 2021)
110
Original Estimated Enrollment  ICMJE
 (submitted: July 25, 2016)
60
Estimated Study Completion Date  ICMJE February 26, 2022
Estimated Primary Completion Date August 25, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 high-risk MDS (Myelodysplastic Syndrome) (Part B only) as defined by World Health Organization criteria who are not suitable for other established therapies.
  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:

    • Total White Blood Cell count (WBC) < 25 x 109/L prior to first infusion. Prior or concurrent treatment with hydroxyurea to achieve this level is 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.
  7. Agree to follow the CC-90009 Pregnancy Prevention Plan (PPP)

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). The use of topical steroids for ongoing skin or ocular GVHD is permitted.
  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.
  8. For Part B, previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.
  9. For Part B, previous COVID-19 vaccine within 14 days of C1D1.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT # and Site #.
Listed Location Countries  ICMJE Canada,   France,   Norway,   Spain,   United Kingdom,   United States
Removed Location Countries Italy
 
Administrative Information
NCT Number  ICMJE NCT02848001
Other Study ID Numbers  ICMJE CC-90009-AML-001
2017-001535-39 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: August Dietrich, MD Celgene
PRS Account Celgene
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP