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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02848001
Recruitment Status : Active, not recruiting
First Posted : July 28, 2016
Last Update Posted : April 28, 2023
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Description
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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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Myelodysplastic Syndromes Drug: CC-90009 Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 14, 2016
Actual Primary Completion Date : April 11, 2023
Estimated Study Completion Date : July 13, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Dose- limiting toxicity (DLT) [ Time Frame: Up to 42 days ]
    Number of participants with a DLT

  2. 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.

  3. 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

  4. Number of participants with Adverse Events (AEs) [ Time Frame: Up to 42 days ]
  5. Number of participants with laboratory abnormalities [ Time Frame: Up to 42 days ]
  6. Number of participants with vital sign abnormalities [ Time Frame: Up to 42 days ]
  7. Number of participants with electrocardiogram (ECG) abnormalities [ Time Frame: Up to 42 days ]
  8. Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities [ Time Frame: Up to 42 days ]
  9. Number of participants with Left Ventricle Ejection Fraction (LVEF) assessment abnormalities [ Time Frame: Up to 42 days ]
  10. Number of participants with physical examination abnormalities [ Time Frame: Up to 42 days ]

Secondary Outcome Measures :
  1. Preliminary efficacy of CC-90009 - acute myeloid leukemia (AML) [ Time Frame: Up to 2.5 years ]
    Determined by response rates of AML by disease response criteria

  2. Overall survival [ Time Frame: Up to 2.5 years ]
  3. Relapse-free survival [ Time Frame: Up to 2.5 years ]
  4. Progression-free survival [ Time Frame: Up to 2.5 years ]
  5. Event-free survival [ Time Frame: Up to 2.5 years ]
  6. Duration of remission [ Time Frame: Up to 2.5 years ]
  7. Duration of response [ Time Frame: Up to 2.5 years ]
  8. Time to remission for AML participants [ Time Frame: Up to 2.5 years ]
  9. Time to response for AML participants [ Time Frame: Up to 2.5 years ]
  10. Preliminary efficacy of CC-90009 - Higher-risk myelodysplastic syndromes (HR-MDS) [ Time Frame: Up to 2.5 years ]
    Determined by response rates of HR-MDS by disease response criteria

  11. Time to AML transformation [ Time Frame: Up to 2.5 years ]
  12. Time to remission for HR-MDS participants [ Time Frame: Up to 2.5 years ]
  13. Time to response for HR-MDS participants [ Time Frame: Up to 2.5 years ]
  14. Pharmacokinetics-Cmax [ Time Frame: Up to Day 11 ]
    Maximum observed concentration in plasma

  15. Pharmacokinetics - AUC24 [ Time Frame: Up to Day 11 ]
    Area under the plasma concentration time-curve from time 0 to 24 hours

  16. Pharmacokinetics - tmax [ Time Frame: Up to Day 11 ]
    Time to peak (maximum) plasma concentration

  17. Pharmacokinetics - t 1/2 [ Time Frame: Up to Day 11 ]
    terminal half-life

  18. Pharmacokinetics - CL [ Time Frame: Up to Day 11 ]
    Total body clearance of the drug from plasma

  19. Pharmacokinetics - Vss [ Time Frame: Up to Day 11 ]
    Volume of distribution at steady-state


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02848001


Locations
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Sponsors and Collaborators
Celgene
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02848001    
Other Study ID Numbers: CC-90009-AML-001
2017-001535-39 ( EudraCT Number )
First Posted: July 28, 2016    Key Record Dates
Last Update Posted: April 28, 2023
Last Verified: April 2023
Keywords provided by Celgene:
CC-90009
Hematologic Cancers
Leukemia
Acute Myeloid Leukemia
 Myelodysplastic Syndrome
AML
MDS
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
 Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions