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A Safety, Tolerability and Preliminary Efficacy Study of CC-90011 in Combination With Venetoclax and Azacitidine in R/R Acute Myeloid Leukemia and Treatment-naïve Participants Not Eligible for Intensive Therapy

NCT04748848

Description:

CC-90011-AML-002 is a Phase 1/2, open-label, multicenter study to assess the safety, tolerability, and preliminary efficacy of CC-90011 given concurrently with Venetoclax and Azacitidine. This study will include 3 parts: a dose escalation part in R/R AML, a dose escalation part in ndAML (treatment-naïve participants with AML who are ≥ 75 years of age or are ≥ 18 to 74 years of age and otherwise not eligible for intensive induction chemotherapy), and a randomized dose expansion part in ndAML of Venetoclax and Azacitidine with or without CC-90011.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Safety, Tolerability and Preliminary Efficacy Study of CC-90011 in Combination With Venetoclax and Azacitidine in R/R Acute Myeloid Leukemia and Treatment-naïve Participants Not Eligible for Intensive Therapy
  • Official Title: A Phase 1/2, Open-label, Multicenter Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of CC-90011 in Combination With Venetoclax and Azacitidine in R/R Acute Myeloid Leukemia (AML) and Treatment-Naïve Subjects With AML Who Are Not Eligible for Intensive Induction Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: CC-90011-AML-002
  • SECONDARY ID: U1111-1251-6973
  • SECONDARY ID: 2020-005341-16
  • NCT ID: NCT04748848

Conditions

  • Leukemia, Myeloid

Interventions

DrugSynonymsArms
CC-90011CC-90011 in combination with Venetoclax and Azacitidine in Dose Escalation
VenetoclaxCC-90011 in combination with Venetoclax and Azacitidine in Dose Escalation
AzacitidineCC-90011 in combination with Venetoclax and Azacitidine in Dose Escalation
VenetoclaxVenetoclax and Azacitidine
CC-90011CC-90011 in combination with Venetoclax and Azacitidine in Dose Expansion

Purpose

CC-90011-AML-002 is a Phase 1/2, open-label, multicenter study to assess the safety, tolerability, and preliminary efficacy of CC-90011 given concurrently with Venetoclax and Azacitidine. This study will include 3 parts: a dose escalation part in R/R AML, a dose escalation part in ndAML (treatment-naïve participants with AML who are ≥ 75 years of age or are ≥ 18 to 74 years of age and otherwise not eligible for intensive induction chemotherapy), and a randomized dose expansion part in ndAML of Venetoclax and Azacitidine with or without CC-90011.

Trial Arms

NameTypeDescriptionInterventions
CC-90011 in combination with Venetoclax and Azacitidine in Dose EscalationExperimentalCC-90011 in combination with venetoclax and azacitidine in dose escalation
  • CC-90011
  • Venetoclax
  • Azacitidine
Venetoclax and AzacitidineExperimentalVenetoclax and Azacitidine control arm in dose expansion. The participants will be randomized to the treatment arm or control arm at a 2:1 ratio.
  • Azacitidine
  • Venetoclax
CC-90011 in combination with Venetoclax and Azacitidine in Dose ExpansionExperimentalCC-90011 in combination with venetoclax and azacitidine in dose expansion
  • Venetoclax
  • Azacitidine
  • CC-90011

Eligibility Criteria

        Inclusion Criteria:

        Participants must satisfy the following criteria to be enrolled in the study:

        All participants (Parts I, II, and III):

        1. Participant must understand and voluntarily sign an Informed Consent Form (ICF) prior to
        any study-related assessments/procedures being conducted.

        3. Participant must have a projected life expectancy of at least 12 weeks. 4. Participant
        has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

        5. Participants must have the required protocol baseline laboratory values 6. Participant
        has adequate organ function 7. Participant must be able and willing to undergo
        hospitalization, hydration, and treatment with a uric acid-reducing agent prior to the
        first dose of venetoclax and during Cycle 1.

        Part I only:

        8. Relapsed and/or refractory acute myeloid leukemia (AML) as defined by the World Health
        Organization (WHO) Classification and is ≥ 18 years of age at the time of signing the ICF
        who are not eligible to receive further intensive therapy and:

          1. Has failed to have a complete remission (CR) or CR with incomplete hematologic
             recovery (Cri) after induction plus reinduction with intensive chemotherapy
             (anthracycline plus cytarabine containing regimens) or 2 cycles of low intensity
             therapy (either 2 cycles of the same regimen or 1 cycle of 2 different regimens) OR

          2. Has relapsed from CR from either intensive or low-intensity therapy. Participants with
             second relapse are also eligible

        Part II and Part III only:

        9. Histologically confirmed treatment naïve Acute myeloid leukemia (AML) as defined by the
        2008 World Health Organization (WHO) Classification, including secondary AML and therapy
        related AML, and is ≥ 75 years of age at the time of signing the ICF, or is ≥ 18 to 74
        years at the time of signing the ICF with comorbidities precluding the use of intensive
        induction chemotherapy 10. Participant has not received prior therapy for AML with the
        exception of hydroxyurea to treat hyperleukocytosis.

        Exclusion Criteria:

        The presence of any of the following will exclude a participant from enrollment:

        All participants (Parts I, II, and III):

          1. Participant is suspected or proven to have acute promyelocytic leukemia (APL) based on
             morphology, immunophenotype, molecular assay, or karyotype.

          2. Participant has favorable risk cytogenetics

          3. Participants with AML who may receive fms-like tyrosine kinase 3 (FLT3) inhibitor
             directed therapy.

          4. Participant has or is suspected of having active central nervous system (CNS)
             involvement.

          5. Participant has an active, uncontrolled infection except participants with infection
             under active treatment and controlled with antibiotics, antifungals, or antivirals are
             eligible.

          6. Participant with prior autologous hematopoietic stem cell transplant (HSCT) who, in
             the investigator's judgment, have not fully recovered from the effects of the last
             transplant (eg, transplant related side effects).

          7. Participant had prior allogeneic HSCT with either standard or reduced intensity
             conditioning ≤ 6 months prior to dosing.

          8. Participants 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.

          9. Participant has immediate life-threatening, severe complications of leukemia such as
             disseminated/uncontrolled infection, uncontrolled bleeding, pneumonia with hypoxia or
             shock, and/or disseminated intravascular coagulation. The participant should be
             afebrile for at least 72 hours.

         10. Participants requiring treatment with strong or moderate CYP3A inhibitors/inducers.

         11. Participant has ongoing treatment with chronic, therapeutic dosing of anticoagulants.

         12. Participant has a history of concurrent secondary cancers requiring active, ongoing
             systemic treatment.

         13. Participant has known human immunodeficiency virus (HIV) infection.

         14. Participant has known chronic active hepatitis B virus (HBV) or hepatitis C virus
             (HCV).

               1. Participant who is seropositive due to HBV vaccination is eligible.

               2. Participant who has no active viral infection and is under adequate prophylaxis
                  against HBV reactivation is eligible.

         15. Participant is known to have dysphagia, short-gut syndrome, gastroparesis, or other
             conditions that limit the ingestion or gastrointestinal absorption of drugs
             administered orally.

         16. Participant has impaired cardiac function or clinically significant cardiac diseases

         17. Participant has consumed grapefruit, grapefruit products, Seville oranges (including
             marmalade containing Seville oranges), or Star fruit within 3 days prior to first
             venetoclax dose through last dose of venetoclax.

         18. Pregnant women are excluded from this study due to potential teratogenic and/or
             abortifacient effect of this therapy. Nursing mothers should stop breastfeeding in
             order to be eligible due to potential risk for Adverse Events (AEs) in a nursing
             infant.

         19. Participant has had previous treatment with a lysine-specific demethylase 1A (LSD1)
             inhibitor.

         20. Participant has any significant medical condition, laboratory abnormality, or
             psychiatric illness that would prevent the participant from participating in the
             study.

         21. Participant has any condition including the presence of laboratory abnormalities,
             which places the participant at unacceptable risk if he/she were to participate in the
             study.

         22. Participant has any condition that confounds the ability to interpret data from the
             study.

         23. Participants currently in other interventional trials, including those for COVID-19,
             may not participate in BMS clinical trials until the protocol specific washout period
             is achieved. If a study participant has received an investigational COVID-19 vaccine
             or other investigational product designed to treat or prevent COVID-19 prior to
             screening, enrollment must be delayed until the biologic impact of the vaccine or
             investigational product is stabilized, as determined by discussion between the
             Investigator and the Medical Monitor.

             Part I only:

         24. Participant had prior treatment with venetoclax for AML, either as monotherapy or in
             combination with other agents.

             Part II and Part III only:

         25. Participant had prior treatment with hypomethylating agent (HMA) or chemotherapy for
             antecedent hematologic disorders. Prior treatment with hydroxyurea is permitted.

         26. Participant has received systemic anticancer therapy (including investigational
             therapy), radiotherapy, or immunotherapy < 14 days or 5 half-lives, whichever is
             shorter, prior to the first dose of CC-90011.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:From ICF signature until 28 days after last dose of CC- 90011
Safety Issue:
Description:An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE

Secondary Outcome Measures

Measure:Complete remission (CR) Rate
Time Frame:Up to approximately 10 months
Safety Issue:
Description:Defined as the rate of achieving CR (as assessed by the Investigator and by programmatic outputs by the Sponsor)
Measure:Complete remission with partial hematologic recovery (CRh) Rate
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Defined as the rate of achieving CRh (as assessed by the Investigator and by programmatic outputs by the Sponsor)
Measure:Overall response rate (ORR)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Defined as the rate of achieving CR/CRMRD-/CRi/PR/MLFS
Measure:Duration of CR
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Time from the first CR to the date of documented disease relapse or death, whichever is earlier.
Measure:Duration of CR/CRh
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Time from the first CR or CRh to the date of documented disease relapse or death, whichever is earlier.
Measure:Duration of OR
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Time from the first CR, CRMRD-, CRi, PR or MLFS to the date of documented disease relapse, progression, or death, whichever is earlier.
Measure:Event-free survival (EFs)_Part III Only
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Time from study randomization to the date of treatment failure, relapse from CR or death from any cause, whichever comes first.
Measure:Overall survival (OS)_Part III Only
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Time from study randomization to the date of death due to any cause.
Measure:Minimal residual disease (MRD) Response Rate_Part II and III only
Time Frame:Up to approximately 2 years
Safety Issue:
Description:The rate of having at least a one log reduction in disease burden or an MRD negative (10-3) test result.
Measure:Minimal residual disease (MRD) Conversion Rate_Part II and III Only
Time Frame:Up to approximately 2 years
Safety Issue:
Description:The rate of participants achieving MRD negativity (10-3) at any time on therapy.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Acute Myeloid Leukemia
  • CC-90011
  • Venetoclax
  • Azacitidine
  • LSD-1 inhibitor
  • Minimal residual disease

Last Updated

February 10, 2021