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 | Terminated Phase 1 FDA Drug

• 3 other identifiers: CC-90011-AML-002U1111-1251-69732020-005341-16
• Study Type: interventional
• Target: 1
• Locations: 4 countries
• Sites: 17

Brief Summary

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.

Conditions

Leukemia, Myeloid

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Adverse Events (AEs)

  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

  From ICF signature until 28 days after last dose of CC- 90011 and all combination agents

• Recommended Phase 2 dose (RP2D)

  The RP2D will include evaluation of DLTs and MTD using NCI CTCAE criteria

  Up to approximately Cycle 1 (each cycle is 28 days)

Secondary Outcomes (12)

• Complete remission (CR) Rate

  Up to approximately 10 months

• Complete remission with partial hematologic recovery (CRh) Rate

  Up to approximately 2 years

• Overall response rate (ORR)

  Up to approximately 2 years

• Duration of response (CR)

  Up to approximately 2 years

• Duration of response (CR/CRh)

  Up to approximately 2 years

Study Arms (3)

CC-90011 in combination with Venetoclax and Azacitidine in Dose Escalation

EXPERIMENTAL

CC-90011 in combination with venetoclax and azacitidine in dose escalation

Drug: CC-90011; Drug: Venetoclax; Drug: Azacitidine

Venetoclax and Azacitidine

EXPERIMENTAL

Venetoclax and Azacitidine control arm in dose expansion. The participants will be randomized to the treatment arm or control arm at a 2:1 ratio.

Drug: Azacitidine; Drug: Venetoclax

CC-90011 in combination with Venetoclax and Azacitidine in Dose Expansion

EXPERIMENTAL

CC-90011 in combination with venetoclax and azacitidine in dose expansion

Drug: Venetoclax; Drug: Azacitidine; Drug: CC-90011

Interventions

CC-90011 DRUG

CC-90011 will be given PO on Days 1, 8, and 15 of continuous 4-week (28-day) cycle. The dose escalation is designed to explore three dose levels of CC-90011, for example 20, 40, and 60 mg as determined by Bayesian design.

CC-90011 in combination with Venetoclax and Azacitidine in Dose Escalation

Azacitidine DRUG

Azacitidine is administered on Days 1 to 7 of each 28-day cycle as an IV infusion or SC injection at 75 mg/m2

CC-90011 in combination with Venetoclax and Azacitidine in Dose Escalation; CC-90011 in combination with Venetoclax and Azacitidine in Dose Expansion; Venetoclax and Azacitidine

Venetoclax DRUG

Venetoclax is administered orally QD on Days 1 to 28 of each 28-day cycle with a brief dose ramp-up for Cycle 1 with the dosing of 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3. Venetoclax should be administered at 400 mg on subsequent days.

CC-90011 in combination with Venetoclax and Azacitidine in Dose Escalation; CC-90011 in combination with Venetoclax and Azacitidine in Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must satisfy the following criteria to be enrolled in the study:
• All participants (Parts I, II, and III):
• \. Participant must understand and voluntarily sign an Informed Consent Form (ICF) prior to any study-related assessments/procedures being conducted.
• \. 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.
• \. 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:
• \. 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:
• 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
• Has relapsed from CR from either intensive or low-intensity therapy. Participants with second relapse are also eligible
• Part II and Part III only:
• \. 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.

You may not qualify if:

• The presence of any of the following will exclude a participant from enrollment:
• All participants (Parts I, II, and III):
• Participant is suspected or proven to have acute promyelocytic leukemia (APL) based on morphology, immunophenotype, molecular assay, or karyotype.
• Participant has favorable risk cytogenetics
• Participants with AML who may receive fms-like tyrosine kinase 3 (FLT3) inhibitor directed therapy.
• Participant has or is suspected of having active central nervous system (CNS) involvement.
• Participant has an active, uncontrolled infection except participants with infection under active treatment and controlled with antibiotics, antifungals, or antivirals are eligible.
• 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).
• Participant had prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing.
• 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.
• 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.
• Participants requiring treatment with strong or moderate CYP3A inhibitors/inducers.
• Participant has ongoing treatment with chronic, therapeutic dosing of anticoagulants.
• Participant has a history of concurrent secondary cancers requiring active, ongoing systemic treatment.
• Participant has known human immunodeficiency virus (HIV) infection.

Sponsors & Collaborators

• Celgene: lead

Study Sites (17)

Local Institution - 110

Duarte, California, 91010-301, United States

Location

Local Institution - 103

New Haven, Connecticut, 06510, United States

Location

Local Institution - 108

Miami, Florida, 33136, United States

Location

Local Institution - 111

Chicago, Illinois, 60611, United States

Location

Local Institution - 121

New York, New York, 10029, United States

Location

Local Institution - 118

Durham, North Carolina, 27710, United States

Location

Local Institution - 116

Cleveland, Ohio, 44195, United States

Location

Local Institution - 115

Columbus, Ohio, 43210, United States

Location

Local Institution - 104

Dallas, Texas, 75246, United States

Location

Local Institution - 101

Houston, Texas, 77030, United States

Location

Local Institution - 120

Seattle, Washington, 98104, United States

Location

Local Institution - 202

Ghent, 9000, Belgium

Location

Local Institution - 401

Villejuif, 94805, France

Location

Local Institution - 803

Barcelona, 08035, Spain

Location

Local Institution - 800

Barcelona, 08907, Spain

Location

Local Institution - 802

Madrid, 28007, Spain

Location

Local Institution - 801

Seville, 41013, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasm, Residual

Interventions

pulrodemstat besilate; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2021
• First Posted: February 10, 2021
• Study Start: October 14, 2021
• Primary Completion: March 9, 2022
• Study Completion: March 9, 2022
• Last Updated: March 2, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (11); FR (1); ES (4); BE (1)