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

NCT ID: NCT04748848

Last Updated: 2023-03-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-14
• Study Completion Date: 2022-03-09

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: EXPERIMENTAL

CC-90011

Intervention Type: 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.

Venetoclax

Intervention Type: 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.

Azacitidine

Intervention Type: 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

Venetoclax and Azacitidine

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.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: 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

Venetoclax

Intervention Type: DRUG

Venetoclax is administered orally QD on Days 1 to 28 of each 28-day cycle

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

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

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: 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.

Azacitidine

Intervention Type: 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

Intervention Type: DRUG

CC-90011 will be given PO on Days 1, 8, and 15 of continuous 4-week (28-day) cycle at the recommended phase to dose of CC-90011 confirmed in dose escalation.

Interventions

CC-90011

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.

Intervention Type: DRUG

Venetoclax

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.

Intervention Type: DRUG

Azacitidine

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

Intervention Type: DRUG

Venetoclax

Venetoclax is administered orally QD on Days 1 to 28 of each 28-day cycle

Intervention Type: DRUG

CC-90011

CC-90011 will be given PO on Days 1, 8, and 15 of continuous 4-week (28-day) cycle at the recommended phase to dose of CC-90011 confirmed in dose escalation.

Intervention Type: DRUG

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. Participant received live COVID-19 vaccines within 30 days prior to initiation of study treatment

24. 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:

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

Part II and Part III only:

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

27. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 110

Duarte, California, United States

Local Institution - 103

New Haven, Connecticut, United States

Local Institution - 108

Miami, Florida, United States

Local Institution - 111

Chicago, Illinois, United States

Local Institution - 121

New York, New York, United States

Local Institution - 118

Durham, North Carolina, United States

Local Institution - 116

Cleveland, Ohio, United States

Local Institution - 115

Columbus, Ohio, United States

Local Institution - 104

Dallas, Texas, United States

Local Institution - 101

Houston, Texas, United States

Local Institution - 120

Seattle, Washington, United States

Local Institution - 202

Ghent, , Belgium

Local Institution - 401

Villejuif, , France

Local Institution - 803

Barcelona, , Spain

Local Institution - 800

Barcelona, , Spain

Local Institution - 802

Madrid, , Spain

Local Institution - 801

Seville, , Spain

Countries

United States; Belgium; France; Spain

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsstudyconnect.com/s/US/English/USenHome

BMS Clinical Trial Patient Recruiting

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

FDA Safety Alerts and Recalls

Other Identifiers

U1111-1251-6973

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-005341-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-90011-AML-002

Identifier Type: -

Identifier Source: org_study_id