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

NCT ID: NCT02848001

Last Updated: 2025-06-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-14
• Study Completion Date: 2024-04-11

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.

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.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CC-90009 - Part A

Will be administered intravenously per dosing schedule in a 28-day cycle.

Group Type: EXPERIMENTAL

CC-90009

Intervention Type: DRUG

CC-90009

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

Group Type: EXPERIMENTAL

CC-90009

Intervention Type: DRUG

CC-90009

Interventions

CC-90009

CC-90009

Intervention Type: DRUG

Eligibility 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.

• 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

Stanford Cancer Center

Stanford, California, United States

Local Institution - 105

New Haven, Connecticut, United States

Local Institution - 102

Chicago, Illinois, United States

Local Institution - 103

Boston, Massachusetts, United States

Local Institution - 101

St Louis, Missouri, United States

Local Institution - 104

Hackensack, New Jersey, United States

Local Institution - 201

Toronto, Ontario, Canada

Local Institution - 505

Lillie Cedex, , France

Institut Paoli Calmettes

Marseille, , France

Hopital Lyon Sud

Pierre-Bénite, , France

Local Institution - 502

Toulouse, , France

Local Institution - 700

Bergen, , Norway

Local Institution - 701

Oslo, , Norway

Local Institution - 603

Badalona, , Spain

Local Institution - 602

Barcelona, , Spain

Local Institution - 604

Madrid, , Spain

Local Institution - 605

Pamplona, , Spain

Local Institution - 601

Salamanca, , Spain

Local Institution - 600

Valencia, , Spain

Local Institution - 301

Oxford, , United Kingdom

Countries

United States; Canada; France; Norway; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33197925 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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

BMS Clinical Trial Information

http://www.BMSClinicalTrials.com

BMS Clinical Trial Patient Recruiting

Other Identifiers

2017-001535-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-90009-AML-001

Identifier Type: -

Identifier Source: org_study_id