A Safety and Efficacy Study of CC-90009 Combinations in Subjects With Acute Myeloid Leukemia

Sponsor
Celgene (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04336982
Collaborator
AbbVie (Industry)
43
21
2
53.7
2
0

Study Details

Study Description

Brief Summary

CC-90009-AML-002 is an exploratory Phase 1b, open-label, multi-arm trial to evaluate the safety and efficacy of CC-90009 in combination with anti-leukemia agents in participants with acute myeloid leukemia (AML).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Study CC-90009-AML-002 is an open-label, multi-arm, parallel multi-cohort, multicenter, Phase 1b study to determine the safety, tolerability, PK, and efficacy of CC 90009 in combination with anti-leukemia agents used for the treatment of AML. CC 90009 will be given as a combination therapy to subjects with newly diagnosed (ND) or relapsed or refractory (R/R) AML.

The dose and schedule finding part (Part A) of the study will evaluate the safety, PK and PD data, and preliminary efficacy information and determine the Part B dose and schedule for each arm.

The expansion part (Part B) of the study will further evaluate the safety and efficacy of the CC-90009 containing combination at or below the maximum tolerated dose (MTD) in the selected cohorts in order to determine the recommended Phase 2 dose (RP2D) for subjects with AML.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
43 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Exploratory Phase 1b Open-label Multi-arm Trial to Evaluate the Safety and Efficacy of CC-90009 in Combination With Anti-Leukemia Agents in Subjects With Acute Myeloid Leukemia
Actual Study Start Date :
Aug 5, 2020
Anticipated Primary Completion Date :
Jan 25, 2025
Anticipated Study Completion Date :
Jan 25, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: CC-90009 in combination with venetoclax and azacitidine

CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Venetoclax will be administered orally QD. Azacitidine will be administered intravenously or subcutaneously on planned dosing days for each cycle.

Drug: CC-90009
Injection

Drug: Venetoclax
Tablet

Drug: Azacitidine
Injection

Experimental: CC-90009 in combination with gilteritinib

CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Gilteritinib will be administered orally QD.

Drug: Gilteritinib
Tablet

Outcome Measures

Primary Outcome Measures

  1. Dose Limiting Toxicity (DLT) [Up to 28 days]

    Number of participants with a DLT

  2. Adverse Events (AEs) [Up to 28 days after last dose of study drug.]

    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject 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 subject's health, including laboratory test values, regardless of etiology.

Secondary Outcome Measures

  1. Complete Remission Rate (CRR), [Up to 3 years]

    is defined as the rate for any type of CR or CRh

  2. Objective Response Rate (ORR) [Up to 3 years]

    includes all responses of complete remissions (CRs), Morphologic leukemia-free state (MLFS), and Partial remission (PR)

  3. Progression Free Survival (PFS) [Up to 3 years]

    is defined as the time from the first dose of study drug(s) to the first occurrence of relapse or progression or death from any cause

  4. Overall Survival (OS) [Up to 3 years]

    is measured as the time from the first dose of study drug(s) to death due to any cause and will be analyzed in a manner similar to that described for PFS.

  5. Duration of Remission [Up to 3 years]

    is measured from the time when criteria for CR/CRh/PR are first met (whichever is first recorded) until the first date at which relapse, or progressive disease is objectively documented.

  6. Time to Remission [Up to 3 years]

    is measured from the time when criteria for CR/CRh/PR are first met (whichever is first recorded)

  7. Pharmacokinetics - Cmax [Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)]

    observed maximum concentration in plasma

  8. Pharmacokinetics - AUC24 [Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)]

    area under the plasma concentration time-curve from time 0 to 24 hours postdose

  9. Pharmacokinetics - t1/2 [Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)]

    terminal half life

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Adult subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.

  2. Arm A (CC-90009 + venetoclax/azacitidine):

  3. Part A: Newly diagnosed AML with poor/adverse risk genetic abnormalities and is ≥ 75 years of age or intensive chemotherapy ineligible OR

  4. Part A: Refractory AML and is ≥ 18 years of age

  5. Part B: Newly diagnosed AML and is ≥ 75 years of age or intensive chemotherapy ineligible

  6. Arm B (CC-90009 + gilteritinib):

  7. Subject is ≥ 18 years of age.

  8. Fms-like tyrosine kinase 3 (FLT3) mutation positive.

  9. Gilteritinib treatment naïve

  10. Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

  11. Subject must have the following screening laboratory values:

  • Total White Blood Cell count (WBC) < 25 x 10^9/L prior to study treatments. Treatment with hydroxyurea to achieve this level is allowed.

  • Selected electrolytes within normal limits or correctable with supplements.

  • Participant must have adequate liver function as demonstrated by: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) and bilirubin ≤ 1.5 x ULN

  • Participant has adequate renal function as demonstrated by an estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation.

  1. Agree to follow the CC-90009 Pregnancy Prevention Plan (PPP) and combination agents' requirements.
Exclusion Criteria:
  1. Subject with acute promyelocytic leukemia (APL)

  2. Subject has received systemic anticancer therapy (including investigational therapy) or radiotherapy < 28 days or 5 half-lives, whichever is shorter, prior to the start of study treatment

  3. Patients 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)

  4. Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing

  5. Subject 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

  6. Subject has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2

  7. Subject has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening.

  8. Disorders or conditions disrupting normal calcium homeostasis or preventing calcium supplementation.

  9. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

  10. Left ventricular ejection fraction (LVEF) < 45% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).

  11. Complete left bundle branch or bifascicular block.

  12. Congenital long QT syndrome.

  13. Persistent or clinically meaningful ventricular arrhythmias.

  14. QTcF ≥ 470 ms (Arm A) or > 450 ms (Arm B) on Screening electrocardiogram (ECG)

  15. Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting study treatments or unstable arrhythmia.

  16. Cardiovascular disability status of New York Heart Association Class ≥2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.

  17. Subject is a pregnant or lactating female

  18. Additional exclusion criteria based on combination agent:

  1. For Combination Arm A (venetoclax/azacitidine):
  • Received strong or moderate CYP3A inhibitors or inducers or P-gp inhibitors within 7 days prior to initiation of first venetoclax dose.

  • Subject 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.

  1. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.
  1. Acute symptoms must have resolved and based on investigator assessment in consultation with the medical monitor, there are no sequelae that would place the participant at a higher risk of receiving study treatment.
  1. Previous SARS-CoV-2 vaccine within 14 days of C1D1.

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of California, San Francisco San Francisco California United States 94143-0324
2 University Of California, San Francisco San Francisco California United States 94143-0324
3 Yale New Haven Hospital New Haven Connecticut United States 06510
4 Dana-Farber/Mass General Brigham Cancer Care, Inc Boston Massachusetts United States 02115
5 Washington University School of Medicine Saint Louis Missouri United States 63110
6 Washington University School Of Medicine Saint Louis Missouri United States 63110
7 Hackensack University Medical Center Hackensack New Jersey United States 07601
8 The University of Texas - MD Anderson Cancer Center Houston Texas United States 77030
9 The University of Texas - MD Anderson Cancer Center Houston Texas United States 77030
10 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109-1024
11 University of Alberta Edmonton Alberta Canada T6G 2R7
12 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
13 Hopital Maisonneuve-Rosemont Montreal Quebec Canada H1T 2M4
14 Institut Paoli-Calmettes Marseille France 13273
15 Local Institution - 402 Marseille France 13273
16 Hopital Haut Leveque Pessac Cedex France 33604
17 Local Institution - 401 Pessac Cedex France 33604
18 Institut Universitaire du Cancer de Toulouse (IUCT) - Oncopole Toulouse Cedex 9 France 31059
19 Local Institution - 404 Toulouse Cedex 9 France 31059
20 John Radcliffe Hospital Oxford United Kingdom OX3 9DU
21 Local Institution - 301 Oxford United Kingdom OX3 9DU

Sponsors and Collaborators

  • Celgene
  • AbbVie

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT04336982
Other Study ID Numbers:
  • CC-90009-AML-002
  • U1111-1247-5619
  • 2019-001681-15
First Posted:
Apr 7, 2020
Last Update Posted:
Jul 8, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Celgene
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 8, 2022