A Safety and Efficacy Study of CC-90009 Combinations in Subjects With Acute Myeloid Leukemia
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
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
- Dose Limiting Toxicity (DLT) [Up to 28 days]
Number of participants with a DLT
- 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
- Complete Remission Rate (CRR), [Up to 3 years]
is defined as the rate for any type of CR or CRh
- Objective Response Rate (ORR) [Up to 3 years]
includes all responses of complete remissions (CRs), Morphologic leukemia-free state (MLFS), and Partial remission (PR)
- 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
- 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.
- 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.
- 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)
- 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
- 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
- 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
Inclusion Criteria:
-
Adult subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
-
Arm A (CC-90009 + venetoclax/azacitidine):
-
Part A: Newly diagnosed AML with poor/adverse risk genetic abnormalities and is ≥ 75 years of age or intensive chemotherapy ineligible OR
-
Part A: Refractory AML and is ≥ 18 years of age
-
Part B: Newly diagnosed AML and is ≥ 75 years of age or intensive chemotherapy ineligible
-
Arm B (CC-90009 + gilteritinib):
-
Subject is ≥ 18 years of age.
-
Fms-like tyrosine kinase 3 (FLT3) mutation positive.
-
Gilteritinib treatment naïve
-
Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
-
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.
- Agree to follow the CC-90009 Pregnancy Prevention Plan (PPP) and combination agents' requirements.
Exclusion Criteria:
-
Subject with acute promyelocytic leukemia (APL)
-
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
-
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)
-
Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing
-
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
-
Subject has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2
-
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.
-
Disorders or conditions disrupting normal calcium homeostasis or preventing calcium supplementation.
-
Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
-
Left ventricular ejection fraction (LVEF) < 45% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
-
Complete left bundle branch or bifascicular block.
-
Congenital long QT syndrome.
-
Persistent or clinically meaningful ventricular arrhythmias.
-
QTcF ≥ 470 ms (Arm A) or > 450 ms (Arm B) on Screening electrocardiogram (ECG)
-
Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting study treatments or unstable arrhythmia.
-
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.
-
Subject is a pregnant or lactating female
-
Additional exclusion criteria based on combination agent:
- 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.
- Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.
- 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.
- 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.- CC-90009-AML-002
- U1111-1247-5619
- 2019-001681-15