Description:
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 subjects with acute
myeloid leukemia (AML).
Title
- Brief Title: A Safety and Efficacy Study of CC-90009 Combinations in Subjects With Acute Myeloid Leukemia
- Official Title: An Exploratory Phase 1/2 Open-Label Multi-Arm Trial to Evaluate the Safety and Efficacy of CC-90009 Combinations in Subjects With Acute Myeloid Leukemia
Clinical Trial IDs
- ORG STUDY ID:
CC-90009-AML-002
- SECONDARY ID:
U1111-1247-5619
- SECONDARY ID:
2019-001681-15
- NCT ID:
NCT04336982
Conditions
Interventions
Drug | Synonyms | Arms |
---|
CC-90009 | | CC-90009 in combination with venetoclax and azacitidine |
Venetoclax | | CC-90009 in combination with venetoclax and azacitidine |
Azacitidine | | CC-90009 in combination with venetoclax and azacitidine |
Gilteritinib | | CC-90009 in combination with gilteritinib |
Purpose
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 subjects with acute
myeloid leukemia (AML).
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.
Trial Arms
Name | Type | Description | Interventions |
---|
CC-90009 in combination with venetoclax and azacitidine | Experimental | 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. | - CC-90009
- Venetoclax
- Azacitidine
|
CC-90009 in combination with gilteritinib | Experimental | CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Gilteritinib will be administered orally QD. | |
Eligibility Criteria
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):
1. Newly diagnosed AML and is ≥ 75 years of age or intensive chemotherapy ineligible
OR
2. Refractory AML and is ≥ 18 years of age
3. Arm B (CC-90009 + gilteritinib):
1. Subject is ≥ 18 years of age.
2. FLT3-ITD positive relapsed or refractory AML.
3. Gilteritinib treatment naïve
4. Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
5. Subject must have the following screening laboratory values:
- Total White Blood Cell count (WBC) < 25 x 10^9 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.
6. 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:
1. Left ventricular ejection fraction (LVEF) < 45% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO).
2. Complete left bundle branch or bifascicular block.
3. Congenital long QT syndrome.
4. Persistent or clinically meaningful ventricular arrhythmias.
5. QTcF ≥ 470 ms (Arm A) or > 450 ms (Arm B) on Screening electrocardiogram (ECG)
6. Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting
study treatments or unstable arrhythmia.
7. 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.
10. Subject is a pregnant or lactating female
11. Additional exclusion criteria based on combination agent:
a. 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.
12. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20
days for severe/critical illness prior to C1D1.
a. 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.
13. Previous SARS-CoV-2 vaccine within 14 days of C1D1.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose Limiting Toxicity (DLT) |
Time Frame: | Up to 28 days |
Safety Issue: | |
Description: | Number of participants with a DLT |
Secondary Outcome Measures
Measure: | Complete Remission Rate (CRR), |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | is defined as the rate for any type of CR or CRh |
Measure: | Objective Response Rate (ORR) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | is defined as the rate for all types of CRs and PR for AML. |
Measure: | Progression Free Survival (PFS) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | 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 |
Measure: | Overall Survival (OS) |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | 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. |
Measure: | Duration of Remission |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | 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. |
Measure: | Time to Remission |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | is measured from the time when criteria for CR/CRh/PR are first met (whichever is first recorded) |
Measure: | Pharmacokinetics - Cmax |
Time Frame: | Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3) |
Safety Issue: | |
Description: | observed maximum concentration in plasma |
Measure: | Pharmacokinetics - AUC24 |
Time Frame: | Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3) |
Safety Issue: | |
Description: | area under the plasma concentration time-curve from time 0 to 24 hours postdose |
Measure: | Pharmacokinetics - t1/2 |
Time Frame: | Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3) |
Safety Issue: | |
Description: | terminal half life |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Celgene |
Trial Keywords
- CC-90009
- Venetoclax
- Azacitidine
- Gilteritinib
- Hematologic cancers
- Leukemia
- Acute myeloid leukemia
- AML
Last Updated
August 20, 2021