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

Leukemia, Myeloid, Acute Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04336982
• Other study ID #: CC-90009-AML-002
• Secondary ID: U1111-1247-56192
• Status: Terminated
• Phase: Phase 1
• Start date: August 5, 2020
• Est. completion date: April 5, 2024

Study information

• Verified date: May 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: April 5, 2024
• Est. primary completion date: October 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

2. Part A: Primary Refractory AML, or AML in first relapse, and is = 18 years of age

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

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

1. Subject is = 18 years of age.

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

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/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 = 30 mL/min.

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• CC-90009
Injection
• Venetoclax
Tablet
• Azacitidine
Injection
• Gilteritinib
Tablet

Locations

Country	Name	City	State
Belgium	Local Institution - UNK3	Yvoir
Canada	Local Institution - 202	Edmonton	Alberta
Canada	Local Institution - 201	Toronto	Ontario
France	Local Institution - 402	Marseille
France	Local Institution - 401	Pessac Cedex
France	Local Institution - 404	Toulouse Cedex 9
United Kingdom	Local Institution - 301	Oxford
United States	Local Institution - 103	Boston	Massachusetts
United States	Local Institution - 108	Hackensack	New Jersey
United States	Local Institution - 105	Houston	Texas
United States	Local Institution - 107	New Haven	Connecticut
United States	Local Institution - 101	Saint Louis	Missouri
United States	Local Institution - 104	San Francisco	California
United States	Local Institution - 102	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Celgene	AbbVie

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity (DLT)	Number of participants with a DLT	Up to 28 days
Primary	Adverse Events (AEs)	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.	Up to 28 days after last dose of study drug.
Secondary	Complete Remission Rate (CRR),	is defined as the rate for any type of CR or CRh	Up to 3 years
Secondary	Objective Response Rate (ORR)	includes all responses of complete remissions (CRs), Morphologic leukemia-free state (MLFS), and Partial remission (PR)	Up to 3 years
Secondary	Progression Free Survival (PFS)	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	Up to 3 years
Secondary	Overall Survival (OS)	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.	Up to 3 years
Secondary	Duration of Remission	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.	Up to 3 years
Secondary	Time to Remission	is measured from the time when criteria for CR/CRh/PR are first met (whichever is first recorded)	Up to 3 years
Secondary	Pharmacokinetics - Cmax	observed maximum concentration in plasma	Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)
Secondary	Pharmacokinetics - AUC24	area under the plasma concentration time-curve from time 0 to 24 hours postdose	Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)
Secondary	Pharmacokinetics - t1/2	terminal half life	Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting