Clinical Trials /

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

NCT04336982

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).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
CC-90009CC-90009 in combination with venetoclax and azacitidine
VenetoclaxCC-90009 in combination with venetoclax and azacitidine
AzacitidineCC-90009 in combination with venetoclax and azacitidine
GilteritinibCC-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

NameTypeDescriptionInterventions
CC-90009 in combination with venetoclax and azacitidineExperimentalCC-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 gilteritinibExperimentalCC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Gilteritinib will be administered orally QD.
  • Gilteritinib

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

          8. 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.

             suspected during screening.

          9. Subject is a pregnant or lactating female

         10. 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.
      
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:Not yet recruiting
Lead Sponsor:Celgene

Trial Keywords

  • CC-90009
  • Venetoclax
  • Azacitidine
  • Gilteritinib
  • Hematologic cancers
  • Leukemia
  • Acute myeloid leukemia
  • AML

Last Updated

April 27, 2020