Clinical Trials /

Study of Crenolanib Combined With Chemotherapy in FLT3-mutated Acute Myeloid Leukemia Patients

NCT02400281

Description:

This is an open label, two-arm, Phase I-II trial, non-randomized. Arm 1: crenolanib with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin) Arm 2: crenolanib with 5-azacitidine

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Crenolanib Combined With Chemotherapy in FLT3-mutated Acute Myeloid Leukemia Patients
  • Official Title: Phase I-II Study of Crenolanib Combined With Standard Salvage Chemotherapy, and Crenolanib Combined With 5-Azacitidine in Acute Myeloid Leukemia Patients With FLT3 Activating Mutations

Clinical Trial IDs

  • ORG STUDY ID: ARO-010
  • NCT ID: NCT02400281

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Crenolanib besylateCP-868,596-26Arm 1 crenolanib besylate combination
Idarubicin4-demethoxydaunorubicinArm 1 crenolanib besylate combination
Cytarabinecytosine arabinosideArm 1 crenolanib besylate combination
Azacytidine5-azacytidineArm 2 crenolanib besylate combination
MitoxantroneNovantroneArm 1 crenolanib besylate combination
Etoposideetoposide phosphateArm 1 crenolanib besylate combination
FludarabineFludarabine phosphateArm 1 crenolanib besylate combination
G-CSFArm 1 crenolanib besylate combination

Purpose

This is an open label, two-arm, Phase I-II trial, non-randomized. Arm 1: crenolanib with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin) Arm 2: crenolanib with 5-azacitidine

Detailed Description

      For each arm:

      The phase I with dose-limiting toxicity (DLT) determination will use 3+3 design.

      Phase II total of 52 patients (26 per arm) will be treated at established phase I dose.

      Enrollment to be simultaneous to each arm.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1 crenolanib besylate combinationExperimentalArm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
  • Crenolanib besylate
  • Idarubicin
  • Cytarabine
  • Mitoxantrone
  • Etoposide
  • Fludarabine
  • G-CSF
Arm 2 crenolanib besylate combinationExperimentalArm 2 patients will receive crenolanib besylate and azacytidine.
  • Crenolanib besylate
  • Azacytidine

Eligibility Criteria

        Inclusion Criteria:

          1. Confirmed diagnosis of refractory/relapsed AML or high-risk MDS

               -  Arm 1: Subjects must have received at least one prior therapy and a maximum of
                  three prior therapies

               -  Arm 2: Subjects must have received at least one prior therapy and a maximum of
                  three prior therapies. No prior treatment with 5-Azacitidine is allowed in this
                  arm.

          2. FLT3 mutation positive (ITD, TKD or other)

          3. ECOG PS 0-2

          4. Adequate liver and renal function

          5. Negative pregnancy test

          6. Extramedullary leukemia allowed except CNS disease

        Exclusion Criteria:

          -  Arm 1 and 2 Exclusion:

               1. <5% blasts in marrow or blood at time of screening

               2. Active HIV, hepatitis B or C

               3. CNS leukemia

               4. Clinically significant GVHD or organ dysfunction where chemotherapy specified by
                  protocol cannot be given

               5. Patient with AML-M3 (APL)

               6. Pre-existing liver diseases (i.e. cirrhosis, chronic hepatitis B or C,
                  nonalcoholic steatohepatitis, sclerosing cholangitis)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicities of crenolanib besylate combination therapy
Time Frame:6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of response
Time Frame:2 years
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Arog Pharmaceuticals, Inc.

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