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

Arog Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Idarubicin; Drug: Crenolanib besylate; Drug: Mitoxantrone; Drug: Fludarabine; Drug: Cytarabine; Drug: Azacytidine; Drug: G-CSF; Drug: Etoposide

Study type: Interventional

Funder types: Industry

Identifiers

NCT02400281

ARO-010

Details and patient eligibility

About

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

Full 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.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Arm 1 crenolanib besylate combination

Experimental group

Description:

Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin

Treatment:

Drug: G-CSF

Drug: Etoposide

Drug: Cytarabine

Drug: Fludarabine

Drug: Mitoxantrone

Drug: Crenolanib besylate

Drug: Idarubicin

Arm 2 crenolanib besylate combination

Experimental group

Description:

Arm 2 patients will receive crenolanib besylate and azacytidine.

Treatment:

Drug: Azacytidine

Drug: Crenolanib besylate