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

Arog Pharmaceuticals, Inc.28 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia

Interventions

Crenolanib besylateDRUG

IdarubicinDRUG

CytarabineDRUG

AzacytidineDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (1)

MD Anderson Cancer Center

Houston, Texas, United States

Outcomes

Primary Outcomes

Response Rate of Crenolanib Besylate Combination Therapy

To determine the response rate to crenolanib. CR Complete remission (CR) response criteria include a post-baseline bone marrow (BM) biopsy or aspiration % blasts \<5%, absolute neutrophil count (ANC) \>1×10\^9/L and platelet count \>100×10\^9/L. CRi response included all CR criteria met, except participant did not experience either platelet recovery or ANC recovery. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS. Death in aplasia response include deaths occurring following chemotherapy while cytopenic with an aplastic or hypoplastic BM prior to death without evidence of persistent leukemia.

Time frame: Baseline up to first documented response, persistent disease, or death (whichever occurs first), 1 year.

Data from ClinicalTrials.gov

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