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

Acute Myeloid Leukemia Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02400281
• Other study ID #: ARO-010
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2015
• Est. completion date: July 15, 2020

Study information

• Verified date: February 2024
• Source: Arog Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: July 15, 2020
• Est. primary completion date: July 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Drug:
• Crenolanib besylate

• Idarubicin

• Cytarabine

• Azacytidine

• Mitoxantrone

• Etoposide

• Fludarabine

• G-CSF

Locations

Country	Name	City	State
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Arog Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline up to first documented response, persistent disease, or death (whichever occurs first), 1 year.