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

February 21, 2024 updated by: Arog Pharmaceuticals, Inc.

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1 crenolanib besylate combination
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
Drug: Fludarabine
Other Names:
  • Fludarabine phosphate
Drug: Mitoxantrone
Other Names:
  • Novantrone
Drug: Cytarabine
Other Names:
  • cytosine arabinoside
Drug: G-CSF
Drug: Etoposide
Other Names:
  • etoposide phosphate
Drug: Idarubicin
Other Names:
  • 4-demethoxydaunorubicin
Drug: Crenolanib besylate
Other Names:
  • CP-868,596-26
Experimental: Arm 2 crenolanib besylate combination
Arm 2 patients will receive crenolanib besylate and azacytidine.
Drug: Azacytidine
Other Names:
  • 5-azacytidine
Drug: Crenolanib besylate
Other Names:
  • CP-868,596-26

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate of Crenolanib Besylate Combination Therapy
Time Frame: Baseline up to first documented response, persistent disease, or death (whichever occurs first), 1 year.
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.

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 2 years
2 years
Progression free survival
Time Frame: 2 years
2 years
Duration of response
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Arog Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Jorge Cortes, MD, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Actual)

July 15, 2020

Study Completion (Actual)

July 15, 2020

Study Registration Dates

First Submitted

March 18, 2015

First Submitted That Met QC Criteria

March 23, 2015

First Posted (Estimated)

March 27, 2015

Study Record Updates

Last Update Posted (Actual)

March 20, 2024

Last Update Submitted That Met QC Criteria

February 21, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARO-010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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