Crenolanib Maintenance Following Allogeneic Stem Cell Transplantation in FLT3-positive Acute Myeloid Leukemia Patients

NCT02400255 | Completed Phase 2 Results

• 1 other identifier: ARO-009
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, Phase II study of crenolanib as maintenance in AML patients with FLT3 mutations who have achieved complete remission (CR) after allogeneic stem cell transplantation. Oral crenolanib will be administered daily post-transplant for up to two years.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Relapsed

  Patients who relapsed during or after crenolanib maintenance therapy were categorized as those who received \<28 days of maintenance and those who received \>28 days of maintenance.

  2 years

Study Arms (2)

Cohort A

EXPERIMENTAL

Cohort A will include patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) while in first or second complete remission with count recovery. Crenolanib besylate maintenance therapy will start at the earliest time no sooner than 42 days but no later than 90 days after allogeneic HSCT.

Drug: Crenolanib besylate

Cohort B

EXPERIMENTAL

Cohort B will include patients who underwent HSCT with incomplete count recovery although they had ≤%10 bone marrow blasts at the time of HSCT. Crenolanib besylate maintenance therapy will start at the earliest time no sooner than 42 days but no later than 90 days after allogeneic HSCT.

Drug: Crenolanib besylate

Interventions

Crenolanib besylate DRUG

Also known as: CP-868,596-26

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of AML according to World Health Organization (WHO) classification
• First allogeneic hematopoietic stem cell transplantation (HSCT) using myeloablative conditioning (MAC), non-myeloablative (NMA), or reduced-intensity conditioning (RIC) preparative regimens.
• FLT3-ITD or FLT3-D835 positive disease at any time during disease course.
• Hematopoietic stem cell source is either with peripheral blood, bone marrow or cord blood.
• Donor source is matched related, unrelated, haploidentical donor or cord blood.
• At the time of allogeneic HSCT:
• No more than 1 antigen mismatch at HLA-A, -B, -C, -DRB1 or -DQB1 locus for unrelated donor with peripheral blood and bone marrow as the hematopoietic stem cell source; and
• Bone marrow blast ≤ 10%
• No sooner than 42 days but no later than 90 days after allogeneic HSCT.
• Post-transplant bone marrow blast count ≤ 5% confirmed within 21 days (+4 days) prior to starting study therapy
• Evidence of donor engraftment as defined by institutional standard T cell chimerism \> 50%.
• Adequate engraftment within 7 days prior to starting study therapy: ANC ≥ 1.0 x 10\^9/L without daily use of myeloid growth factor; and platelet ≥ 25 x 10\^9/L without platelet transfusion within 1 week
• Non-hematological toxicities ≤ Grade 2
• Serum creatinine ≤ 1.5 × ULN OR creatinine clearance ≥ 50mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
• Adequate liver function with serum AST, ALT and bilirubin within the normal range at the time of crenolanib commencement

You may not qualify if:

• Bone marrow blast \>5% within 21 days (+4 days) of start of study drug
• Active GVHD grade ≥ 2
• Concurrent use of corticosteroids equivalent of prednisone at a dose \> 0.5 mg/kg
• Active and/or untreated central nervous system (CNS) leukemia
• Concomitant therapies for treatment or control of leukemia.
• Use of any of the following after transplantation and prior to starting study therapy:
• Chemotherapeutic agents for therapy of AML (note that prophylactic use of these agents is allowed in this study, e.g., methotrexate for GVHD)
• Investigational agents/therapies
• Azacitidine, decitabine or other demethylating agents
• Lenalidomide, thalidomide and pomalidomide
• Uncontrolled infection
• Known positive for human immunodeficiency virus (HIV); active hepatitis B (HBV) or hepatitis C (HCV) infection
• Significant cardiac disease (New York Heart Association classes III or IV) or unstable angina despite medication
• Pregnant or breast-feeding
• Major surgery within 4 weeks of starting study drug

Sponsors & Collaborators

• Arog Pharmaceuticals, Inc.: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Edward McDonald
• Organization: Arog Pharmaceuticals

emcdonald@arogpharma.com

214-593-0500

Study Officials

• Richard Champlin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2015
• First Posted: March 27, 2015
• Study Start: September 1, 2015
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: December 18, 2023
• Results First Posted: December 18, 2023

Record last verified: 2023-12

Locations

US (1)