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

A Phase II Study of Crenolanib Besylate Maintenance Following Allogeneic Stem Cell Transplantation in Patients With FLT3-positive Acute Myeloid Leukemia

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Crenolanib besylate

Detailed Description

There are two patient subgroups: 1) those who were in complete remission (CR) at the time of transplant, and 2) those who were not in complete remission (NCR) at the time of transplant. Start of crenolanib therapy at 100 mg TID is intended at the earliest time no sooner than 42 days but no later than 90 days after allogeneic stem cell transplantation. Patients may take crenolanib continuously for up to 728 days or until one of the criteria for study discontinuation is fulfilled.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. History of AML according to World Health Organization (WHO) classification
2. First allogeneic hematopoietic stem cell transplantation (HSCT) using myeloablative conditioning (MAC), non-myeloablative (NMA), or reduced-intensity conditioning (RIC) preparative regimens.
3. FLT3-ITD or FLT3-D835 positive disease at any time during disease course.
4. Hematopoietic stem cell source is either with peripheral blood, bone marrow or cord blood.
5. Donor source is matched related, unrelated, haploidentical donor or cord blood.

6. At the time of allogeneic HSCT:

   1. 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
   2. Bone marrow blast ≤ 10%
7. No sooner than 42 days but no later than 90 days after allogeneic HSCT.
8. Post-transplant bone marrow blast count ≤ 5% confirmed within 21 days (+4 days) prior to starting study therapy
9. Evidence of donor engraftment as defined by institutional standard T cell chimerism > 50%.
10. 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
11. Non-hematological toxicities ≤ Grade 2
12. Serum creatinine ≤ 1.5 × ULN OR creatinine clearance ≥ 50mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
13. Adequate liver function with serum AST, ALT and bilirubin within the normal range at the time of crenolanib commencement
14. Acute graft-versus-host disease (GVHD) ≤ Grade 1, either no signs of chronic GVHD or mild chronic GVHD graded as limited disease
15. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
16. Age ≥ 18 years with the capacity to give written informed consent
17. Non-pregnant and non-nursing women of childbearing potential must have a negative serum or urine pregnancy test ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months)
18. Women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for 90 days following completion of therapy

Exclusion Criteria:

1. Bone marrow blast >5% within 21 days (+4 days) of start of study drug
2. Active GVHD grade ≥ 2
3. Concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg
4. Active and/or untreated central nervous system (CNS) leukemia
5. Concomitant therapies for treatment or control of leukemia.

6. Use of any of the following after transplantation and prior to starting study therapy:

   1. Chemotherapeutic agents for therapy of AML (note that prophylactic use of these agents is allowed in this study, e.g., methotrexate for GVHD)
   2. Investigational agents/therapies
   3. Azacitidine, decitabine or other demethylating agents
   4. Lenalidomide, thalidomide and pomalidomide
7. Uncontrolled infection
8. Known positive for human immunodeficiency virus (HIV); active hepatitis B (HBV) or hepatitis C (HCV) infection
9. Significant cardiac disease (New York Heart Association classes III or IV) or unstable angina despite medication
10. Pregnant or breast-feeding
11. Major surgery within 4 weeks of starting study drug
12. Receipt of investigational agents within 5 half-lives of last dose of investigational agent
13. Prior treatment with crenolanib with progression on treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; 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; Other Names: CP-868,596-26
Experimental: Cohort B; 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; Other Names: CP-868,596-26

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival (OS)	2 years
disease-free survival (DFS)	2 years
graft-versus-host disease	2 years
100-day transplant-related mortality	4 months

Collaborators and Investigators

• Sponsor: Arog Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Richard Champlin, MD, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): May 1, 2022

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 (Estimated): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Crenolanib
• Other Study ID Numbers: ARO-009