Clinical Trials /

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

NCT02400255

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ARO-009
  • NCT ID: NCT02400255

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Crenolanib besylateCP-868,596-26Cohort A

Purpose

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.

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 30
      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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort AExperimentalCohort 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 45 days but no later than 90 days after allogeneic HSCT.
  • Crenolanib besylate
Cohort BExperimentalCohort 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 45 days but no later than 90 days after allogeneic HSCT.
  • Crenolanib besylate

Eligibility Criteria

        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 45 days but no later than 90 days after allogeneic HSCT.

          8. Post-transplant bone marrow blast count ≤ 5% confirmed by standard of care bone marrow
             biopsy performed post-transplant (at least 30 days post-transplant).

          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 109/L
             without daily use of myeloid growth factor; and platelet ≥ 25 x 109/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. Active GVHD grade ≥ 2

          2. Concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg

          3. Active and/or untreated central nervous system (CNS) leukemia

          4. Concomitant therapies for treatment or control of leukemia.

          5. 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

          6. Uncontrolled infection

          7. Known positive for human immunodeficiency virus (HIV); active hepatitis B (HBV) or
             hepatitis C (HCV) infection

          8. Significant cardiac disease (New York Heart Association classes III or IV) or unstable
             angina despite medication

          9. Pregnant or breast-feeding

         10. Receipt of investigational agents within 5 half-lives of last dose of investigational
             agent

         11. Prior treatment with crenolanib with progression on treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:PFS, defined as the time to disease progression or death, whichever occurs first, starting when crenolanib administration is begun.

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arog Pharmaceuticals, Inc.

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