Crenolanib Maintenance Following Allogeneic Stem Cell Transplantation in FLT3-positive Acute Myeloid Leukemia Patients
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Crenolanib besylate
Intervention MeSH terms: Crenolanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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 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