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

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ClinicalTrials.gov Identifier: NCT02400255
Recruitment Status : Recruiting
First Posted : March 27, 2015
Last Update Posted : December 6, 2019
Sponsor:
Information provided by (Responsible Party):
Arog Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Crenolanib besylate Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Crenolanib Besylate Maintenance Following Allogeneic Stem Cell Transplantation in Patients With FLT3-positive Acute Myeloid Leukemia
Actual Study Start Date : September 2015
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021


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 45 days but no later than 90 days after allogeneic HSCT.
Drug: Crenolanib besylate
Other Name: 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 45 days but no later than 90 days after allogeneic HSCT.
Drug: Crenolanib besylate
Other Name: CP-868,596-26




Primary Outcome Measures :
  1. progression-free survival (PFS) [ Time Frame: 2 years ]
    PFS, defined as the time to disease progression or death, whichever occurs first, starting when crenolanib administration is begun.


Secondary Outcome Measures :
  1. disease-free survival (DFS) [ Time Frame: 2 years ]
  2. overall survival (OS) [ Time Frame: 2 years ]
  3. graft-versus-host disease [ Time Frame: 2 years ]
  4. 100-day transplant-related mortality [ Time Frame: 4 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02400255


Contacts
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Contact: Vinoo Urity 214-593-0521 vurity@arogpharma.com

Locations
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United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Richard Champlin, M.D.    713-792-3618    rchampli@mdanderson.org   
Contact: Betul Oran, M.D.    713-745-2820    boran@mdanderson.org   
Sponsors and Collaborators
Arog Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Richard Champlin, MD M.D. Anderson Cancer Center

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Responsible Party: Arog Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02400255     History of Changes
Other Study ID Numbers: ARO-009
First Posted: March 27, 2015    Key Record Dates
Last Update Posted: December 6, 2019
Last Verified: December 2019
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Crenolanib
Antineoplastic Agents