Phase II Study of Crenolanib in Subjects With Relapsed/Refractory AML With FLT3 Activating Mutations

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Arog Pharmaceuticals LLC
ClinicalTrials.gov Identifier:
NCT01522469
First received: January 30, 2012
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed or refractory AML with FLT3 activating mutations. Prior treatment with other FLT3 TKIs is allowed. Subjects will take crenolanib 200mg/m2/day divided in three doses daily (preferably every eight hours), taken orally at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who are able to proceed to allogeneic stem cell transplant will be able to resume crenolanib therapy post-transplant in an attempt to maintain remission.


Condition Intervention Phase
Relapsed or Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations
Drug: Crenolanib Besylate (CP-868,596-26)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Crenolanib Besylate in Subjects With Relapsed/Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations

Resource links provided by NLM:


Further study details as provided by Arog Pharmaceuticals LLC:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the overall response rate defined as Complete remission (CR) including incomplete blood count recovery (CRi)

  • Duration of response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the length of time patients experience a clinical response in their disease while receiving crenolanib therapy

  • Duration of progression-free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    For patients who receive crenolanib therapy, to determine the length of time that passes between the start of therapy and progression of disease


Secondary Outcome Measures:
  • Impact of crenolanib on patient experience [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The impact of crenolanib on patient experience will be determined by measuring patient hematological improvement, bridge to transplant, duration of leukemia control, blood and platelet transfusions, infections, days of hospitalization, and performance status

  • Safety of crenolanib [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    The safety and tolerability of crenolanib will be determined by assessing the adverse events experienced by patients

  • Pharmacokinetic analysis of crenolanib in patients with AML [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The bioavailability of crenolanib will be assessed by performing pharmacokinetic analysis of patients' serum samples

  • Analysis of pharmacodynamic markers [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Analysis of phospho-FLT3 and other pharmacodynamic markers from serially collected circulating leukemic blasts and/or marrow blast samples

  • Analysis of Pharmacogenetics [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Pharmacogenetic analyses, correlation of remission with genomic abnormalities including but not limited to mutant FLT3 allelic ratio


Enrollment: 20
Study Start Date: July 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Crenolanib Besylate Drug: Crenolanib Besylate (CP-868,596-26)
Subjects will take crenolanib 200mg/m2/day divided in three doses daily (preferably every eight hours), taken orally at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who are able to proceed to allogeneic stem cell transplant will be able to resume crenolanib therapy post-transplant in an attempt to maintain remission.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed/refractory primary AML or AML secondary to antecedent hematologic disorder with an expected survival of 3 months or greater
  • Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within < 60 days of the screening period.
  • Age ≥18 years
  • ECOG PS 0 - 2
  • Adequate liver function, defined as total or direct bilirubin ≤1.5x ULN, ALT ≤3.0x ULN,AST ≤3.0x ULN. Exceptions for ALT and AST restrictions will be made in the setting of documented liver involvement with leukemia
  • Adequate renal function, defined as serum creatinine ≤1.5x ULN
  • Recovery from non-hematological toxicities of prior therapy (including HSCT) to no more than grade 1 (except alopecia)
  • Subjects should have received no anti-leukemic therapy (except hydroxyurea) prior to the first dose of crenolanib as follows: for 14 days for classical cytotoxic agents and for five times the t1/2 (half-life) for FLT3 inhibitors and antineoplastic agents that are neither cytotoxic nor FLT3 inhibitors (e.g. hypomethylating agent or MEK inhibitor)
  • Negative pregnancy test for women of childbearing potential
  • Able and willing to provide written informed consent
  • Subjects who received crenolanib prior to and are within 30-90 days of an allogeneic stem cell transplant (HSCT) and have either no active GVHD where therapy has been initiated or GVHD where therapy has not been escalated within 14 days prior to start of study drug

Exclusion Criteria:

  • Absence of FLT3 activating mutation
  • <5% blasts in blood or marrow at screening
  • Concurrent chemotherapy, systemic immunosuppressants, or targeted anti-cancer agents,other than hydroxyurea
  • Patient with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
  • HIV infection or active hepatitis B manifested as hepatitis surface antigen positive (HepBsAg) or hepatitis C manifested as hepatitis C antibody positive
  • For post HSCT, subjects who are within 29 days of an allogeneic transplant, and/or are on an unstable dose of immunosuppressive drugs for management or prophylaxis of GVHD or have escalated therapy for GVHD within 14 days of starting study drug and/or have >/=Grade 2 persistent non hematological toxicity related to the transplant or did not receive crenolanib prior to HSCT
  • Evidence of lack of engraftment if post allogeneic transplant
  • Unable to swallow pills
  • Major surgical procedures within 14 days of Cycle 1 Day 1 administration of crenolanib
  • Unwillingness or inability to comply with protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01522469

Locations
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Arog Pharmaceuticals LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Arog Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT01522469     History of Changes
Other Study ID Numbers: ARO-004
Study First Received: January 30, 2012
Last Updated: February 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Arog Pharmaceuticals LLC:
FLT3
Crenolanib
Acute
myeloid
leukemia
relapsed
refractory

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Crenolanib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014