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Trial record 12 of 19 for:    arog

A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients With FLT3 Activating Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01657682
Recruitment Status : Completed
First Posted : August 6, 2012
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
Arog Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE July 31, 2012
First Posted Date  ICMJE August 6, 2012
Last Update Posted Date July 2, 2019
Study Start Date  ICMJE October 2012
Actual Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 31, 2013)
  • Response rate of patients receiving crenolanib therapy [ Time Frame: 1 year ]
    To determine the response rate to crenolanib, including the rates of complete remission (CR), CR with incomplete blood count recovery (CRi), and partial remission (PR), in relapsed/refractory AML patients with FLT3 activating mutations after first cycle (28-days) and at best response.
  • Toxicity rate associated with crenolanib therapy [ Time Frame: 1 year ]
    To determine the safety and tolerability of crenolanib in AML patients with FLT3 activating mutations. The two cohorts of patients will be jointly monitored for the safety. The toxicity is defined as any grade 4 or greater non-hematologic toxicities attributed to the study drug. Targeting a 30% toxicity rate as a trade-off, the trial will be stopped early according to the following monitoring rule. If at any time during the study we determine that there is more than a 95% chance that the toxicity rate is more than 30% we will stop the study. Crenolanib has been well tolerated in studies including over 100 patients and toxicity patterns are relatively well understood.
Original Primary Outcome Measures  ICMJE
 (submitted: August 1, 2012)
  • Response rate of patients receiving crenolanib therapy [ Time Frame: 1 year ]
    To determine the response rate to crenolanib, including the rates of complete remission (CR), CR with incomplete blood count recovery (CRi), and partial remission (PR), in relapsed/refractory AML patients with FLT3 activating mutations after first cycle (28-days).
  • Toxicity rate associated with crenolanib therapy [ Time Frame: 1 year ]
    To determine the safety and tolerability of crenolanib in AML patients with FLT3 activating mutations. The two cohorts of patients will be jointly monitored for the safety. The toxicity is defined as any grade 4 or greater non-hematologic toxicities attributed to the study drug. Targeting a 30% toxicity rate as a trade-off, the trial will be stopped early according to the following monitoring rule. If at any time during the study we determine that there is more than a 95% chance that the toxicity rate is more than 30% we will stop the study. Crenolanib has been well tolerated in studies including over 100 patients and toxicity patterns are relatively well understood.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
  • Duration of response [ Time Frame: 1 year ]
    To determine the duration of clinical response in AML patients with FLT3 activating mutations treated with crenolanib.
  • Pharmacodynamic markers [ Time Frame: 1 year ]
    To analyze phospho-FLT3 and other pharmacodynamic markers from serially collected circulating leukemic blasts and/or marrow blast samples
  • Duration of progression-free survival and overall survival [ Time Frame: 1 year ]
    To determine the progression free survival and overall survival of AML patients with activating FLT3 mutations treated with crenolanib
  • Pharmacokinetic markers [ Time Frame: 1 year ]
    To characterize the pharmacokinetics of crenolanib in adult patients and relate drug disposition to outcome or pharmacodynamic markers (i.e. toxicity and/or FLT3 inhibition)
Original Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2012)
  • Duration of response [ Time Frame: 1 year ]
    To determine the duration of clinical response in AML patients with FLT3 activating mutations treated with crenolanib.
  • Pharmacodynamic markers [ Time Frame: 1 year ]
    To analyze phospho-FLT3 and other pharmacodynamic markers from serially collected circulating leukemic blasts and/or marrow blast samples
  • Duration of progression-free survival [ Time Frame: 1 year ]
    To determine the length of time that passes between start of crenolanib therapy and progression of disease in patients who receive crenolanib therapy
  • Pharmacokinetic markers [ Time Frame: 1 year ]
    To characterize the pharmacokinetics of crenolanib in adult patients and relate drug disposition to outcome or pharmacodynamic markers (i.e. toxicity and/or FLT3 inhibition)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients With FLT3 Activating Mutations
Official Title  ICMJE A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients With FLT3 Activating Mutations
Brief Summary This pilot Phase II study is designed to evaluate the efficacy and tolerability of crenolanib in two cohorts of AML patients with FLT3 activation mutations (patients whose leukemia has recurred after prior chemotherapy not including a FLT3 TKI and patients whose leukemia has progressed after prior therapy with a FLT3 TKI).
Detailed Description This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed acute myeloid leukemia (AML) with FLT3 activating mutations. Two cohorts of patients will be enrolled: those whose AML has recurred after prior chemotherapy without a FLT3 TKI, and those whose AML has progressed after prior therapy with FLT3 TKIs. Subjects will take Crenolanib besylate at 100 mg TID until disease progression, death, or unacceptable toxicities. Concurrent hydroxyurea is permitted during the first 28 days of study therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia With FLT3 Activating Mutations That Has Relapsed or Been Refractory After One or More Prior Therapies
Intervention  ICMJE Drug: Crenolanib besylate

Crenolanib besylate, 100 mg TID, taken orally at least 30 minutes pre- or post- meal. Patients will complete a daily diary to record the date, time and amount (number of tablets) of crenolanib taken and eating schedule.

Concurrent hydroxyurea (maximum 5g total daily dose x 14 days) is permitted during the first 28 days of study therapy.

Study Arms  ICMJE
  • Experimental: Cohort A - No prior FLT3 TKI exposure
    Will enroll relapsed/refractory AML patients with FLT3 activating mutations who progressed on one or more prior chemotherapy regimens excluding any FLT3 TKI.
    Intervention: Drug: Crenolanib besylate
  • Experimental: Cohort B - Prior therapy with FLT3 TKI
    Will enroll relapsed/refractory AML patients with FLT3 activating mutations whose leukemia has progressed and have history of prior therapy with one or more FLT3 TKIs.
    Intervention: Drug: Crenolanib besylate
Publications * Galanis A, Ma H, Rajkhowa T, Ramachandran A, Small D, Cortes J, Levis M. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood. 2014 Jan 2;123(1):94-100. doi: 10.1182/blood-2013-10-529313. Epub 2013 Nov 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: December 23, 2014)
70
Original Estimated Enrollment  ICMJE
 (submitted: August 1, 2012)
41
Actual Study Completion Date  ICMJE April 2019
Actual Primary Completion Date April 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Confirmed primary AML relapsed or refractory after prior therapy, AML secondary to antecedent chemotherapy or radiation therapy, or AML due to prior myelodysplastic syndrome (MDS)/ myeloproliferative neoplasm (MPN) as defined by WHO criteria with presence of either FLT3 ITD and/or other FLT3 activating mutations
  • Patients with secondary AML should have failed no more than two (2) prior regimens
  • Patients with antecedent MDS/MPN, defined by WHO criteria, without any prior therapy for AML, regardless of the number of therapies for MDS/ MPN
  • Patients with primary AML should have received no more than two (2) prior cytotoxic containing salvage regimens. Reinduction with the same regimen or stem cell transplant will not be considered a separate salvage regimen. Change of drugs will be considered a salvage regimen. Unlimited FLT3 TKI therapy (even in combination with cytotoxics/hypomethylating agents) is allowed for patients enrolled in cohort B
  • Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within 30 day screening period
  • Males and females age ≥18 years
  • ECOG PS 0-2
  • Adequate liver function, defined as bilirubin ≤1.5x ULN, ALT ≤3.0x ULN, and AST ≤3.0x ULN
  • 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 WOCBP
  • Able and willing to provide written informed consent.

Exclusion Criteria:

  • Absence of a FLT3 activating mutation
  • <5% blasts in blood or marrow at screening
  • Concurrent chemotherapy, 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 (defined as hepatitis B surface antigen positive) or C (defined as hepatitis C antibody positive)
  • Known clinically active central nervous system (CNS) leukemia
  • Patients less than 30 days post HSCT
  • Subjects who have clinically significant graft versus host disease requiring treatment and /or have >grade 2 persistent non hematological toxicity related to transplant
  • Prior crenolanib treatment for a non-leukemic indication
  • Major surgical procedures within 14 days of Day 1 administration of crenolanib.
  • Unwillingness or inability to comply with protocol.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01657682
Other Study ID Numbers  ICMJE ARO-005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Arog Pharmaceuticals, Inc.
Study Sponsor  ICMJE Arog Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jorge Cortes, MD M.D. Anderson Cancer Center
PRS Account Arog Pharmaceuticals, Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP