Study of Crenolanib Combined With Chemotherapy in FLT3-mutated Acute Myeloid Leukemia Patients
Primary Purpose
Acute Myeloid Leukemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Crenolanib besylate
Idarubicin
Cytarabine
Azacytidine
Mitoxantrone
Etoposide
Fludarabine
G-CSF
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of refractory/relapsed AML or high-risk MDS
- Arm 1: Subjects must have received at least one prior therapy and a maximum of three prior therapies
- Arm 2: Subjects must have received at least one prior therapy and a maximum of three prior therapies. No prior treatment with 5-Azacitidine is allowed in this arm.
- FLT3 mutation positive (ITD, TKD or other)
- ECOG PS 0-2
- Adequate liver and renal function
- Negative pregnancy test
- Extramedullary leukemia allowed except CNS disease
Exclusion Criteria:
Arm 1 and 2 Exclusion:
- <5% blasts in marrow or blood at time of screening
- Active HIV, hepatitis B or C
- CNS leukemia
- Clinically significant GVHD or organ dysfunction where chemotherapy specified by protocol cannot be given
- Patient with AML-M3 (APL)
- Pre-existing liver diseases (i.e. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
Sites / Locations
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm 1 crenolanib besylate combination
Arm 2 crenolanib besylate combination
Arm Description
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
Arm 2 patients will receive crenolanib besylate and azacytidine.
Outcomes
Primary Outcome Measures
Dose-limiting toxicities of crenolanib besylate combination therapy
Response rate of crenolanib besylate combination therapy
Secondary Outcome Measures
Duration of response
Progression free survival
Overall survival
Full Information
NCT ID
NCT02400281
First Posted
March 18, 2015
Last Updated
July 17, 2020
Sponsor
Arog Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02400281
Brief Title
Study of Crenolanib Combined With Chemotherapy in FLT3-mutated Acute Myeloid Leukemia Patients
Official Title
Phase I-II Study of Crenolanib Combined With Standard Salvage Chemotherapy, and Crenolanib Combined With 5-Azacitidine in Acute Myeloid Leukemia Patients With FLT3 Activating Mutations
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
September 2015 (undefined)
Primary Completion Date
July 15, 2020 (Actual)
Study Completion Date
July 15, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arog Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open label, two-arm, Phase I-II trial, non-randomized. Arm 1: crenolanib with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin) Arm 2: crenolanib with 5-azacitidine
Detailed Description
For each arm:
The phase I with dose-limiting toxicity (DLT) determination will use 3+3 design.
Phase II total of 52 patients (26 per arm) will be treated at established phase I dose.
Enrollment to be simultaneous to each arm.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 crenolanib besylate combination
Arm Type
Experimental
Arm Description
Arm 1 patients will receive crenolanib besylate, combined with standard chemotherapy (Idarubicin/Cytarabine, MEC;Mitoxantrone/Etoposide/Cytarabine, FLAG-Ida: Fludarabine/Cytarabine/G-CSF/Idarubicin
Arm Title
Arm 2 crenolanib besylate combination
Arm Type
Experimental
Arm Description
Arm 2 patients will receive crenolanib besylate and azacytidine.
Intervention Type
Drug
Intervention Name(s)
Crenolanib besylate
Other Intervention Name(s)
CP-868,596-26
Intervention Type
Drug
Intervention Name(s)
Idarubicin
Other Intervention Name(s)
4-demethoxydaunorubicin
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
cytosine arabinoside
Intervention Type
Drug
Intervention Name(s)
Azacytidine
Other Intervention Name(s)
5-azacytidine
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Other Intervention Name(s)
Novantrone
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
etoposide phosphate
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
G-CSF
Primary Outcome Measure Information:
Title
Dose-limiting toxicities of crenolanib besylate combination therapy
Time Frame
6 months
Title
Response rate of crenolanib besylate combination therapy
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Duration of response
Time Frame
2 years
Title
Progression free survival
Time Frame
2 years
Title
Overall survival
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of refractory/relapsed AML or high-risk MDS
Arm 1: Subjects must have received at least one prior therapy and a maximum of three prior therapies
Arm 2: Subjects must have received at least one prior therapy and a maximum of three prior therapies. No prior treatment with 5-Azacitidine is allowed in this arm.
FLT3 mutation positive (ITD, TKD or other)
ECOG PS 0-2
Adequate liver and renal function
Negative pregnancy test
Extramedullary leukemia allowed except CNS disease
Exclusion Criteria:
Arm 1 and 2 Exclusion:
<5% blasts in marrow or blood at time of screening
Active HIV, hepatitis B or C
CNS leukemia
Clinically significant GVHD or organ dysfunction where chemotherapy specified by protocol cannot be given
Patient with AML-M3 (APL)
Pre-existing liver diseases (i.e. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jorge Cortes, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Crenolanib Combined With Chemotherapy in FLT3-mutated Acute Myeloid Leukemia Patients
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