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Pilot Study of Crenolanib Combined With Standard Salvage Chemotherapy in Subjects With R/R AML

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: NCT02626338
Recruitment Status : Completed
First Posted : December 10, 2015
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
Arog Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE November 18, 2015
First Posted Date  ICMJE December 10, 2015
Last Update Posted Date May 14, 2019
Actual Study Start Date  ICMJE February 2016
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 21, 2016)
To determine the safety, dose-limiting toxicities and maximum tolerated dose (or confirm the target dose of 100 mg TID) of crenolanib given sequentially following standard salvage chemotherapy regimens in subjects with refractory/relapsed AML. [ Time Frame: 35 days ]
DLT will be defined as any clinically significant adverse event or abnormal laboratory value that is not related to concomitant medications, co-morbidities or underlying disease (leukemia), and that is not expected for the chemotherapy being used together with crenolanib
Original Primary Outcome Measures  ICMJE
 (submitted: December 8, 2015)
To determine the safety and tolerability: Number of participants with Dose-Limiting Toxicity (using CTCAE v4.03) until the maximum tolerated has been identified for crenolanib in combination with mitoxantrone and cytarabine. [ Time Frame: 35 days ]
DLT will be defined as any clinically significant adverse event or abnormal laboratory value that is not related to concomitant medications, co-morbidities or underlying disease (leukemia), and that is not expected for the chemotherapy being used together with crenolanib
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study of Crenolanib Combined With Standard Salvage Chemotherapy in Subjects With R/R AML
Official Title  ICMJE Pilot Study of Crenolanib Combined With Standard Salvage Chmetherapy in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
Brief Summary The proposed study is designed to combine crenolanib with standard salvage chemotherapy to treat patients with R/R AML irrespective the FLT3 status.
Detailed Description Open label, dose de-escalation, pilot trial of crenolanib with standard salvage chemotherapy. Subjects may receive up to 2 cycles of induction with standard salvage chemotherapy followed by crenolanib. Each arm will enroll approximately 24 patients (72 total); stratification to each arm will be per physician's choice
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed/Refractory Acute Myeloid Leukemia (AML)
Intervention  ICMJE
  • Drug: Crenolanib
  • Drug: Mitoxantrone
  • Drug: Cytarabine
    Other Name: cytosine arabinoside
  • Drug: Etoposide
    Other Name: Etoposide phosphate
  • Drug: Fludarabine
    Other Name: Fludarabine monophosphate
  • Drug: G-CSF
  • Drug: Idarubicin
Study Arms  ICMJE
  • Experimental: Arm A
    • Mitoxantrone
    • Cytarabine
    • Crenolanib
    Interventions:
    • Drug: Crenolanib
    • Drug: Mitoxantrone
    • Drug: Cytarabine
  • Experimental: Arm B
    • Mitoxantrone
    • Etoposide
    • Cytarabine
    • Crenolanib
    Interventions:
    • Drug: Crenolanib
    • Drug: Mitoxantrone
    • Drug: Cytarabine
    • Drug: Etoposide
  • Experimental: Arm C
    • Fludarabine
    • Cytarabine
    • G-CSF
    • Idarubicin
    • Crenolanib
    Interventions:
    • Drug: Crenolanib
    • Drug: Cytarabine
    • Drug: Fludarabine
    • Drug: G-CSF
    • Drug: Idarubicin
Publications * Not Provided

*   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
Actual Enrollment  ICMJE
 (submitted: May 8, 2019)
16
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2015)
24
Actual Study Completion Date  ICMJE February 2018
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Confirmed diagnosis of AML, including treatment-related secondary AML (except prior MDS) according to World Health Organization (WHO) 2008 classification at treating institution
  2. Subjects who are refractory* or who have relapsed** following first line AML therapy with cytarabine/anthracycline based chemotherapy, with or without a tyrosine kinase inhibitor. *Refractory to induction therapy is defined as never achieving CR, CRi or CRp (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI.

    or

    **First relapse is defined as untreated hematologic relapse (according to International Working Group criteria) after one line of intensive regimen for AML (re-induction, consolidation and/or transplant allowed) including at least one cytarabine containing induction block with a total dose no less than 700mg/m² per cycle and 3 days of an anthracycline with or without a TKI that induced a CR/CRi/CRp. Subjects are allowed to receive induction, consolidation, transplant and/or maintenance prior to achieving their first CR/CRi/CRp.

  3. Subjects considered eligible for intensive chemotherapy
  4. ECOG performance status ≤ 2
  5. Age ≥ 18 years
  6. Adequate liver function within 72 hours of enrollment, defined as:

    • Normal total serum bilirubin
    • ALT and AST ≤ 2.0 x ULN
  7. Adequate renal function, defined as serum creatinine ≤ 1.5x ULN
  8. Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 72 hours prior to enrollment "Woman of childbearing potential" is defined as any woman who has not undergone a hysterectomy and who has had menses at any time in the preceding 24 consecutive months
  9. Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin one acceptable method of birth control (IUD, tubal ligation, or partner's vasectomy) while on crenolanib and for 3 months following the last dose of crenolanib. Hormonal contraception alone is not an acceptable method of birth control for the purpose of this trial.
  10. Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy and must agree to avoid to father a child (while on therapy and for 3 month after the last dose of crenolanib).
  11. Willing to adhere to protocol specific requirements 12. Following receipt of verbal and written information about the study, the subject must provide signed informed consent before any study related activity is carried out. 13. Clinically significant toxic effects of prior therapy (expect hydroxyuria) resolved to Grade ≤ 1 before the start of study.

Exclusion Criteria

  1. < 5% blasts in blood or marrow at screening, except if measurable extramedullary AML is confirmed
  2. Acute promyelocytic leukemia (APL)
  3. Known clinically active CNS leukemia
  4. Clinically active or unstable graft-versus-host disease (GvHD) requiring treatment which precludes administration of chemotherapy as defined in this protocol
  5. Prior anti-leukemia therapy within 14 days of enrollment for classical cytotoxic agents, and within 5x the half-life for other investigational agents

    • Prior use of hydroxyurea or isolated doses of cytarabine for palliation (i.e., control of WBC) are allowed but should be discontinued at least 24 hrs prior to enrollment.
    • Other agents used strictly with palliative intent might be allowed during this period after discussing with principal investigator
  6. Pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
  7. Known HIV infection.
  8. Evidence of ongoing, uncontrolled systemic infection or an uncontrolled local infection requiring therapy at the start of study.
  9. "Currently active" second malignancy (other than non-melanoma skin cancer, carcinoma in situ of the cervix or prostatic intraepithelial neoplasia within 1 year). Subjects are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within 1 year.
  10. Concurrent participation in another therapeutic clinical trial.
  11. Pregnant or breastfeeding women
  12. Subjects of childbearing potential not willing to use adequate contraception during study and 3 months after last dose of crenolanib
  13. Subject with uncontrolled cardiac disease including congestive heart failure class III or IV by the NYHA, unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
  14. Subject with concurrent severe and/or uncontrolled medical or psychiatric conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
  15. Inability to give an informed consent
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 NCT02626338
Other Study ID Numbers  ICMJE ARO-011
Has Data Monitoring Committee No
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 Not Provided
PRS Account Arog Pharmaceuticals, Inc.
Verification Date May 2019

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