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

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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.

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.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Acute Myeloid Leukemia (AML) Drug: Crenolanib Drug: Mitoxantrone Drug: Cytarabine Drug: Etoposide Drug: Fludarabine Drug: G-CSF Drug: Idarubicin Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Crenolanib Combined With Standard Salvage Chmetherapy in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
Actual Study Start Date : February 2016
Actual Primary Completion Date : February 2018
Actual Study Completion Date : February 2018


Arm Intervention/treatment
Experimental: Arm A
  • Mitoxantrone
  • Cytarabine
  • Crenolanib
Drug: Crenolanib
Drug: Mitoxantrone
Drug: Cytarabine
Other Name: cytosine arabinoside

Experimental: Arm B
  • Mitoxantrone
  • Etoposide
  • Cytarabine
  • Crenolanib
Drug: Crenolanib
Drug: Mitoxantrone
Drug: Cytarabine
Other Name: cytosine arabinoside

Drug: Etoposide
Other Name: Etoposide phosphate

Experimental: Arm C
  • Fludarabine
  • Cytarabine
  • G-CSF
  • Idarubicin
  • Crenolanib
Drug: Crenolanib
Drug: Cytarabine
Other Name: cytosine arabinoside

Drug: Fludarabine
Other Name: Fludarabine monophosphate

Drug: G-CSF
Drug: Idarubicin



Primary Outcome Measures :
  1. 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



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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. 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

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): NCT02626338


Locations
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United States, Arkansas
University of Arkansas
Little Rock, Arkansas, United States, 72205
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
Houston Methodist
Houston, Texas, United States, 77030
Sponsors and Collaborators
Arog Pharmaceuticals, Inc.

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Responsible Party: Arog Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02626338     History of Changes
Other Study ID Numbers: ARO-011
First Posted: December 10, 2015    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Vidarabine
Cytarabine
Fludarabine
Fludarabine phosphate
Etoposide
Etoposide phosphate
Mitoxantrone
Idarubicin
Crenolanib
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Analgesics
Sensory System Agents
Peripheral Nervous System Agents