Study of Ibrutinib in Subjects With Acute Myeloid Leukemia

NCT ID: NCT02351037

Last Updated: 2018-08-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2017-04-30

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and tolerability of ibrutinib alone or in combination with either cytarabine or azacitidine in the treatment of subjects with Acute Myeloid Leukemia (AML) who have failed standard treatment, or subjects without prior therapy who refuse standard chemotherapy.

Conditions

Acute Myeloid Leukemia (AML)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ibrutinib Monotherapy Cohort

Up to 33 response evaluable subjects will receive ibrutinib 560 mg once daily on a continuous basis.

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

Subjects will receive ibrutinib 560 mg once daily on a continuing basis.

Ibrutinib + LD-AraC Combination Cohort

Up to 25-28 additional response evaluable subjects (for a total of 34 subjects) will receive ibrutinib 560 mg once daily on a continuous basis starting 2 days prior to first cytarabine dose (20 mg BID sc) for 10 days of a 28-day cycle.

Group Type: EXPERIMENTAL

Ibrutinib + LD-AraC

Intervention Type: DRUG

Subjects will receive ibrutinib 560 mg once daily on a continuous basis starting 2 days prior to first cytarabine dose (20 mg BID sc) for 10 days of a 28-day cycle.

Ibrutinib+Azacitidine Combination Cohort

Up to 34 response evaluable subjects will receive ibrutinib 560 mg once daily on a continuous basis starting 1 day prior to first azacitidine dose + azacitidine 75mg/m2 IV once daily Days 1-7 of a 28-day cycle (with an option to increase to 100mg/m2 after 2 cycles).

Group Type: EXPERIMENTAL

Ibrutinib+Azacitidine

Intervention Type: DRUG

Subjects will receive ibrutinib 560 mg once daily on a continuous basis starting 1 day prior to first azacitidine dose + azacitidine 75 mg/m2 IV once daily on Days 1-7 of a 28-day cycle (with an option to increase to 100 mg/m2 after 2 cycles).

Interventions

Ibrutinib

Subjects will receive ibrutinib 560 mg once daily on a continuing basis.

Intervention Type: DRUG

Ibrutinib + LD-AraC

Subjects will receive ibrutinib 560 mg once daily on a continuous basis starting 2 days prior to first cytarabine dose (20 mg BID sc) for 10 days of a 28-day cycle.

Intervention Type: DRUG

Ibrutinib+Azacitidine

Subjects will receive ibrutinib 560 mg once daily on a continuous basis starting 1 day prior to first azacitidine dose + azacitidine 75 mg/m2 IV once daily on Days 1-7 of a 28-day cycle (with an option to increase to 100 mg/m2 after 2 cycles).

Intervention Type: DRUG

Other Intervention Names

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

Inclusion Criteria

• Male and female ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Subjects with pathologically documented AML that has failed standard treatment, or subjects without prior therapy who refuse standard treatment options
• Bone marrow aspirate/biopsy results showing >5% blasts
• WBC count <25,000 cells/mm3 (25 x 109/L)
• Platelet count >10,000 cells/mm3 (10 x 109/L)
• Adequate hepatic and renal function defined as:

• For Cohorts 1 and 2: serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤3.0 x upper limit of normal (ULN); for Cohort 3: ALT ≤2.5 or AST ≤2.5 ULN.
• Serum creatinine ≤2 mg/dL or Estimated Creatinine Clearance ≥30 mL/min (Cockcroft-Gault).
• Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin).
• PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN (When treated with warfarin or other vitamin K antagonists, then INR ≤3.0).
• Female subjects who are of non-reproductive potential (Female subjects of reproductive potential must have a negative serum pregnancy test upon study entry).
• Male and female subjects of reproductive potential agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug.

Exclusion Criteria

• Acute promyelocytic leukemia (French-American-British Class M3 AML).
• Known active central nervous system (CNS) leukemia.
• Known active systemic infection (Grade ≥2).
• Active bleeding disorders or clinical signs of bleeding (Grade ≥2).
• Prior bone marrow transplant that requires immunosuppressant therapy or presents with graft vs host disease (GVHD).
• History of other malignancies, except:

• Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and with low risk of recurrence by treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Prior treatment with a BTK inhibitor.
• For Cohort 3 subjects, prior treatment with hypomethylating agents (eg, azacitidine, decitabine)
• Anticancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy within 14 days or 5 half-lives (whichever is shorter) prior to first dose of study drug.
• Subject has received a monoclonal antibody for anticancer intent within 8 weeks prior to the first dose of study drug.
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
• Recent infection requiring intravenous (IV) systemic treatment that was completed ≤14 days before the first dose of study drug.
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
• Major surgery within 4 weeks of first dose of study drug.
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
• Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
• Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
• Concomitant use of warfarin or other Vitamin K antagonists.
• Requires treatment or prophylaxis with a strong cytochrome P450 (CYP) 3A inhibitor
• Currently active, clinically significant hepatic impairment (≥ moderate hepatic impairment according to the Child Pugh classification).
• Lactating or pregnant.
• Unwilling or unable to participate in all required study evaluations and procedures.
• Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jorge Cortes, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

City of Hope

Duarte, California, United States

UC Davis Medical Center

Sacramento, California, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Montefiore Einstein Center for Cancer Research

The Bronx, New York, United States

MD Anderson Cancer Center

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

References

Wilken R, Li CS, Sharon VR, Kim K, Patel FB, Patel F, Maverakis E. Topical clobetasol for the treatment of toxic epidermal necrolysis: study protocol for a randomized controlled trial. Trials. 2015 Aug 22;16:374. doi: 10.1186/s13063-015-0879-7.

Reference Type: DERIVED

PMID: 26297574 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PCYC-1131-CA

Identifier Type: -

Identifier Source: org_study_id