Study of Ibrutinib in Subjects With Acute Myeloid Leukemia

NCT02351037 | Terminated Phase 2 Results

• 1 other identifier: PCYC-1131-CA
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 9

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)

Keywords

Acute Myeloid Leukemia; AML; Ibrutinib; Cytarabine; LD-AraC; Azacitidine

Outcome Measures

Primary Outcomes (2)

• Efficacy of Ibrutinib Monotherapy or in Combination With Either LD-AraC or Azacitidine Using the Overall Remission Rate (Defined as Proportion of Subjects Achieving a CR or CRi) According to the LeukemiaNet Guidelines

  Dohner's 2000 Criteria for AML: Complete Response (CR), Bone marrow blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \> 1.0 x 109/L (1000/µL); platelet count \>100 x 109/L (100 000/µL); independence of red cell transfusions; CR with Incomplete Recovery (CRi), All CR criteria except for residual neutropenia (\< 1.0 x 109/L \[1000/µL\]) or thrombocytopenia (\<100 x 109/L \[100 000/µL\]) ; Morphologic leukemia-free state, Bone marrow blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required; Partial Remission (PR), All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%; Relapse, Bone marrow blasts \> 5%; or reappearance of blasts in the blood; or development of extramedullary disease.

  When the last subject enrolled completes approximately 12 months of treatment.

• Safety and Tolerability of Ibrutinib Monotherapy or in Combination With Either LD-AraC or Azacitidine

  Number of Participants with Adverse Events and number of patients with lab abnormalities.The safety profile of ibrutinib was evaluated based on the incidence of adverse events (AEs) as well as clinically significant laboratory abnormalities and vital signs, and other malignancies. The safety evaluations performed in this study were standard and/or were required based on the safety data available from other clinical and preclinical settings.

  Up to 30 days following the last dose of study drug.

Secondary Outcomes (2)

• Relapse-free Survival (RFS), Event-free Survival (EFS) and Overall Survival (OS)

  When the last subject enrolled completes approximately 12 months of treatment

• Clinical Benefit Rate - as Defined as the Proportion of Subjects Who Achieve CR, CRi, Morphologic Leukemia-free State, or Partial Remission (PR)

  When the last subject enrolled completes approximately 12 months of treatment

Study Arms (3)

Ibrutinib Monotherapy Cohort

EXPERIMENTAL

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

Drug: Ibrutinib

Ibrutinib + LD-AraC Combination Cohort

EXPERIMENTAL

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.

Drug: Ibrutinib + LD-AraC

Ibrutinib+Azacitidine Combination Cohort

EXPERIMENTAL

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).

Drug: Ibrutinib+Azacitidine

Interventions

Ibrutinib DRUG

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

Also known as: Cohort 1

Ibrutinib Monotherapy Cohort

Ibrutinib + LD-AraC 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.

Also known as: Cohort 2

Ibrutinib + LD-AraC Combination Cohort

Ibrutinib+Azacitidine 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).

Also known as: Cohort 3

Ibrutinib+Azacitidine Combination Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pharmacyclics LLC.: lead

Study Sites (9)

City of Hope

Duarte, California, 91010, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Montefiore Einstein Center for Cancer Research

The Bronx, New York, 10461, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 26297574 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ibrutinib; KPNA1 protein, human

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Priyanka Mandava, Director of Clinical Operations
• Organization: Pharmacyclics

psingh@pcyc.com

408-215-3776

Study Officials

• Jorge Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2015
• First Posted: January 30, 2015
• Study Start: February 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: August 14, 2018
• Results First Posted: August 14, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)