Ibrutinib, Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT ID: NCT02635074

Last Updated: 2018-05-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2017-11-10

Brief Summary

This phase I trial studies the side effects and best dose of ibrutinib when given together with idarubicin and cytarabine in treating patients with acute myeloid leukemia that has returned after a period of improvement or has not responded to previous treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib together with idarubicin and cytarabine may kill more cancer cells.

Detailed Description

PRIMARY OBJECTIVES:

Identify the safety and recommended phase 2 dose of ibrutinib in combination with idarubicin/cytarabine in relapsed/refractory acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

• Assess the induction response rate (complete remission [CR]/complete remission with incomplete count [CRi]) of ibrutinib in combination with idarubicin/cytarabine in relapsed/refractory AML.
• Assess overall survival of ibrutinib in combination with idarubicin/cytarabine in relapsed/refractory AML.

OUTLINE: This is a dose-escalation study of ibrutinib.

INDUCTION: Patients receive ibrutinib orally (PO) once daily (QD) on days 1 to 21, idarubicin intravenously (IV) over 15 minutes on days 1 to 3 and cytarabine IV continuously on days 1 to 4.

CONSOLIDATION: Patients achieving CR or CRi may receive ibrutinib PO QD on days 1 to 21, idarubicin IV over 15 minutes on Days 1and 2 and cytarabine IV continuously on days 1-3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients maintaining a CR/CRi may receive ibrutinib PO QD on days 1 to 28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 6 months.

Conditions

Recurrent Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (ibrutinib, idarubicin, cytarabine)

INDUCTION: Ibrutinib daily on days 1 to 21, idarubicin intravenously (IV) over 15 minutes on days 1 to 3 and cytarabine IV continuously on days 1 to 4.

CONSOLIDATION: Patients achieving CR or CRi may receive ibrutinib daily on days 1 to 21, idarubicin IV over 15 minutes on days 1 to 2 and cytarabine IV continuously on days 1 to 3. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients maintaining a CR/CRi may receive ibrutinib daily on days 1 to 28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

Given IV

Ibrutinib

Intervention Type: DRUG

Given PO

Idarubicin

Intervention Type: DRUG

Given IV

Interventions

Cytarabine

Given IV

Intervention Type: DRUG

Ibrutinib

Given PO

Intervention Type: DRUG

Idarubicin

Given IV

Intervention Type: DRUG

Other Intervention Names

Beta-cytosine arabinoside; 1-beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-beta-D-arabinofuranosylcytosine; 2(1H)-pyrimidinone, 4-amino-1-beta-d-arabinofuranosyl; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosar-U; Cytosine Arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Imbruvica; BTK Inhibitor PCI-32765; PCI-32765; CRA-032765; Idamycin; Zavedos; 4-Demethoxydaunomycin; 4-Demethoxydaunorubicin; 4-DMDR

Eligibility Criteria

Inclusion Criteria

• Previous morphologically-confirmed diagnosis of acute myeloid leukemia (AML) based on World Health Organization (WHO) Criteria
• At least one prior chemotherapy regimen to treat AML
• Disease relapse or refractory disease as shown by > 5% blasts in the bone marrow (not attributable to another cause). Administration of hydrea to control high WBC count is permitted.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, or Karnofsky Performance Status (KPS) ≥ 60%
• Life expectancy > 4 weeks
• Platelet count ≥ 10,000/mm3 within 72 hours of initiating the Induction Cycle (platelet transfusion support is allowed)
• Serum creatinine ≤ 2.0 mg/dL within 72 hours of initiating the Induction Cycle
• Total bilirubin ≤ 2.1 mg/dL within within 72 hours of initiating the Induction Cycle (EXCEPTION: If elevation is not due to liver dysfunction, and is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome, or hemolysis of non-hepatic origin)
• Serum glutamic oxaloacetic transaminase (SGOT) [aspartate aminotransferase (AST) ] ≤ 3.0 X upper limit of normal (ULN) within 72 hours of initiating the Induction Cycle
• Serum glutamic pyruvic transaminase (SGPT) [alanine aminotransferase (ALT)] ≤ 3.0 X ULN within 72 hours of initiating the Induction Cycle
• Baseline prothrombin time (PT)/international normalized ratio (INR) ratio < 3 X ULN within 7 days of initiating the Induction Cycle (for subjects with correctable coagulation abnormalities, coagulation factor support per institutional standard of care for AML is allowed)
• Partial thromboplastin time (PTT) < 3 X ULN within 7 days of initiating the Induction Cycle (for subjects with correctable coagulation abnormalities, coagulation factor support per institutional standard of care for AML is allowed)
• Negative pregnancy test within 14 days prior to study treatment (for Women of reproductive potential only)
• Women of child-bearing potential and men must agree (in ICF) to use adequate contraception (eg, hormonal or barrier methods of birth control; abstinence; sterilized partner) for the duration of study participation
• Ability to understand and the willingness to sign the written informed consent document

Exclusion Criteria

• Received anticancer therapy (chemotherapy, immunotherapy, radiotherapy, or investigational therapy) within 2 weeks prior to starting study treatment [EXCEPTION: Hydroxyurea (hydrea) to control high white blood cell count is permitted]
• Receiving any other investigational agents within 14 days or 5 effective half lives (whichever is shorter) prior to 1st dose of ibrutinib
• Prior treatment with ibrutinib
• Known acute promyelocytic leukemia (French-American-British Class M3-AML)
• Known active central nervous system (CNS) leukemia
• Prior bone marrow transplant presenting with active uncontrolled graft vs host disease (GvHD)
• Known congenital bleeding disorders, such as hemophilia
• Known history of stroke or intracranial hemorrhage within 6 months prior to study treatment
• Concomitant use of warfarin or other vitamin K antagonists
• Requires treatment with strong CYP3A inhibitors at the time of study enrollment. Washout period is 5 effective half-lives is required prior to 1st dose of ibrutinib
• Requires treatment with strong CYP3A inducers at the time of study enrollment. Washout period is 5 effective half-lives is required prior to 1st dose of ibrutinib
• Known active uncontrolled systemic infection
• Major surgery within 4 weeks of 1st dose of ibrutinib
• Unable to swallow capsules
• Known Malabsorption syndrome
• Known Disease significantly affecting gastrointestinal function
• Resection of the stomach or small bowel
• Uncontrolled symptomatic inflammatory bowel disease
• Ulcerative colitis
• Bowel obstruction, partial or complete
• Congestive heart failure with ejection fraction (EF) < 45%
• Uncontrolled cardiac disease, including uncontrolled cardiac arrhythmia or coronary artery disease (CAD) with active symptoms due to CAD defined as unstable angina
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib; idarubicin; or cytarabine
• Uncontrolled intercurrent illness including, but not limited to:
• Active infection
• Psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant
• Lactating
• Known positive HIV
• Known active hepatitis C
• 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

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Steven E. Coutre

OTHER

Sponsor Role: lead

Responsible Party

Steven E. Coutre

Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Steven Coutre

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University, School of Medicine

Palo Alto, California, United States

Countries

United States

Other Identifiers

NCI-2015-01961

Identifier Type: REGISTRY

Identifier Source: secondary_id

35003

Identifier Type: -

Identifier Source: secondary_id

IRB-35003

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA124435

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HEMAML0036

Identifier Type: -

Identifier Source: org_study_id