A Phase I Dose Escalation Study of Ibrutinib With Idarubicin/Cytarabine for Relapsed/Refractory Acute Myeloid Leukemia

Steven E. Coutre1 site in 1 country2 target enrollmentNovember 2016

Overview

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.

Registry

clinicaltrials.gov

Start Date

November 2016

End Date

November 10, 2017

Last Updated

7 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Steven E. Coutre

Responsible Party

Sponsor Investigator

Principal Investigator

Steven E. Coutre

Professor of Medicine

Stanford University

Eligibility Criteria

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arms & Interventions

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.

Intervention: Cytarabine

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.

Intervention: Ibrutinib

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.

Intervention: Idarubicin

Outcomes

Primary Outcomes

Induction Response Rate

Time Frame: 12 weeks

The induction Response Rate (CR/CRi) of ibrutinib in combination with idarubicin/cytarabine in relapsed/refractory AML was assessed as the number of participants who achieving a complete response (CR) or complete response with incomplete blood count recovery (CRi), divided by the total number of participants completing induction therapy.