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

NCT02635074 | Terminated Phase 1 DMC FDA Drug

• 5 other identifiers: HEMAML0036NCI-2015-0196135003IRB-35003P30CA124435
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Induction Response Rate

  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.

  12 weeks

Secondary Outcomes (1)

• Overall Survival (OS)

  6 months

Study Arms (1)

Treatment (ibrutinib, idarubicin, cytarabine)

EXPERIMENTAL

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.

Drug: Cytarabine; Drug: Ibrutinib; Drug: Idarubicin

Interventions

Cytarabine DRUG

Given IV

Also known as: 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

Treatment (ibrutinib, idarubicin, cytarabine)

Ibrutinib DRUG

Given PO

Also known as: Imbruvica, BTK Inhibitor PCI-32765, PCI-32765, CRA-032765

Treatment (ibrutinib, idarubicin, cytarabine)

Idarubicin DRUG

Given IV

Also known as: Idamycin, Zavedos, 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDR

Treatment (ibrutinib, idarubicin, cytarabine)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Steven E. Coutre: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University, School of Medicine

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; ibrutinib; Idarubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Steven Coutre

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: December 18, 2015
• Study Start: November 1, 2016
• Primary Completion: July 18, 2017
• Study Completion: November 10, 2017
• Last Updated: May 14, 2018

Record last verified: 2018-05

Locations

US (1)