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Trial record 5 of 253 for:    IDARUBICIN

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

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ClinicalTrials.gov Identifier: NCT02635074
Recruitment Status : Terminated (safety)
First Posted : December 18, 2015
Last Update Posted : May 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Steven E. Coutre, Stanford University

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.

Condition or disease Intervention/treatment Phase
Recurrent Adult Acute Myeloid Leukemia Drug: Cytarabine Drug: Ibrutinib Drug: Idarubicin Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of Ibrutinib With Idarubicin/Cytarabine for Relapsed/Refractory Acute Myeloid Leukemia
Study Start Date : November 2016
Actual Primary Completion Date : July 18, 2017
Actual Study Completion Date : November 10, 2017


Arm Intervention/treatment
Experimental: 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.

Drug: Cytarabine
Given IV
Other 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

Drug: Ibrutinib
Given PO
Other Names:
  • Imbruvica
  • BTK Inhibitor PCI-32765
  • PCI-32765
  • CRA-032765

Drug: Idarubicin
Given IV
Other Names:
  • Idamycin
  • Zavedos
  • 4-Demethoxydaunomycin
  • 4-Demethoxydaunorubicin
  • 4-DMDR




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 6 months ]
    Overall survival (OS) was assessed as the number of patients remaining alive 6 months after the initiation of study therapy



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 unresolved toxicities due to prior anticancer therapy [≥ Grade 2, by Common Terminology Criteria for Adverse Events (CTCAE) v4.03] unless otherwise defined in the inclusion/exclusion criteria (EXCEPTION: alopecia)
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02635074


Locations
United States, California
Stanford University, School of Medicine
Palo Alto, California, United States, 94304
Sponsors and Collaborators
Steven E. Coutre
National Cancer Institute (NCI)
Investigators
Principal Investigator: Steven Coutre Stanford University

Responsible Party: Steven E. Coutre, Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT02635074     History of Changes
Other Study ID Numbers: HEMAML0036
NCI-2015-01961 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
35003
IRB-35003 ( Other Identifier: Stanford IRB )
P30CA124435 ( U.S. NIH Grant/Contract )
First Posted: December 18, 2015    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Idarubicin
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors