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Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

This study is currently recruiting participants.
Verified March 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01132586
First received: May 26, 2010
Last updated: March 26, 2013
Last verified: March 2013
History of Changes
  Purpose

This phase I trial is studying the side effects and best dose of lenalidomide when given together with cytarabine and idarubicin in treating patients with acute myeloid leukemia. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as cytarabine and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cytarabine and idarubicin may kill more cancer cells.


Condition Intervention Phase
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Recurrent Adult Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
 Drug: lenalidomide
Drug: cytarabine
Drug: idarubicin
Other: pharmacological study
Other: laboratory biomarker analysis
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Lenalidomide and Conventional Chemotherapy in Acute Myeloid Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD of lenalidomide, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Qualitative and quantitative toxicities, graded using NCI CTCAE version 4.0 [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
  • Therapeutic response, assessed using International Working Group criteria [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: No ]
  • Pharmacodynamic studies, including micro-ribonucleic acid (miRNA)-181 family and target gene expression, CCAAT/enhancer binding protein (C/EBP), alpha gene (CEBPA) expression, and genes involved in erythroid differentiation [ Time Frame: Baseline, day 5, and day 28 ] [ Designated as safety issue: No ]

Estimated Enrollment: 61
Study Start Date: May 2010
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (lenalidomide, cytarabine, idarubicin)

INDUCTION:

COHORT I: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on days 5-7.

COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 24 hours on days 5-11, and idarubicin as above.

Patients with residual disease on day 18 undergo a second course of induction therapy.

CONSOLIDATION:

COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days 5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

 Drug: lenalidomide
Given orally
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: idarubicin
Given IV
Other Names:
  • 4-demethoxydaunorubicin
  • 4-DMDR
  • DMDR
  • IDA
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of lenalidomide in combination with conventional chemotherapy in two separate cohorts of patients with 1) relapsed or refractory acute myeloid leukemia (AML) and 2) age >= 60 with untreated AML and recommend starting doses for phase II studies of this combination of agents.

SECONDARY OBJECTIVES:

I. To define the qualitative and quantitative toxicities of these combinations of agents in regard to organ specificity, time course, predictability, and reversibility.

II. To document the therapeutic response of these combinations of agents in patients with poor risk AML.

III. To conduct pharmacodynamic studies to investigate the potential mechanism of lenalidomide activity in this trial.

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

INDUCTION:

COHORT I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21, cytarabine IV continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on days 5-7.

COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 24 hours on days 5-11, and idarubicin as above.

Patients with residual disease on day 18 undergo a second course of induction therapy.

CONSOLIDATION:

COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days 5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.

COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cohort 1: Patients must be age >18 and < 65 with relapsed or refractory AML or high risk myelodysplastic syndrome (MDS); high risk MDS is defined as international prognosis scoring system (IPSS) score of 1.5 or higher; eligible patients will have a score of 1.5 or higher at any time from diagnosis to screening

    • Cohort 2: Patients must be age > 18 with previously untreated AML; favorable risk AML patients < 60 years of age are excluded; these are defined as core binding factor (CBF) AML patients and characterized by cytogenetic or molecular evidence of CBF leukemia; untreated AML patients < 60 years of age must be negative on screening for CBF leukemia by cytogenetic or molecular analysis (Note: Prior therapy for MDS is permitted)
  • Patients with secondary AML or therapy-related AML are eligible
  • No granulocytic sarcoma as the sole site of disease
  • No advanced malignant solid tumors or additional active hematologic malignancies
  • No active central nervous system (CNS) disease
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Total bilirubin < 2.0 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 times upper limit of normal
  • Creatinine < 2.0 mg/dL AND creatinine clearance > 50 mL/min
  • Left ventricular ejection fraction (LVEF) ≥ 40%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception (one highly effective method and one additional effective method) for ≥ 28 days before, during, and for ≥ 28 days after completion of study treatment

  • Patients with active infection are eligible provided the infection is under control

    • Patients with uncontrolled infection may be enrolled after the infection is treated and brought under control
  • Patients with a comorbid medical illness are eligible provided their life expectancy attributed to the illness is > 6 months
  • No comorbidities that would preclude safety evaluation of study treatment

  • No uncontrolled concurrent illness including, but not limited to, any of the following:

    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Serious cardiac arrhythmia
    • Psychiatric illness or social situations that would limit compliance with study requirements
    • Myocardial infarction within the past 6 months
    • NYHA class III-IV heart failure
    • Severe uncontrolled ventricular arrhythmias
    • Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • No serious medical or psychiatric illness that would interfere with study participation
  • No known HIV positivity
  • No history of medically serious allergic reactions or non-hematologic toxicities attributed to the agents in this study such as lenalidomide or thalidomide or compounds of similar chemical or biologic composition that are not easily managed, or patients with a history of cerebellar toxicity to cytarabine
  • No history of neurologic toxicity with cytarabine
  • Prior lenalidomide, cytarabine, and/or idarubicin allowed provided that the combination of the 3 agents has never before been administered and that no lenalidomide has been administered for ≥ 6 months
  • Recovered from the adverse events due to agents administered > 4 weeks ago
  • More than 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
  • At least 14 days since prior and no other concurrent investigational agents
  • No concurrent palliative radiotherapy
  • No other concurrent commercial agents or therapies administered with the intent to treat the patient's leukemia
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01132586

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Richard M. Stone     866-790-4500     rstone@partners.org    
Principal Investigator: Richard M. Stone            
United States, Ohio
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: William G. Blum     614-293-9165     william.blum@osumc.edu    
Principal Investigator: William G. Blum            
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: William Blum Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01132586     History of Changes
Other Study ID Numbers: NCI-2011-01375, OSU 10016, OSU-10016, CDR0000673883, U01CA076576
Study First Received: May 26, 2010
Last Updated: March 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Thalidomide
Lenalidomide
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
 Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Leprostatic Agents
Anti-Bacterial Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on May 19, 2013