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Daunorubicin and Cytarabine With or Without Zosuquidar Trihydrochloride in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or Refractory Anemia
This study is ongoing, but not recruiting participants.
First Received: October 3, 2002   Last Updated: February 6, 2009   History of Changes
Sponsor: Eastern Cooperative Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00046930
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Zosuquidar trihydrochloride may help daunorubicin and cytarabine kill more cancer cells by making cancer cells more sensitive to the drugs. It is not yet known whether daunorubicin and cytarabine are more effective with or without zosuquidar trihydrochloride in treating acute myeloid leukemia or anemia.

PURPOSE: This randomized phase III trial is studying how well giving zosuquidar trihydrochloride together with daunorubicin and cytarabine works compared to daunorubicin and cytarabine alone in treating older patients with newly diagnosed acute myeloid leukemia or anemia that has not responded to previous treatment.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
 Biological: filgrastim
Biological: sargramostim
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: zosuquidar trihydrochloride
 Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control
Official Title: A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride (LY335979), During Conventional Induction and Post-Remission Therapy in Patients Greater Than 60 Years of Age With Newly Diagnosed Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts in Transformation or High-Risk Refractory Anemia With Excess Blasts

Resource links provided by NLM:

MedlinePlus related topics: Anemia Cancer Leukemia, Adult Acute Leukemia, Adult Chronic
Drug Information available for: Cytarabine hydrochloride Daunorubicin Daunorubicin hydrochloride Filgrastim Sargramostim Zosuquidar Zosuquidar Trihydrochloride Cytarabine
U.S. FDA Resources

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

Study Start Date: July 2002
Detailed Description:

OBJECTIVES:

  • Compare the overall survival and progression-free survival of elderly patients with newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts (RAEB) in transformation, or high-risk RAEB treated with daunorubicin and cytarabine with or without zosuquidar trihydrochloride.
  • Compare the complete remission rate of patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.
  • Compare the systemic exposure of daunorubicin and cytarabine in patients treated with zosuquidar trihydrochloride vs placebo.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (60-69 years vs 70 years and over), disease (refractory anemia with excess blasts [RAEB] vs RAEB in transformation or acute myeloid leukemia [AML]), and disease type (de novo vs secondary). Patients are randomized to 1 of 2 treatment arms.

  • Induction:

    • Arm I: Patients receive daunorubicin IV over 10-15 minutes and zosuquidar trihydrochloride IV over 6 hours on days 1-3. Patients also receive cytarabine IV continuously on days 1-7.
    • Arm II: Patients receive daunorubicin and cytarabine as in arm I. Patients also receive placebo IV over 6 hours on days 1-3.

Beginning on day 12, patients who achieve aplasia receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) or IV daily until blood counts recover. Patients who have evidence of persistent AML are eligible to receive a second identical course of induction chemotherapy.

  • Consolidation I (beginning within 8 weeks after documentation of complete remission [CR] or measurable remission [MR]): Patients who achieve a CR or MR receive cytarabine IV over 1 hour once or twice daily on days 1-6 and GM-CSF or G-CSF SC or IV beginning on day 7 and continuing until blood counts recover.
  • Consolidation II: Patients who have maintained peripheral blood evidence of a remission receive daunorubicin, cytarabine, and zosuquidar trihydrochloride or placebo as in induction chemotherapy. Patients also receive GM-CSF or G-CSF SC or IV beginning on day 8 or after last cytarabine dose and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 450 patients (225 per treatment arm) will be accrued for this study within 4.1 years.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts (RAEB) in transformation (RAEB-T), or high-risk RAEB

    • AML with 30% myeloblasts on bone marrow aspirate or peripheral blood differential

      • Any FAB subtype except M3 (i.e., acute promyelocytic leukemia)
    • RAEB with 11-20% myeloblasts on bone marrow aspirate or peripheral blood differential, provided there are other criteria for high-risk disease
    • RAEB-T with 21-30% myeloblasts on bone marrow aspirate or peripheral blood differential
  • No blastic transformation of chronic myelogenous leukemia
  • Secondary AML allowed
  • No CNS leukemia

PATIENT CHARACTERISTICS:

Age

  • Over 60

Performance status

  • ECOG 0-3

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin no greater than 3 mg/dL

Renal

  • Creatinine less than 2 mg/dL

Cardiovascular

  • Ejection fraction at least 45% by MUGA or 2-dimensional echocardiogram

Other

  • No other malignancy for which patient is concurrently receiving treatment
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No other concurrent colony-stimulating factors (e.g., epoetin alfa)

Chemotherapy

  • No prior chemotherapy for AML except hydroxyurea

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00046930

  Show 92 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Larry D. Cripe, MD Indiana University Melvin and Bren Simon Cancer Center
Investigator: Brenda W. Cooper, MD Case Comprehensive Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:
Cripe LD, Li X, Litzow M, et al.: A randomized, placebo-controlled, double blind trial of the MDR modulator, zosuquidar, during conventional induction and post-remission therapy for Pts > 60 years of age with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): ECOG 3999. [Abstract] Blood 108 (11): A-423, 2006.

Study ID Numbers: CDR0000257122, ECOG-E3999
Study First Received: October 3, 2002
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00046930     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult acute monocytic leukemia (M5b)
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
 secondary acute myeloid leukemia
untreated adult acute myeloid leukemia
de novo myelodysplastic syndromes
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Daunorubicin
Antimetabolites, Antineoplastic
Immunologic Factors
Precancerous Conditions
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Anemia, Refractory
Pathologic Processes
 Syndrome
Therapeutic Uses
Anemia, Aplastic
Cytarabine
Neoplasms by Histologic Type
Disease
Hematologic Diseases
Myelodysplastic Syndromes
Anemia
Leukemia, Myeloid
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Anemia, Refractory, with Excess of Blasts

ClinicalTrials.gov processed this record on February 08, 2010



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