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Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.

Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006363
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PSC 833 may increase the effectiveness of chemotherapy by making cancer cells more sensitive to the drugs. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy together with PSC 833 followed by a peripheral stem cell transplant with or without interleukin-2 to see how well it works compared to combination chemotherapy alone followed by a peripheral stem cell transplant with or without interleukin-2 in treating patients with acute myeloid leukemia.


Condition Intervention Phase
Leukemia
Drug: aldesleukin
Drug: busulfan
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: etoposide
Drug: filgrastim
Procedure: peripheral blood stem cell transplantation
Phase III

MedlinePlus related topics:   Cancer    Leukemia, Adult Acute    Leukemia, Adult Chronic    Leukemia, Childhood   

ChemIDplus related topics:   Filgrastim    Cytarabine    Cytarabine hydrochloride    Etoposide    Daunorubicin hydrochloride    Daunorubicin    Aldesleukin    Etoposide phosphate    Busulfan    Sdz psc 833    Interleukin-2   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Active Control
Official Title:   Phase III Randomized Study Of Induction Chemotherapy With or Without MDR-Modulation With PSC-833 (NSC #648265, IND #41121) Followed By Cytogenetic Risk-Adapted Intensification Therapy Followed By Immunotherapy With RIL-2 (NSC #373364, IND #1969) vs. Observation In Previously Untreated Patients With AML < 60 Years

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

Primary Outcome Measures:
  • Comparison of disease-free and overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:   720
Study Start Date:   November 2000

Show detailed description  Show Detailed Description

  Eligibility
Ages Eligible for Study:   15 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed acute myeloid leukemia (AML) with more than 20% blasts in bone marrow by WHO and/or FAB classifications

    • Antecedent myelodysplasia allowed if there was no bone marrow biopsy showing myelodysplastic syndromes over the previous 3 months
    • No acute promyelocytic leukemia (M3)
    • No therapy-related myelodysplastic syndromes or AML
    • No chronic myeloproliferative disorder
  • Must also be enrolled on CALGB 9665 unless inaspirable and mandatory leukemic cells cannot be obtained from the blood

PATIENT CHARACTERISTICS:

Age:

  • 15 to 59

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Not specified

Renal:

  • Not specified

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior emergency leukapheresis allowed
  • Prior growth factor/cytokine support allowed
  • No other prior biologic therapy
  • Other concurrent myeloid growth factors allowed only if prognostic factors predictive of clinical deterioration are present such as the following:

    • Pneumonia
    • Hypotension
    • Multiorgan dysfunction (sepsis syndrome)
    • Fungal infection

Chemotherapy:

  • Prior emergency treatment for hyperleukocytosis with hydroxyurea allowed
  • No other prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy:

  • No prior endocrine therapy
  • No concurrent hormonal therapy other than steroids for adrenal failure or septic shock or hormones for conditions not related to disease (e.g., insulin for diabetes or estrogens or progestins for gynecologic indications)

Radiotherapy:

  • One dose of prior cranial radiotherapy for CNS leukostasis allowed
  • No other prior radiotherapy
  • No concurrent radiotherapy

Surgery:

  • Not specified
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006363

Show 79 study locations  Show 79 Study Locations

Sponsors and Collaborators
Cancer and Leukemia Group B
National Cancer Institute (NCI)

Investigators
Study Chair:     Jonathan E. Kolitz, MD     Don Monti Comprehensive Cancer Center at North Shore University Hospital    
Investigator:     Richard A. Larson, MD     University of Chicago    
  More Information


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

Publications of Results:
Kolitz JE, Hars V, DeAngelo DJ, et al.: Phase III trial of immunotherapy with recombinant interleukin-2 (rIL-2) versus observation in patients < 60 years with acute myeloid leukemia (AML) in first remission (CR1): preliminary results from Cancer and Leukemia Group B (CALGB) 19808. [Abstract] Blood 110 (11): A-157, 2007.
 
Radmacher MD, Marcucci G, Paschka P, et al.: MicroRNA (miR) expression signatures in molecular subsets of cytogenetically normal (CN) acute myeloid leukemia (AML): a Cancer and Leukemia Group B (CALGB) study. [Abstract] J Clin Oncol 25 (Suppl 18): A-7010, 359s, 2007.
 
Kolitz JE, George SL, Marcucci G, et al.: A randomized comparison of induction therapy for untreated acute myeloid leukemia (AML) in patients < 60 years using p-glycoprotein (Pgp) modulation with valspodar (PSC833): preliminary results of Cancer and Leukemia Group B study 19808. [Abstract] Blood 106 (11): A-407, 2005.
 

Other Publications:
Langer C, Maharry K, Mrózek K, et al.: Low Meningioma 1 (MN1) gene expression to predict outcome in cytogenetically normal acute myeloid leukemia (CN-AML): A Cancer and Leukemia Group B (CALGB) study. [Abstract] J Clin Oncol 26 (Suppl 15): A-7011, 2008.
 
Langer C, Radmacher MD, Ruppert AS, Whitman SP, Paschka P, Mrozek K, Baldus CD, Vukosavljevic T, Liu CG, Ross ME, Powell BL, de la Chapelle A, Kolitz JE, Larson RA, Marcucci G, Bloomfield CD. High BAALC expression associates with other molecular prognostic markers, poor outcome and a distinct gene-expression signature in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study. Blood. 2008 Mar 31; [Epub ahead of print]
 
Paschka P, Marcucci G, Ruppert AS, Whitman SP, Mrózek K, Maharry K, Langer C, Baldus CD, Zhao W, Powell BL, Baer MR, Carroll AJ, Caligiuri MA, Kolitz JE, Larson RA, Bloomfield CD. Wilms Tumor 1 Gene Mutations Independently Predict Poor Outcome in Adults With Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study. J Clin Oncol. 2008 Jun 16; [Epub ahead of print]
 
Langer C, Ruppert, AS, Radmacher MD, et al.: High BAALC expression associates with other molecular prognostic markers, poor outcome and a distinct gene expression signature in cytogenetically normal acute myeloid leukemia (CN AML): a Cancer and Leukemia Group B (CALGB) study. [Abstract] J Clin Oncol 25 (Suppl 18): A-7013, 360s, 2007.
 
Marcucci G, Maharry K, Radmacher MD, et al.: Gene and microRNA (miRNA) expression signatures and prognostic significance of CEBPA mutations in cytogenetically normal (CN) acute myeloid leukemia (AML) with high-risk molecular features: a Cancer and Leukemia Group B (CALGB) study . [Abstract] Blood 110 (11): A-104, 2007.
 
Marcucci G, Maharry K, Whitman SP, Vukosavljevic T, Paschka P, Langer C, Mrozek K, Baldus CD, Carroll AJ, Powell BL, Kolitz JE, Larson RA, Bloomfield CD. High Expression Levels of the ETS-Related Gene, ERG, Predict Adverse Outcome and Improve Molecular Risk-Based Classification of Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study. J Clin Oncol. 2007 Jun 18; [Epub ahead of print]
 
Whitman SP, Ruppert AS, Marcucci G, Mrozek K, Paschka P, Langer C, Baldus CD, Wen J, Vukosavljevic T, Powell BL, Carroll AJ, Kolitz JE, Larson RA, Caligiuri MA, Bloomfield CD. Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study. Blood. 2007 Mar 6; [Epub ahead of print]
 
Paschka P, Marcucci G, Ruppert AS, Mrozek K, Chen H, Kittles RA, Vukosavljevic T, Perrotti D, Vardiman JW, Carroll AJ, Kolitz JE, Larson RA, Bloomfield CD; Cancer and Leukemia Group B. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol. 2006 Aug 20;24(24):3904-11.
 
Kolitz JE, George SL, Baer MR, Lee EJ, Bloomfield CD, Larson RA; Cancer and Leukemia Group B (CALGB) trials in younger and older adults. P-glycoprotein (Pgp) modulation in untreated acute myeloid leukemia (AML): Cancer and Leukemia Group B (CALGB) trials in younger and older adults. Ann Hematol. 2004;83 Suppl 1:S103-4. No abstract available.
 

Study ID Numbers:   CDR0000068234, CALGB-19808
First Received:   October 4, 2000
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00006363
Health Authority:   United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
untreated adult acute myeloid leukemia  
adult acute erythroid leukemia (M6)  
adult acute myeloblastic leukemia without maturation (M1)  
adult acute myeloblastic leukemia with maturation (M2)  
adult acute myelomonocytic leukemia (M4)  
adult acute monoblastic leukemia (M5a)  
adult acute eosinophilic leukemia  
adult acute basophilic leukemia  
adult acute megakaryoblastic leukemia (M7)
adult acute monocytic leukemia (M5b)
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)

Study placed in the following topic categories:
Leukemia, Monocytic, Acute
Daunorubicin
Acute myelogenous leukemia
Acute myelomonocytic leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Di Guglielmo's syndrome
Etoposide phosphate
Leukemia, Myelomonocytic, Acute
Leukemia
Aldesleukin
Leukemia, Erythroblastic, Acute
Interleukin-2
Busulfan
Acute erythroblastic leukemia
Acute myeloid leukemia, adult
Congenital Abnormalities
Etoposide
Acute myelocytic leukemia
Acute monoblastic leukemia
Cytarabine

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Anti-HIV Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Anti-Retroviral Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 10, 2008




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