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Trial record 2 of 5 for:    CALGB 19808

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

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ClinicalTrials.gov Identifier: NCT00006363
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 4, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE October 4, 2000
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date June 4, 2013
Study Start Date  ICMJE November 2000
Actual Primary Completion Date June 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2012)
  • Disease-free survival [ Time Frame: Up to 10 years ]
    An unstratified logrank test for the induction treatment comparison and a stratified logrank test for the post-remission treatment comparison will be the primary statistical methods used for treatment comparisons.
  • Overall survival [ Time Frame: Up to 10 years ]
    An unstratified logrank test for the induction treatment comparison and a stratified logrank test for the post-remission treatment comparison will be the primary statistical methods used for treatment comparisons.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00006363 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2012)
  • Estimates of disease-free survival curves [ Time Frame: Up to 10 years ]
  • Estimates of overall survival curves [ Time Frame: Up to 10 years ]
  • Toxicities and adverse events assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) [ Time Frame: Up to 10 years ]
    Will be tabulated.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia
Official Title  ICMJE 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
Brief Summary 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. 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.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether the addition of PSC-833 (valspodar) to induction chemotherapy improves disease-free survival and overall survival for patients with acute myeloid leukemia (AML) < 60 years.

II. To determine whether post-consolidation immunotherapy with low-dose continuous/intermittent high-dose bolus subcutaneous recombinant interleukin-2 (rIL-2) (aldesleukin) improves disease-free survival and overall survival in patients with AML < 60 years in first complete remission (CR).

SECONDARY OBJECTIVES:

I. To continue to evaluate the effectiveness of three courses of high-dose ARA-C (HiDAC) (cytarabine) as curative consolidation chemotherapy in patients with core binding factor (CBF) leukemias.

II. To continue to establish the use of intensive post-remission chemotherapy with PSCT or a novel intensification sequence consisting of HiDAC/high-dose etoposide/G-CSF (filgrastim) followed by two cycles of HiDAC in patients in CR with unfavorable cytogenetics.

III. To correlate the rate of relapse and toxicity with busulfan pharmacokinetics when busulfan and etoposide are used prior to autologous stem cell transplantation for AML patients in first CR.

OUTLINE: This is a randomized, multicenter study.

INDUCTION THERAPY: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1-3. Patients with 20% or greater bone marrow cellularity and greater than 5% leukemia blasts at the end of the first course receive a second course of cytarabine IV continuously on days 1-5 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1 and 2.

ARM II: Patients receive PSC 833 IV continuously on days 1-3 and cytarabine, daunorubicin, and etoposide as in arm I. Patients with 20% or greater bone marrow cellularity and greater than 5% leukemia blasts at the end of the first course receive a second course of PSC 833 IV continuously on days 1 and 2 and cytarabine, daunorubicin, and etoposide as in arm I.

INTENSIFICATION THERAPY: Patients in complete remission receive intensification therapy. Therapy begins no earlier than 2 weeks and no later than 4 weeks after complete remission is attained. Patients are stratified according to cytogenetics (favorable [t(8;21)(q22;q22) or inv(16)(p13;q22) or t(16;16)(p13;q22)] vs unfavorable [all other karyotypes]).

FAVORABLE: Patients receive high-dose cytarabine (HiDAC) IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats no earlier than 28 days after the prior course and no later than 14 days after hematopoietic recovery for two more courses.

UNFAVORABLE: Patients are further divided into two groups based on ability to receive peripheral blood stem cell transplantation (PBSCT) (yes vs no).

PBSCT GROUP: Patients receive etoposide IV continuously and HiDAC IV over 2 hours every 12 hours on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 14 and continuing until peripheral blood stem cell (PBSC) collection is completed. Patients who are not able to undergo PBSCT after HiDAC/etoposide continue treatment in the non-PBSCT group. At least 4 weeks after HiDAC/etoposide recovery, patients receive oral busulfan every 6 hours on days -7 to -4 and etoposide IV over 4 hours on day -3 prior to PBSCT. Patients receive autologous PBSC infusion on day 0. Patients also receive G-CSF SC beginning on day 0 and continuing until hematopoietic recovery.

NON-PBSCT GROUP: Patients receive etoposide, HiDAC, and G-CSF as in the PBSCT group. After hematopoietic recovery, patients then receive HiDAC IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats no earlier than 28 days after prior course and no later than 14 days after hematopoietic recovery for one more course.

IMMUNOTHERAPY: Patients are again randomized to 1 of 2 treatment arms.

ARM I: Patients begin therapy no later than 120 days after the first day of the last course of HiDAC treatment OR day 0 of PBSCT. Patients receive low-dose interleukin-2 (IL-2) SC on days 1-14, 19-28, 33-42, 47-56, 61-70, and 75-90. In addition, patients receive high-dose IL-2 SC on days 15-17, 29-31, 43-45, 57-59, and 71-73.

ARM II: Patients are observed and receive no further therapy.

Patients are followed at 1 month, every 2 months for 2 years, every 6 months for 2 years, and then annually for 6 years.

PROJECTED ACCRUAL: A total of 720 patients will be accrued for this study within 4 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Acute Basophilic Leukemia
  • Adult Acute Eosinophilic Leukemia
  • Adult Acute Erythroid Leukemia (M6)
  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Monoblastic Leukemia (M5a)
  • Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5)
  • Adult Acute Monocytic Leukemia (M5b)
  • Adult Acute Myeloblastic Leukemia With Maturation (M2)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • 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(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Adult Acute Myelomonocytic Leukemia (M4)
  • Adult Erythroleukemia (M6a)
  • Adult Pure Erythroid Leukemia (M6b)
  • Childhood Acute Basophilic Leukemia
  • Childhood Acute Eosinophilic Leukemia
  • Childhood Acute Erythroleukemia (M6)
  • Childhood Acute Megakaryocytic Leukemia (M7)
  • Childhood Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Childhood Acute Monoblastic Leukemia (M5a)
  • Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5)
  • Childhood Acute Monocytic Leukemia (M5b)
  • Childhood Acute Myeloblastic Leukemia With Maturation (M2)
  • Childhood Acute Myeloblastic Leukemia Without Maturation (M1)
  • Childhood Acute Myelomonocytic Leukemia (M4)
  • Childhood Myelodysplastic Syndromes
  • de Novo Myelodysplastic Syndromes
  • Untreated Adult Acute Myeloid Leukemia
  • Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
Intervention  ICMJE
  • Drug: cytarabine
    Given IV
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Drug: daunorubicin hydrochloride
    Given IV
    Other Names:
    • Cerubidin
    • Cerubidine
    • daunomycin hydrochloride
    • daunorubicin
    • RP-13057
  • Drug: etoposide
    Given IV
    Other Names:
    • EPEG
    • VP-16
    • VP-16-213
  • Drug: valspodar
    Given IV
    Other Names:
    • Amdray
    • PSC 833
  • Biological: filgrastim
    Given SC
    Other Names:
    • G-CSF
    • Neupogen
  • Drug: busulfan
    Given orally
    Other Names:
    • BSF
    • BU
    • Misulfan
    • Mitosan
    • Myeloleukon
  • Procedure: autologous hematopoietic stem cell transplantation
    Undergo autologous PBSCT
  • Procedure: peripheral blood stem cell transplantation
    Undergo autologous PBSCT
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Biological: aldesleukin
    Given SC
    Other Names:
    • IL-2
    • Proleukin
    • recombinant human interleukin-2
    • recombinant interleukin-2
  • Other: clinical observation
    Undergo clinical observation
    Other Name: observation
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
Study Arms  ICMJE
  • Experimental: Induction Arm I
    Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1-3. Patients with 20% or greater bone marrow cellularity and greater than 5% leukemia blasts at the end of the first course receive a second course of cytarabine IV continuously on days 1-5 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1 and 2.
    Interventions:
    • Drug: cytarabine
    • Drug: daunorubicin hydrochloride
    • Drug: etoposide
    • Other: pharmacological study
  • Experimental: Induction Arm II
    Patients receive PSC 833 IV continuously on days 1-3 and cytarabine, daunorubicin, and etoposide as in arm I. Patients with 20% or greater bone marrow cellularity and greater than 5% leukemia blasts at the end of the first course receive a second course of PSC 833 IV continuously on days 1 and 2 and cytarabine, daunorubicin, and etoposide as in arm I.
    Interventions:
    • Drug: cytarabine
    • Drug: daunorubicin hydrochloride
    • Drug: etoposide
    • Drug: valspodar
    • Other: pharmacological study
  • Experimental: Intensification Favorable
    Patients receive HiDAC IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats no earlier than 28 days after the prior course and no later than 14 days after hematopoietic recovery for two more courses.
    Interventions:
    • Drug: cytarabine
    • Other: pharmacological study
  • Experimental: Intensification Unfavorable PBSCT Group
    Patients receive etoposide IV continuously and HiDAC IV over 2 hours every 12 hours on days 1-4. Patients also receive G-CSF SC daily beginning on day 14 and continuing until PBSC collection is completed. Patients who are not able to undergo PBSCT after HiDAC/etoposide continue treatment in the non-PBSCT group. At least 4 weeks after HiDAC/etoposide recovery, patients receive oral busulfan every 6 hours on days -7 to -4 and etoposide IV over 4 hours on day -3 prior to PBSCT. Patients receive autologous PBSC infusion on day 0. Patients also receive G-CSF SC beginning on day 0 and continuing until hematopoietic recovery.
    Interventions:
    • Drug: cytarabine
    • Drug: etoposide
    • Biological: filgrastim
    • Drug: busulfan
    • Procedure: autologous hematopoietic stem cell transplantation
    • Procedure: peripheral blood stem cell transplantation
    • Other: pharmacological study
  • Experimental: Intensification Unfavorable Non-PBSCT Group
    Patients receive etoposide, HiDAC, and G-CSF as in the PBSCT group. After hematopoietic recovery, patients then receive HiDAC IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats no earlier than 28 days after prior course and no later than 14 days after hematopoietic recovery for one more course.
    Interventions:
    • Drug: cytarabine
    • Drug: etoposide
    • Biological: filgrastim
    • Other: pharmacological study
  • Experimental: Immunotherapy Arm I
    Patients begin therapy no later than 120 days after the first day of the last course of HiDAC treatment OR day 0 of PBSCT. Patients receive low-dose IL-2 SC on days 1-14, 19-28, 33-42, 47-56, 61-70, and 75-90. In addition, patients receive high-dose IL-2 SC on days 15-17, 29-31, 43-45, 57-59, and 71-73.
    Interventions:
    • Biological: aldesleukin
    • Other: pharmacological study
  • Active Comparator: Immunotherapy Arm II
    Patients are observed and receive no further therapy.
    Interventions:
    • Other: clinical observation
    • Other: pharmacological study
Publications * Kolitz JE, George SL, Marcucci G, Vij R, Powell BL, Allen SL, DeAngelo DJ, Shea TC, Stock W, Baer MR, Hars V, Maharry K, Hoke E, Vardiman JW, Bloomfield CD, Larson RA; Cancer and Leukemia Group B. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood. 2010 Sep 2;116(9):1413-21. doi: 10.1182/blood-2009-07-229492. Epub 2010 Jun 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 11, 2012)
720
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date June 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Unequivocal histologic diagnosis of AML (> 20% blasts in the bone marrow based on the World Health Organization [WHO] and/or French-American-British Cooperative group [FAB] classifications), excluding M3 (acute promyelocytic leukemia); patients with antecedent myelodysplasia are eligible for treatment on this trial only if there was no bone marrow biopsy showing myelodysplastic syndrome (MDS) > 3 months prior to enrollment; patients with therapy-related MDS or therapy-related AML or a chronic myeloproliferative disorder are not eligible
  • No prior treatment for leukemia or myelodysplasia with four permissible exceptions:

    • Emergency leukapheresis
    • Emergency treatment for hyperleukocytosis with hydroxyurea
    • Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
    • Growth factor/cytokine support
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years to 59 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00006363
Other Study ID Numbers  ICMJE NCI-2012-02824
CALGB-19808
U10CA031946 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jonathan Kolitz Cancer and Leukemia Group B
PRS Account National Cancer Institute (NCI)
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP