Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

OBJECTIVES:

• Compare the effect of induction chemotherapy with or without PSC 833 (induction chemotherapy [arm II] closed to accrual as of 8/11/03) on disease-free survival and overall survival in patients with previously untreated acute myeloid leukemia.

• Determine whether post-consolidation immunotherapy with low-dose interleukin-2 (IL-2) and continuous/intermittent high-dose IL-2 improves disease-free survival and overall survival in patients who achieve first complete remission.

• Determine the effectiveness of three courses of high-dose cytarabine (HiDAC) to cure patients with core-binding factor leukemias.

• Determine the feasibility and efficacy of intensive post-remission chemotherapy using peripheral blood stem cell transplantation or a novel intensification sequence of HiDAC/high-dose etoposide/filgrastim (G-CSF) followed by two courses of HiDAC in patients with unfavorable cytogenetics in complete remission.

OUTLINE: This is a randomized, multicenter study.

• Induction Therapy:Patients are randomized to 1 of 2 treatment arms. (Arm II closed to accrual as of 8/11/03.)

• 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 (closed to accrual as of 8/11/03): 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.

Eligibility 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

Jonathan Eliahu Kolitz

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00006363
Information obtained from ClinicalTrials.gov on December 14, 2011

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