Combination Chemotherapy With or Without Valspodar in Treating Patients With Previously Untreated Acute Myeloid Leukemia

Brief Title

Combination Chemotherapy With or Without Valspodar in Treating Patients With Previously Untreated Acute Myeloid Leukemia

Official Title

Phase III Study of MDR Modulation With PSC-833 (NSC #648265) Followed by Immunotherapy With rIL-2 (NSC #373364) vs. No Further Therapy in Previously Untreated Patients With AML >60 Years

Brief Summary

      Randomized phase III trial to compare the effectiveness of combination chemotherapy with or
      without PSC 833 followed by interleukin-2 or no further therapy in treating older patients
      who have acute myeloid leukemia. Some cancers become resistant to chemotherapy drugs.
      Combining PSC 833 with more than one chemotherapy drug may reduce resistance to the drugs and
      allow the cancer cells to be killed. Combining interleukin-2 with combination chemotherapy
      plus PSC 833 may kill more cancer cells.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine whether the addition of PSC-833 to induction chemotherapy improves complete
      response rates and whether the addition of PSC-833 to induction and consolidation
      chemotherapy improves survival for patients with AML >= 60 years.

      II. To determine whether the administration of low-dose, subcutaneous rIL-2 immunotherapy
      with intermittent high-dose boluses after chemotherapy prolongs disease-free survival.

      OUTLINE: This is a partially randomized, multicenter study. Patients are stratified according
      to participating center and disease characteristics (de novo acute myeloid leukemia (AML)
      versus AML with antecedent myelodysplasia). Patients are randomized to one of two maintenance
      therapy arms.

      Arm I: Patients receive cytarabine IV continuously over 7 days and daunorubicin IV bolus
      followed by etoposide IV over 2 hours on days 1-3.

      Arm II: Patients receive treatment as in arm I with the addition of PSC 833 induction. A
      loading dose of PSC 833 IV is given over 2 hours, followed by a 74-hour continuous infusion
      of PSC 833 beginning 2 hours before daunorubicin and etoposide. Patients may receive a second
      induction course if residual leukemia is present in the bone marrow. Patients who experience
      a complete remission (CR) and meet certain other criteria receive postremission chemotherapy
      consisting of cytarabine IV continuously over 5 days plus daunorubicin IV followed by
      etoposide IV over 2 hours on days 1 and 2. Patients who are randomized to receive PSC 833
      during induction chemotherapy receive a loading dose of PSC 833 before beginning a 48-hour
      continuous infusion of PSC 833 concurrently with cytarabine/daunorubicin/etoposide
      postremission chemotherapy.

      After completing postremission chemotherapy, patients are randomized to a no further
      treatment group or interleukin-2 (IL-2) immunotherapy. Treatment begins within 5 months of
      postremission chemotherapy. IL-2 immunotherapy consists of low-dose subcutaneous (SC) IL-2 on
      days 1-14, 19-28, 33-42, 47-56, 61-70, and 75-90 and high-dose bolus SC IL-2 on days 15-17,
      29-31, 43-45, 57-59, and 71-73.

      Patients are followed every 2 months for 2 years, every 6 months for 2 years, annually until
      the tenth year, and then at relapse.
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Disease-free survival

Condition

Adult Acute Megakaryoblastic Leukemia (M7)

Intervention

cytarabine

Study Arms / Comparison Groups

 Arm I (cytarabine, daunorubicin, etoposide)

Description:  Patients receive cytarabine IV continuously over 7 days and daunorubicin IV bolus followed by etoposide IV over 2 hours on days 1-3.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

640

Start Date

January 1998

Primary Completion Date

August 2002

Eligibility Criteria

        Inclusion Criteria:

          -  Unequivocal histologic diagnosis of AML, FAB classification (M0-M7), excluding M3
             (acute promyelocytic leukemia); patients with a history of antecedent myelodysplasia
             remain eligible for treatment on this trial

          -  No prior treatment for acute leukemia or myelodysplasia with four permissible
             exceptions:

               -  Emergency leukapheresis;

               -  Emergency treatment for hyperleukocytosis with hyroxyurea;

               -  Cranial RT for CNS leukostasis (one dose only);

               -  Growth factor/cytokine support.
      

Gender

All

Ages

60 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Maria Baer, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00003190

Organization ID

NCI-2012-02793

Secondary IDs

CALGB-9720

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Maria Baer, Principal Investigator, Cancer and Leukemia Group B

Verification Date

June 2013