Comparison of Two Combination Chemotherapy Regimens in Treating Adults With Previously Untreated Leukemia or Lymphoma

January 25, 2016 updated by: Memorial Sloan Kettering Cancer Center

A Phase III Trial Comparing ARA-C/High-Dose Mitoxantrone ("ALL-2') to A Standard Vincristine/Prednisone Based Regimen ('L-20') as Induction Therapy For Adult Patients With Acute Lymphoblastic Leukemia (ALL): The ALL-4 Protocol

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective for acute lymphoblastic leukemia, lymphoblastic lymphoma, or chronic myelogenous leukemia.

PURPOSE: This randomized phase III trial is studying two different chemotherapy regimens and comparing them to see how well they work in treating adults with acute lymphoblastic leukemia, lymphoblastic lymphoma, or chronic myelogenous leukemia.

Study Overview

Detailed Description

OBJECTIVES:

  • Compare the incidence of complete remission (CR) following induction with the ALL-2 regimen (cytarabine and high-dose mitoxantrone) vs the L-20 regimen (vincristine and prednisone) in previously untreated adult patients with acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, and lymphoid blast crisis chronic myelogenous leukemia.
  • Compare the time to CR, length of hospital stay, efficacy of treatment in Philadelphia chromosome-positive ALL, and the proportion of patients achieving durable (greater than 5 years) remission in each treatment regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating institution and antecedent lymphoid blast crisis of chronic myelogenous leukemia (yes vs no). Patients are randomized to one of two treatment arms.

Arm I:

  • Patients receive induction therapy consisting of cytarabine IV over 3 hours on days 1-5 with high-dose mitoxantrone IV on day 3 and methotrexate intrathecally on days 2 and 4. Patients receive sargramostim (GM-CSF) subcutaneously or IV over 4 hours beginning on day 7 and continuing until blood counts recover.
  • At 7-14 days following induction therapy, patients receive consolidation therapy consisting of vincristine IV on days 1, 8, 15, 22, and 29, oral prednisone 2-3 times daily on days 1-30 and methotrexate intrathecally on days 8, 15, 22, and 29.
  • At 2-3 weeks following the last dose of vincristine, patients receive an additional course of consolidation therapy consisting of cyclophosphamide IV on day 1 and GM-CSF subcutaneously beginning on day 3 and continuing until blood counts recover.
  • At 3-4 weeks following the second consolidation course, patients receive a third course of consolidation therapy consisting of cytarabine IV bolus on day 1 followed by continuous infusion cytarabine on days 1-4 with etoposide IV over 1 hour on days 1-3 and methotrexate intrathecally on days 2 and 4. Patients receive GM-CSF subcutaneously beginning on day 6 and continuing until blood counts recover.
  • Following recovery from the third consolidation course, patients receive a fourth consolidation course consisting of pegaspargase IV or intramuscularly (IM) on day 1.
  • Following recovery from consolidation therapy patients receive 2 sequences of maintenance therapy with sequence one consisting of vincristine IV on days 1 and 8, oral prednisone 2-3 times daily on days 1-8, doxorubicin IV on day 15, oral mercaptopurine 2-3 times daily on days 36-64, oral methotrexate on days 39, 46, 53, and 60, dactinomycin IV on day 85, and methotrexate intrathecally on days 36 and 43.
  • At 2 weeks following sequence one of maintenance therapy, patients receive sequence two consisting of the same regimen as in the first sequence with the addition of cyclophosphamide IV and carmustine IV on day 15.
  • Patients with CNS involvement receive whole brain radiotherapy in addition to chemotherapy regimens.

Arm II:

  • Patients receive induction therapy consisting of vincristine IV on days 1, 8, 15, 22, and 29, oral prednisone 2-3 times daily on days 1-29, cyclophosphamide IV on day 5, doxorubicin IV on days 23-25 and 42, methotrexate intrathecally on days 3, 5, 13, 16, 32, and 34 and GM-CSF subcutaneously or IV over 4 hours beginning from days 7 and 27 and continuing until blood counts recover.
  • At approximately 3 weeks following induction therapy, patients receive consolidation therapy consisting of cytarabine IV bolus on day 1 followed by continuous infusion cytarabine on days 1-5, with daunorubicin IV on days 1-3 and methotrexate intrathecally on days 2 and 4. Patients receive GM-CSF subcutaneously beginning on day 7 and continuing until blood counts recover.
  • At 6-8 weeks following the first course of consolidation therapy, patients receive a second consolidation course consisting of cytarabine IV bolus on day 1 followed by continuous infusion cytarabine on days 1-4 with methotrexate IV on days 1-4 and methotrexate intrathecally on days 2 and 4. Patients receive GM-CSF subcutaneously beginning on day 6 and continuing until blood counts recover.
  • At 6-8 weeks following the second course of consolidation therapy, patients receive a third consolidation course consisting of pegaspargase IV or IM on day 1.
  • At 3-4 weeks following the third course of consolidation therapy, patients receive a fourth consolidation course consisting of cyclophosphamide IV on day 1.
  • At 3 weeks following the completion of consolidation therapy, patients receive the same maintenance regimen as in Arm I.

Treatment continues in patients achieving complete response. Patients in both arms receive alternating sequences of maintenance therapy over 2 years.

Study Type

Interventional

Enrollment (Actual)

170

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Los Angeles, California, United States, 90095-1678
        • Jonsson Comprehensive Cancer Center, UCLA
      • Stanford, California, United States, 94305-5750
        • Stanford Cancer Center at Stanford University Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute of Emory University
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • Valhalla, New York, United States, 10595
        • New York Medical College
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following malignancies:

    • Acute lymphoblastic leukemia (ALL) of B- or T-cell lineage
    • Philadelphia chromosome-positive ALL eligible
    • Lymphoblastic lymphoma
    • Chronic myelogenous leukemia in lymphoid blast crisis

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 20-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL
  • Glucocorticoids for higher bilirubin allowed prior to entry, at principal investigator's discretion

Renal:

  • Creatinine no greater than 2.0 mg/dL
  • Glucocorticoids or renal radiotherapy for higher creatinine allowed prior to entry, at principal investigator's discretion

Cardiovascular:

  • Left ventricular ejection fraction at least 50%

Other:

  • Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior biologic therapy

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • No prior endocrine therapy

Radiotherapy

  • No prior radiotherapy

Surgery

  • No prior surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Remission (CR)
Time Frame: 2 years
complete remission (CR) Disappearance of all clinical evidence of leukemia for a minimum of four weeks. The patient should have a neutrophil count > 1,000 x 10^6/1, a platelet count > 100,000 x 10^9/1, no circulating blasts, and < than or = to blasts on bone marrow differential in a qualitatively normal or hypercellular marrow. Progressive disease or failure: Increasing bone marrow infiltrate or development of organ failure or extramedullary infiltrates due to leukemia.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Nicole Lamanna, MD, Memorial Sloan Kettering Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1996

Primary Completion (Actual)

September 1, 2011

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

February 22, 2016

Last Update Submitted That Met QC Criteria

January 25, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

  • 96-015
  • P30CA008748 (U.S. NIH Grant/Contract)
  • MSKCC-96015A1
  • NCI-V96-0881

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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