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

NCT ID: NCT00002766

Last Updated: 2016-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-03-31
• Study Completion Date: 2011-09-30

Brief Summary

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.

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.

Conditions

Leukemia; Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARA-C/High-Dose Mitoxantrone("All-2")

See detail description

Group Type: EXPERIMENTAL

dactinomycin

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

mercaptopurine

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

pegaspargase

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Standard Vincristine/Prednisone ("L-20")

See detail description

Group Type: ACTIVE_COMPARATOR

sargramostim

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

pegaspargase

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

Interventions

dactinomycin

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

mercaptopurine

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

pegaspargase

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicole Lamanna, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Stanford Cancer Center at Stanford University Medical Center

Stanford, California, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

New York Medical College

Valhalla, New York, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MSKCC-96015A1

Identifier Type: -

Identifier Source: secondary_id

NCI-V96-0881

Identifier Type: -

Identifier Source: secondary_id

96-015

Identifier Type: -

Identifier Source: org_study_id