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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00002766

Recruitment Status : Completed

First Posted : January 27, 2003

Results First Posted : February 22, 2016

Last Update Posted : February 22, 2016

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Memorial Sloan Kettering Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia Lymphoma	Biological: dactinomycin Biological: sargramostim Drug: carmustine Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: doxorubicin hydrochloride Drug: etoposide Drug: mercaptopurine Drug: methotrexate Drug: mitoxantrone hydrochloride Drug: pegaspargase Drug: prednisone Drug: vincristine sulfate Radiation: radiation therapy	Phase 3

Show detailed description

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 Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	170 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	March 1996
Actual Primary Completion Date :	September 2011
Actual Study Completion Date :	September 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia Lymphoma

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Lymphosarcoma Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Chronic Myeloid Leukemia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: ARA-C/High-Dose Mitoxantrone("All-2") See detail description	Biological: dactinomycin Biological: sargramostim Drug: carmustine Drug: cyclophosphamide Drug: cytarabine Drug: doxorubicin hydrochloride Drug: etoposide Drug: mercaptopurine Drug: methotrexate Drug: mitoxantrone hydrochloride Drug: pegaspargase Drug: prednisone Drug: vincristine sulfate Radiation: radiation therapy
Active Comparator: Standard Vincristine/Prednisone ("L-20") See detail description	Biological: sargramostim Drug: carmustine Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: doxorubicin hydrochloride Drug: methotrexate Drug: pegaspargase Drug: prednisone Drug: vincristine sulfate

Outcome Measures

Primary Outcome Measures :

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.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 120 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002766

Locations

Layout table for location information

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

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Layout table for investigator information

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

More Information

Layout table for additonal information

Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00002766
Other Study ID Numbers:	96-015 P30CA008748 ( U.S. NIH Grant/Contract ) MSKCC-96015A1 NCI-V96-0881
First Posted:	January 27, 2003 Key Record Dates
Results First Posted:	February 22, 2016
Last Update Posted:	February 22, 2016
Last Verified:	January 2016

Keywords provided by Memorial Sloan Kettering Cancer Center:


blastic phase chronic myelogenous leukemia untreated adult acute lymphoblastic leukemia chronic myelogenous leukemia, BCR-ABL1 positive T-cell adult acute lymphoblastic leukemia B-cell adult acute lymphoblastic leukemia stage I adult lymphoblastic lymphoma	stage II adult lymphoblastic lymphoma stage III adult lymphoblastic lymphoma stage IV adult lymphoblastic lymphoma contiguous stage II adult lymphoblastic lymphoma noncontiguous stage II adult lymphoblastic lymphoma

Additional relevant MeSH terms:

Layout table for MeSH terms

Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, Lymphoid Cytarabine Dactinomycin Prednisone Cyclophosphamide Carmustine	Doxorubicin Liposomal doxorubicin Methotrexate Etoposide Vincristine Daunorubicin Mercaptopurine Mitoxantrone Pegaspargase Sargramostim Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating

To Top