- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00002766
Comparison of Two Combination Chemotherapy Regimens in Treating Adults With Previously Untreated Leukemia or Lymphoma
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
Status
Intervention / Treatment
- Drug: cyclophosphamide
- Radiation: radiation therapy
- Drug: mitoxantrone hydrochloride
- Drug: prednisone
- Drug: cytarabine
- Drug: daunorubicin hydrochloride
- Drug: etoposide
- Drug: methotrexate
- Drug: vincristine sulfate
- Drug: mercaptopurine
- Drug: doxorubicin hydrochloride
- Biological: sargramostim
- Drug: carmustine
- Biological: dactinomycin
- Drug: pegaspargase
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
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
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
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ARA-C/High-Dose Mitoxantrone("All-2")
See detail description
|
|
Active Comparator: Standard Vincristine/Prednisone ("L-20")
See detail description
|
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
Collaborators
Investigators
- Study Chair: Nicole Lamanna, MD, Memorial Sloan Kettering Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- B-cell adult acute lymphoblastic leukemia
- blastic phase chronic myelogenous leukemia
- chronic myelogenous leukemia, BCR-ABL1 positive
- stage III adult lymphoblastic lymphoma
- stage IV adult lymphoblastic lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- untreated adult acute lymphoblastic leukemia
- contiguous stage II adult lymphoblastic lymphoma
- stage I adult lymphoblastic lymphoma
- T-cell adult acute lymphoblastic leukemia
- stage II adult lymphoblastic lymphoma
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, Lymphoid
- Lymphoma
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Anti-Bacterial Agents
- Protein Synthesis Inhibitors
- Antibiotics, Antineoplastic
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Cyclophosphamide
- Etoposide
- Prednisone
- Doxorubicin
- Liposomal doxorubicin
- Cytarabine
- Methotrexate
- Vincristine
- Daunorubicin
- Mitoxantrone
- Mercaptopurine
- Carmustine
- Sargramostim
- Pegaspargase
- Dactinomycin
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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