Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia and Diffuse Non-Hodgkin's Lymphoma

NCT ID: NCT00018954

Last Updated: 2012-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 1992-10-31
• Study Completion Date: 2002-10-31

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.

PURPOSE: Phase II trial to study the effectiveness of two treatment regimens for patients in developing countries with diffuse non-Hodgkin's lymphoma and acute lymphoblastic leukemia.

Detailed Description

OBJECTIVES:

• Provide a standard protocol for specific therapy that is relatively easy to administer and relatively inexpensive but conforms to modern treatment principles, and determine whether such therapy can be administered safely and effectively in patients with acute lymphoblastic lymphoma or diffuse non-Hodgkin's lymphoma who live in developing countries.
• Determine the rates of relapse and survival in patients treated with these protocols, and relate this data to disease subtype and clinical presentation in order to obtain a database on which to build future stratagems.

OUTLINE: This is a multicenter study.

Patients with acute lymphoblastic leukemia or lymphoblastic lymphoma with any degree of bone marrow involvement are assigned to Protocol MCP-841. Patients with mediastinal or localized lymphoblastic lymphoma (a single nodal or extranodal site) without bone marrow involvement, or other types of diffuse non-Hodgkin's lymphoma with or without bone marrow involvement are assigned to Protocol MCP-842.

Protocol MCP-841:

• First induction therapy: Patients receive daunorubicin (DNR) IV on days 8, 15, and 29; vincristine (VCR) IV on days 1, 8, 15, 22, and 29; asparaginase (ASP) intramuscularly (IM) every other day on days 2-20; oral prednisone (PRED) on days 1-28; and methotrexate (MTX) intrathecally (IT) on days 1, 8, 15, and 22. Second induction therapy: Patients receive oral mercaptopurine (MP) on days 1-7 and 15-21; cyclophosphamide (CTX) IV over 30 minutes on days 1 and 15; MTX IT as in first induction therapy; and cranial irradiation on days 4-14.
• Alternative to second induction (if a cranial irradiation facility is unavailable): Patients receive MP and CTX as in second induction therapy; cytarabine (ARA-C) IV every 12 hours on days 1, 2, 15, 16, 29, and 30; and MTX IT on days 8 and 22.

Patients with low-risk disease (WBC no greater than 10,000/mm3, age 3 to 6 years, no prominent lymphadenopathy (less than 3 cm in diameter in each nodal region), normal CSF, no mediastinal mass, no enlargement of liver or spleen, and no cranial nerve palsies) proceed directly to maintenance therapy. All other patients are considered high risk, and they repeat first induction therapy and then proceed to consolidation therapy.

• Consolidation therapy: Patients receive MP and CTX as in second induction therapy, VCR IV on days 1 and 15, and ARA-C subcutaneously (SC) every 12 hours on days 1-3 and 15-17.
• Maintenance therapy: Patients receive VCR IV on day 1; DNR IV on day 1; oral PRED on days 1-7; ASP IM on days 1, 3, 5, and 7; and oral MTX once weekly and oral MP daily on days 15-35, 43-63, and 71-91. Maintenance therapy continues for a total of 6 courses.

Protocol MCP-842:

• Patients undergo surgical resection of intra-abdominal masses, if feasible. Patients with low-risk disease (completely resected tumor or a single extra-abdominal site of involvement (other than the mediastinum), but without lymphoblastic lymphoma) are assigned to treatment group 2. All other patients, including those with lymphoblastic lymphoma without bone marrow involvement, are considered high risk and they are assigned to treatment group 1.
• Group 1 (high risk): Patients receive one course of regimen A comprising CTX IV over 15 minutes on days 1-4; VCR IV on days 1, 8, and 15; doxorubicin (DOX) IV on days 1 and 2; ARA-C IV over 3 hours every 12 hours on day 1; ARA-C IT on day 4; and MTX IT on days 8 and 12. Patients then receive one course of regimen B comprising ifosfamide IV over 30 minutes on days 1-5, etoposide IV over 1 hour and MTX IV on days 1-3, VCR IV on day 8, ARA-C IT on days 1 and 4, and MTX IT as in regimen A. Patients then receive a second course of regimen A, followed by a second course of regimen B.
• Group 2 (low risk): Patients receive one course of regimen A, followed by one course of regimen B, and then a second course of regimen A. DOX is withheld during both courses of regimen A. IT therapy is withheld during the second course of regimen A.

Patients are followed every 2 months for 1 year (Protocol MCP-841) or at 1, 2, 3, 4, 6, and 8 months (Protocol MCP-842), every 6 months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 4,000 patients will be accrued for this study.

Conditions

Leukemia; Lymphoma

Study Design

• Primary Study Purpose: TREATMENT

Interventions

asparaginase

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

ifosfamide

Intervention Type: DRUG

mercaptopurine

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed acute lymphoblastic leukemia (ALL)

• Lymphoblasts comprising more than 25% of nucleated cells on bone marrow aspirate

• Associated with an appropriate clinical syndrome
• OR
• Histologically proven newly diagnosed diffuse non-Hodgkin's lymphoma (NHL)
• Immunologic and/or cytochemical confirmation of diagnosis preferred

PATIENT CHARACTERISTICS:

Age:

• ALL:

• Under 25
• NHL:

• Not specified

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior therapy for ALL or NHL

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role: lead

Principal Investigators

Ian Trevor Magrath, MD, FRCP, FRCPath

Role: STUDY_CHAIR

National Cancer Institute (NCI)

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

National Cancer Institute of Egypt

Cairo, , Egypt

Kidwai Memorial Institute of Oncology

Bangalore, , India

Cancer Institute (W.I.A.)

Madras, , India

Tata Memorial Centre

Mumbai, , India

Countries

United States; Egypt; India

References

Gad-el-Mawla N, Hussein MH, Abdel-Hadi S, el-Taneer O, Adde M, Magrath I. Childhood non-Hodgkin's lymphoma in Egypt: preliminary results of treatment with a new ifosfamide-containing regimen. Cancer Chemother Pharmacol. 1989;24 Suppl 1:S20-3. doi: 10.1007/BF00253233.

Reference Type: RESULT

PMID: 2758567 (View on PubMed)

Other Identifiers

NCI-92-C-0030

Identifier Type: -

Identifier Source: secondary_id

NCI-T91-0259N

Identifier Type: -

Identifier Source: secondary_id

OH92-C-0030

Identifier Type: -

Identifier Source: secondary_id

CDR0000077227

Identifier Type: -

Identifier Source: org_study_id