SWOG-9320 Combination Chemotherapy, Radiation Therapy, and Antiviral Therapy in Treating Patients With AIDS-Related Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00002571
First received: November 1, 1999
Last updated: January 22, 2013
Last verified: January 2013

November 1, 1999
January 22, 2013
June 1994
November 2003   (final data collection date for primary outcome measure)
Response [ Time Frame: every 3 months while on protocol treatment ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00002571 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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SWOG-9320 Combination Chemotherapy, Radiation Therapy, and Antiviral Therapy in Treating Patients With AIDS-Related Lymphoma
Study of Promace-Cytabom With Trimethoprim Sulfamethoxazole, Zidovudine (AZT), and Granulocyte Colony Stimulating Factor (G-CSF) in Patients With AIDS-Related Lymphoma, Phase II

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Antiviral therapy may be effective treatment for AIDS-related lymphoma.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, radiation therapy, and antiviral therapy in treating patients who have AIDS-related lymphoma.

OBJECTIVES: I. Assess the response rate of AIDS-related lymphoma to ProMACE-CytaBOM (cyclophosphamide, doxorubicin, etoposide, prednisone, cytarabine, bleomycin, vincristine, methotrexate). II. Assess the toxic effects of ProMACE-CytaBOM in patients with AIDS-related lymphoma. III. Evaluate whether the incorporation of filgrastim (G-CSF) into the regimen allows treatment with full doses of the myelotoxic agents in these patients. IV. Determine whether intensive CNS treatment with intrathecal cytarabine and whole-brain irradiation prevents meningeal relapse or controls meningeal lymphomatous involvement in these patients.

OUTLINE: Patients are stratified according to participating institution and descriptive factors: histopathology (diffuse large cleaved/noncleaved and immunoblastic lymphomas vs all others), CD4 count (less than 50 vs 50 or more cells/mm3), prior opportunistic infection (yes vs no), performance status (0 and 1 vs 2), concurrent AZT (yes vs no), concurrent protease inhibitors (yes vs no), marrow involvement (yes vs no). Patients receive ProMACE-CytaBOM regimen as follows: Cyclophosphamide, doxorubicin, and etoposide IV on day 1 Cytarabine, bleomycin, vincristine, and methotrexate IV on day 8 Oral prednisone on days 1-14 Oral leucovorin calcium every 6 hours for 4 doses on day 9 Patients also receive filgrastim (G-CSF) subcutaneously on days 9-20 and oral co-trimoxazole 3 days a week throughout treatment, plus antiretroviral therapy at the discretion of the treating physician. Treatment repeats every 21 days for a maximum of 6 courses. Patients with progressive disease are removed from study after 2 courses. Remaining patients receive an additional 2 treatment courses and are then restaged. Patients without stable or progressive disease receive 2 more courses in the absence of unacceptable toxicity. Patients with positive bone marrow at study entry receive CNS prophylaxis with 5 evenly spaced doses of intrathecal cytarabine during the first 2 treatment courses and on day 1 of each subsequent course. Patients with positive CSF cytology at study entry receive intrathecal cytarabine on days 1-5 of the first treatment course and on day 1 of each subsequent course if CSF negative after 5 daily doses. Patients whose CSF remains positive after 5 days receive 5 evenly spaced doses of intrathecal methotrexate during the second treatment course. Patients with negative bone marrow and CSF cytology at study entry receive 5 evenly spaced doses of intrathecal cytarabine within 1 month of systemic therapy. All patients achieving a complete or partial response following systemic therapy and intrathecal cytarabine receive cranial irradiation to all meningeal surfaces. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over approximately 2 years.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • Biological: bleomycin sulfate
    5u/m2 IV Q21days x 6 cycles
  • Biological: filgrastim
    5ug/kg SC, Days 9-20, Q 21 days x 6 cycles
    Other Name: G-CSF
  • Drug: cyclophosphamide
    490 mg/m2 IV Q 21 days x 6 cycles
  • Drug: cytarabine
    225 mg/m2 IV Q 21 days x 6 cycles
  • Drug: doxorubicin hydrochloride
    19 mg/m2 IV Q 21 days x 6 cycles
  • Drug: etoposide
    90 mg/m2 IV Q 21 days x 6 cycles
    Other Name: VP-16
  • Drug: leucovorin calcium
    25 mg/m2 po 24 hours after methotrexate Q 6 hours x 4 doses for 6 cycles.
  • Drug: methotrexate
    90 mg/m2 IV, Q 21 days x 6 cycles.
  • Drug: prednisone
    60 mg/m2 po QD x 14days for 6 cycles
  • Drug: trimethoprim-sulfamethoxazole
    1 double throughout strength treatment tablet po on Monday, Wednesday, and Friday x 6, 21 day cycles
    Other Name: TMP/SMX
  • Drug: vincristine sulfate
    1.4 mg/m2 IV Q 21 Days x 6 cycles
  • Radiation: radiation therapy
    All patients achieving a CR or PR following systemic therapy and IT Ara-C, will receive 2,400 cGy in two hundred cGy fractions to the whole brain. Fields should adequately encompass all meningeal surfaces.
  • Drug: Intrathecal cytarabine

    If initial bone marrow positive:

    Ara-C 30 mg/m2 IT per dose x 5 doses spaced evenly during the first two cycles of therapy. Ara-C 30 mg/m2 IT Day 1 of each subsequent cycle.

    If initial CSF cytology positive:

    Ara-C 30 mg/m2 IT per dose x 5 doses spaced evenly during the first cycle of therapy. If CSF negative after above, Ara-C 30 mg/m2 IT Day 1 of each subsequent cycle. If CSF positive after initial five doses of Ara-C, IT MTX 12 mg per dose x 5 doses should be given spaced evenly during the second cycle of therapy.

    If initial bone marrow and CSF negative:

    Ara-C 30 mg/m2 IT per dose x 5 doses to be given spaced evenly within 1 month of completion of systemic therapy.

    Other Name: IT Ara-C
Experimental: ProMACE-CytaBOM + G-CSF
6 cycles of 21 days each of ProMACE-CytaBOM (cyclophosphamide 490 mg/m^2 on day 1, doxorubicin 19 mg/m^2 on day 1, etoposide 90 mg/m^2 on day 1, cytarabine 225 mg/m^2 on day 8, bleomycin 5 u/m^2 on day 8, methotrexate 90 mg/m^2 on day 8, leucovorin 25 mg/m^2 q 6 hours on days 8-9, vincristine 1.4 mg/m^2 on day 8, prednisone 60 mg/m^2 on days 1-14, allopurinol 300 mg on days 1-21 of cycle 1 and days 1-8 of cycle 2 only) plus 1 double strength tablet TMP/SMX 3 days a week plus G-CSF 5 ug/kg on days 9-20. Patients also receive intrathecal cytarabine 30 mg/m^2 (BM positive: 5 doses spaced evenly during 1st 2 cycles, then on day 1 of cycles 3-6; CSF cytology positive: 5 doses spaced evenly during 1st cycle, then on day 1 of cycles 2-6; BM and CSF negative: 5 doses spaced evenly within 1 month of completion of cycle 6). All patients with CR or PR after systemic therapy and IT cytarabine receive 2400 cGy RT to the whole brain in 12 fractions.
Interventions:
  • Biological: bleomycin sulfate
  • Biological: filgrastim
  • Drug: cyclophosphamide
  • Drug: cytarabine
  • Drug: doxorubicin hydrochloride
  • Drug: etoposide
  • Drug: leucovorin calcium
  • Drug: methotrexate
  • Drug: prednisone
  • Drug: trimethoprim-sulfamethoxazole
  • Drug: vincristine sulfate
  • Radiation: radiation therapy
  • Drug: Intrathecal cytarabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
July 2011
November 2003   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS: Histologically proven intermediate or high grade non-Hodgkin's lymphoma of one of the following histologies: Follicular, predominantly large cell Diffuse, small cleaved cell Diffuse mixed, small and large cell Diffuse, large cell (cleaved or noncleaved) Immunoblastic, large cell Small noncleaved cell, Burkitt's or non-Burkitt's No lymphoblastic lymphoma Prior diagnosis of AIDS or HIV positivity required Confirmation of HIV antibody status by Western blot mandatory Bidimensionally measurable or evaluable disease No primary CNS lymphoma Concurrent registration on protocol SWOG-8947 (central serum repository) required

PATIENT CHARACTERISTICS: Age: Over 18 Performance status: SWOG 0-2 Hematopoietic: Absolute neutrophil count at least 500/mm3 Platelet count at least 75,000/mm3 Hepatic: AST no greater than 1.5 times normal Alkaline phosphatase no greater than 1.5 times normal LDH no greater than 1.5 times normal PT/PTT normal Renal: Creatinine no greater than 2.0 times normal Creatinine clearance at least 60 mL/min Cardiovascular: No serious abnormalities on EKG No history of severe coronary artery disease No history of cardiomyopathy, congestive heart failure, or arrhythmia Other: No active uncontrolled infection No active second malignancy within 5 years except adequately treated nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy for lymphoma

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00002571
CDR0000063620, SWOG-9320, U10CA032102
No
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Study Chair: Lode J. Swinnen, MD Loyola University
Southwest Oncology Group
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP