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

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT00002571

Purpose

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.

Condition	Intervention	Phase
Lymphoma	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	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	STUDY OF PROMACE-CYTABOM WITH TRIMETHOPRIM SULFAMETHOXAZOLE, ZIDOVUDINE (AZT), AND GRANULOCYTE COLONY STIMULATING FACTOR (G-CSF) IN PATIENTS WITH AIDS-RELATED LYMPHOMA, PHASE II

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Leucovorin Methotrexate Acepromazine Cytarabine hydrochloride Bleomycin Doxorubicin Doxorubicin hydrochloride Etoposide Citrovorum factor Etoposide phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor Cytarabine Sulfamethoxazole Trimethoprim Leucovorin Calcium Vincristine sulfate Acepromazine maleate Folinic acid calcium salt pentahydrate Trimethoprim-sulfamethoxazole combination Bleomycin sulfate

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:

Response [ Time Frame: every 3 months while on protocol treatment ] [ Designated as safety issue: No ]

Enrollment:	52
Study Start Date:	June 1994
Study Completion Date:	July 2011
Primary Completion Date:	November 2003 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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

Arms

Assigned Interventions

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.

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

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002571

Show 85 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Lode J. Swinnen, MD

Loyola University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT00002571 History of Changes
Other Study ID Numbers:	CDR0000063620, SWOG-9320, U10CA032102
Study First Received:	November 1, 1999
Last Updated:	January 11, 2012
Health Authority:	United States: Federal Government

Keywords provided by Southwest Oncology Group:

AIDS-related peripheral/systemic lymphoma
AIDS-related diffuse large cell lymphoma
AIDS-related immunoblastic large cell lymphoma

AIDS-related small noncleaved cell lymphoma
AIDS-related diffuse mixed cell lymphoma
AIDS-related diffuse small cleaved cell lymphoma

Additional relevant MeSH terms:

Lymphoma
Lymphoma, AIDS-Related
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Bleomycin
Doxorubicin
Etoposide phosphate
Cyclophosphamide
Cytarabine

Etoposide
Methotrexate
Prednisone
Vincristine
Lenograstim
Sulfamethoxazole
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Leucovorin
Levoleucovorin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on February 09, 2012