Combination Chemotherapy in Treating Patients With AIDS-Related Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00002524
First received: November 1, 1999
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients with AIDS-related lymphoma.


Condition Intervention Phase
Lymphoma
Biological: Bleomycin Sulfate
Biological: Filgrastim
Drug: Cisplatin
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Doxorubicin Hydrochloride (DOX)
Drug: Etoposide
Drug: Fluorouracil
Drug: Ifosfamide
Drug: Leucovorin calcium
Drug: Methotrexate
Drug: Methylprednisolone
Drug: Pentamidine
Drug: Prednisone
Drug: Trimethoprim-Sulfamethoxazole
Drug: Vincristine Sulfate
Drug: Zidovudine (AZT)
Radiation: Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study in AIDS-Related Lymphomas

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Patients with Clinical Response [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
    Clinical Responses categorized by: Complete Response (CR), Partial Response (PR), Minor Response, Stable Disease or Progressive Disease


Enrollment: 46
Study Start Date: June 1993
Study Completion Date: October 2005
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen A
Regimen A: 5-Drug Combination Chemotherapy followed by Radiotherapy.
Biological: Bleomycin Sulfate
Other Names:
  • Blenoxane
  • BLM
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
  • Neosar
Drug: Doxorubicin Hydrochloride (DOX)
Other Names:
  • Adriamycin PFS
  • Adriamycin RDF
Drug: Pentamidine
Other Name: Pentam-300
Drug: Prednisone Drug: Trimethoprim-Sulfamethoxazole
Other Names:
  • SMX
  • Bactrim
  • Cotrim
  • Septra
  • Sulfamethoprim
  • Sulfatrim
  • Sulfoxaprim
  • Trisulfam
  • Uroplus
  • Co-trimoxazole
  • SMX-TMP
Drug: Vincristine Sulfate Drug: Zidovudine (AZT)
Other Name: Retrovir
Radiation: Radiation Therapy
Other Names:
  • RT
  • Radiotherapy
Experimental: Regimen B
Regimen B: 4-Drug Combination Chemotherapy alternating with 3-Drug Combination Chemotherapy followed, as indicated, by Radiotherapy
Biological: Filgrastim
Other Names:
  • G-CSF
  • Neupogen
Drug: Cytarabine
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytarabine arabinosine hydrochloride
Drug: Doxorubicin Hydrochloride (DOX)
Other Names:
  • Adriamycin PFS
  • Adriamycin RDF
Drug: Etoposide
Other Name: VePesid
Drug: Ifosfamide
Other Name: Ifex
Drug: Methotrexate Drug: Methylprednisolone
Other Names:
  • Depo-Medrol
  • Medrol
  • Solu-Medrol
Drug: Pentamidine
Other Name: Pentam-300
Drug: Trimethoprim-Sulfamethoxazole
Other Names:
  • SMX
  • Bactrim
  • Cotrim
  • Septra
  • Sulfamethoprim
  • Sulfatrim
  • Sulfoxaprim
  • Trisulfam
  • Uroplus
  • Co-trimoxazole
  • SMX-TMP
Drug: Zidovudine (AZT)
Other Name: Retrovir
Radiation: Radiation Therapy
Other Names:
  • RT
  • Radiotherapy
Experimental: Regimen C
Regimen C: 2-Drug Combination Chemotherapy with Drug Modulation followed, as indicated, by Radiotherapy.
Biological: Filgrastim
Other Names:
  • G-CSF
  • Neupogen
Drug: Cisplatin
Other Names:
  • Platinol
  • Plationol-AQ
  • CDDP
Drug: Fluorouracil
Other Names:
  • 5-FU
  • Adrucil
  • Efudex
  • 5-Fluorouracil
Drug: Leucovorin calcium
Other Names:
  • Citrovorum
  • Wellcovorin
Drug: Pentamidine
Other Name: Pentam-300
Drug: Trimethoprim-Sulfamethoxazole
Other Names:
  • SMX
  • Bactrim
  • Cotrim
  • Septra
  • Sulfamethoprim
  • Sulfatrim
  • Sulfoxaprim
  • Trisulfam
  • Uroplus
  • Co-trimoxazole
  • SMX-TMP
Drug: Zidovudine (AZT)
Other Name: Retrovir
Radiation: Radiation Therapy
Other Names:
  • RT
  • Radiotherapy

Detailed Description:

OBJECTIVES: I. Develop an effective chemotherapy regimen with mild immunosuppressive and myelosuppressive properties to treat patients with AIDS-related lymphoma (ARL) who have severe T4 lymphopenia. II. Estimate the CR rate, lymphoma-free survival, and overall survival of non-T4 lymphopenic patients and patients who present with nonbulky Ann Arbor stage I ARL treated with standard regimens of known effectiveness. III. Evaluate the effects on long-term outlook of concurrent antiretroviral therapy, prophylactic antibiosis with trimethoprim/sulfamethoxazole or aerosolized pentamidine, and prn use of granulocyte colony-stimulating factor for severe myelosuppression.

OUTLINE: Patients are assigned to Regimens A, B, and C according to histology and extent of disease and the degree of immunosuppression as follows: Regimen A: Patients with Ann Arbor stage I intermediate grade or immunoblastic lymphoma with measurable nonbulky disease (less than 7 cm), low LDH (less than 686), and no prior opportunistic infection irrespective of T4 count; also those with nonmeasurable stage I extranodal primaries (infiltration of less than 2/3 of an organ site, e.g., stomach, rectum, esophagus, sinus cavity) irrespective of T4 count. Regimen B: All patients (except primary brain lymphoma patients) not assigned to Regimen A who have T4 counts of at least 200 and no history of opportunistic infection; includes all stages of small noncleaved cell lymphoma and bulky stage I and stages II-IV intermediate grade and immunoblastic lymphoma. Regimen C: Patients not assigned to Regimen A or B, i.e., those with T4 counts less than 200 and/or a history of opportunistic infection and those with primary brain lymphoma. The following acronyms are used: ARA-C Cytarabine, NSC-63878 BLEO Bleomycin, NSC-125066 CDDP Cisplatin, NSC-119875 CF Leucovorin calcium, NSC-3590 CTX Cyclophosphamide, NSC-26271 DOX Doxorubicin, NSC-123127 5-FU Fluorouracil, NSC-19893 G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 IFF Ifosfamide, NSC-109723 MePRDL Methylprednisolone succinate Mesna Mercaptoethane sulfonate, NSC-113891 MTX Methotrexate, NSC-740 PRED Prednisone, NSC-10023 VCR Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540 ZDV Zidovudine, NSC-602670 Regimen A: 5-Drug Combination Chemotherapy followed by Radiotherapy. CHOP-BLEO: CTX; DOX; VCR; PRED; BLEO; followed by involved-field irradiation with megavoltage equipment. Regimen B: 4-Drug Combination Chemotherapy alternating with 3-Drug Combination Chemotherapy followed, as indicated, by Radiotherapy. ASHAP: DOX; MePRDL; ARA-C; CDDP; alternating with IMVP-16: IFF/Mesna; MTX/CF; VP-16; followed, in selected patients with initially bulky localized disease, by involved-field irradiation with megavoltage equipment. Regimen C: 2-Drug Combination Chemotherapy with Drug Modulation followed, as indicated, by Radiotherapy. FLEP: 5-FU/CF/CDDP; followed, in selected patients with initially bulky localized disease, by involved-field irradiation with megavoltage equipment. Prior to starting chemotherapy, patients with primary brain lymphoma receive a course of cranial irradiation using accelerator beams with photon energies of 6-15 MV.

PROJECTED ACCRUAL: Up to 92 patients (10 for Regimen A, 28 for Regimen B, 54 for Regimen C) will be entered over 3 years. If there are no CRs among the first 6 patients on Regimens A and B or the first 19 patients on Regimen C, accrual to that regimen will cease. If more than 4 infectious deaths occur among the first 10 patients or if the rate of disease progression exceeds 20% on any regimen, further accrual to that regimen will cease.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Previously untreated, HIV-related intermediate- and high-grade lymphoma with no previous diagnosis of Kaposi's sarcoma Pathology reviewed at M.D. Anderson Cancer Center

PATIENT CHARACTERISTICS: Age: Over 15 Performance status: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: For patients with T4 less than 200 and those with primary brain lymphoma: Creatinine no greater than 2.0 mg/dL (unless entry approved by principal investigator) Other: Serious intercurrent illness must be discussed with the principal investigator Infectious disease consultation required for complex infections Medications for other conditions allowed provided no adverse interaction with protocol therapy occurs No previously diagnosed Kaposi's sarcoma or other malignancy

PRIOR CONCURRENT THERAPY: No prior therapy for lymphoma No concurrent chemotherapy

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002524

Locations
United States, Florida
MD Anderson Cancer Center Orlando
Orlando, Florida, United States, 32806
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Peter W. McLaughlin, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00002524     History of Changes
Other Study ID Numbers: DM93-058, P30CA016672, MDA-DM-93058, NCI-T93-0088D, CDR0000078316
Study First Received: November 1, 1999
Last Updated: July 27, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS 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
Cyclophosphamide
Methotrexate
Fluorouracil
Cytarabine
Liposomal doxorubicin
Doxorubicin
Vincristine
Methylprednisolone Hemisuccinate
Prednisolone
Bleomycin
Zidovudine
Trimethoprim
Sulfamethoxazole
Trimethoprim-Sulfamethoxazole Combination
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Levoleucovorin

ClinicalTrials.gov processed this record on October 16, 2014