Combination Chemotherapy in Treating Patients With AIDS-Related Lymphoma

Pilot Study in AIDS-Related Lymphomas

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Methotrexate; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Cisplatin; Drug: Fluorouracil; Drug: Methylprednisolone; Drug: Cytarabine; Radiation: Radiation Therapy; Drug: Ifosfamide; Drug: Etoposide; Drug: Leucovorin calcium; Drug: Vincristine Sulfate; Biological: Filgrastim; Biological: Bleomycin Sulfate; Drug: Doxorubicin Hydrochloride (DOX); Drug: Pentamidine; Drug: Trimethoprim-Sulfamethoxazole; Drug: Zidovudine (AZT)

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center Orlando
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas - MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regimen A; Regimen A: 5-Drug Combination Chemotherapy followed by Radiotherapy.	Drug: Cyclophosphamide; Other Names: Cytoxan; Neosar; Drug: Prednisone; Radiation: Radiation Therapy; Other Names: Radiotherapy; RT; Drug: Vincristine Sulfate; Biological: Bleomycin Sulfate; Other Names: BLM; Blenoxane; Drug: Doxorubicin Hydrochloride (DOX); Other Names: Adriamycin PFS; Adriamycin RDF; Drug: Pentamidine; Other Names: Pentam-300; Drug: Trimethoprim-Sulfamethoxazole; Other Names: Co-trimoxazole; Bactrim; Septra; Sulfatrim; Cotrim; Sulfamethoprim; Uroplus; Trisulfam; SMX-TMP; SMX; Sulfoxaprim; Drug: Zidovudine (AZT); Other Names: Retrovir
Experimental: Regimen B; Regimen B: 4-Drug Combination Chemotherapy alternating with 3-Drug Combination Chemotherapy followed, as indicated, by Radiotherapy	Drug: Methotrexate; Drug: Methylprednisolone; Other Names: Depo-Medrol; Medrol; Solu-Medrol; Drug: Cytarabine; Other Names: Ara-C; Cytosar; DepoCyt; Cytarabine arabinosine hydrochloride; Radiation: Radiation Therapy; Other Names: Radiotherapy; RT; Drug: Ifosfamide; Other Names: Ifex; Drug: Etoposide; Other Names: VePesid; Biological: Filgrastim; Other Names: G-CSF; Neupogen; Drug: Doxorubicin Hydrochloride (DOX); Other Names: Adriamycin PFS; Adriamycin RDF; Drug: Pentamidine; Other Names: Pentam-300; Drug: Trimethoprim-Sulfamethoxazole; Other Names: Co-trimoxazole; Bactrim; Septra; Sulfatrim; Cotrim; Sulfamethoprim; Uroplus; Trisulfam; SMX-TMP; SMX; Sulfoxaprim; Drug: Zidovudine (AZT); Other Names: Retrovir
Experimental: Regimen C; Regimen C: 2-Drug Combination Chemotherapy with Drug Modulation followed, as indicated, by Radiotherapy.	Drug: Cisplatin; Other Names: CDDP; Platinol; Plationol-AQ; Drug: Fluorouracil; Other Names: 5-FU; 5-Fluorouracil; Adrucil; Efudex; Radiation: Radiation Therapy; Other Names: Radiotherapy; RT; Drug: Leucovorin calcium; Other Names: Wellcovorin; Citrovorum; Biological: Filgrastim; Other Names: G-CSF; Neupogen; Drug: Pentamidine; Other Names: Pentam-300; Drug: Trimethoprim-Sulfamethoxazole; Other Names: Co-trimoxazole; Bactrim; Septra; Sulfatrim; Cotrim; Sulfamethoprim; Uroplus; Trisulfam; SMX-TMP; SMX; Sulfoxaprim; Drug: Zidovudine (AZT); Other Names: Retrovir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients with Clinical Response	Clinical Responses categorized by: Complete Response (CR), Partial Response (PR), Minor Response, Stable Disease or Progressive Disease	3 Years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Peter W. McLaughlin, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• UT MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start: June 1, 1993
• Primary Completion (Actual): October 1, 2005
• Study Completion (Actual): October 1, 2005

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: October 4, 2004
• First Posted (Estimate): October 5, 2004

Study Record Updates

• Last Update Posted (Estimate): July 30, 2012
• Last Update Submitted That Met QC Criteria: July 27, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: 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; AIDS-related primary CNS lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, AIDS-Related; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Micronutrients; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antibiotics, Antineoplastic; Vitamins; Antifungal Agents; Reproductive Control Agents; Antiprotozoal Agents; Antiparasitic Agents; Antidotes; Vitamin B Complex; Antimalarials; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Trypanocidal Agents; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Cyclophosphamide; Etoposide; Fluorouracil; Ifosfamide; Leucovorin; Levoleucovorin; Prednisone; Zidovudine; Doxorubicin; Liposomal doxorubicin; Cytarabine; Methotrexate; Vincristine; Bleomycin; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination; Pentamidine
• Other Study ID Numbers: DM93-058; P30CA016672 (U.S. NIH Grant/Contract); MDA-DM-93058 (Other Identifier: UT MD Anderson Cancer Center); NCI-T93-0088D; CDR0000078316 (Registry Identifier: NCI PDQ)