Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI NCI-92-C-0162 NCI-T92-0039N, T92-0039

Objectives

I.  Determine the tolerable dose and toxicities, especially hematologic and 
neurologic, of cyclophosphamide/vincristine/doxorubicin/etoposide administered 
with dideoxyinosine (ddI) and granulocyte colony stimulating factor (G-CSF) to 
patients with AIDS-associated non-Hodgkin's lymphoma.

II.  Determine prospectively the efficacy of infusional chemotherapy/ddI/G-CSF 
in these patients.

III.  Determine the efficacy of CNS prophylaxis with intrathecal methotrexate 
in these patients.

IV.  Determine the effect of the regimen on markers of HIV infection and on 
immune competence.

V.  Investigate the molecular and cellular biology and cytogenetics of 
AIDS-associated non-Hodgkin's lymphoma, with special attention to the effect 
of treatment on cytokine production by lymphoma cells and circulating 
lymphocytes.

Entry Criteria

Disease Characteristics:

Biopsy-proven, intermediate- or high-grade non-Hodgkin's
lymphoma in patients with positive HIV serology

The following histologies are included:
  Small non-cleaved cell lymphoma (Burkitt's or non-Burkitt's)
  Large cell lymphoma
  Large cell immunoblastic lymphoma

Stages I-IV, preferably without prior treatment

No primary CNS lymphoma

No visceral Kaposi's sarcoma

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior cytotoxic chemotherapy for NHL
  No prior cytotoxic chemotherapy for Kaposi's sarcoma

Endocrine therapy:
  Not specified

Radiotherapy:
  Prior limited radiotherapy allowed at the discretion of the
     principal investigator
  No more than 3,000 rads to 1 previous radiation port

Surgery:
  Prior surgery allowed (patients who are NED following surgery
     are also eligible)

Other:
  Prior antiretroviral therapy is expected and allowed
     Patients with known intolerance to ddI may be entered at
     the discretion of the principal investigator and will
     receive zidovudine or other antiretroviral therapy

Patient Characteristics:

Age:
  18 and over

Performance status:
  Karnofsky greater than 50% (unless decreased performance
  status is attributable to untreated lymphoma)

Hematopoietic:
  Not specified

Hepatic:
  Not specified

Renal:
  Not specified

Other:
  No active opportunistic infection requiring chronic therapy
  No second malignancy except:
     Nonmelanomatous skin cancer
     Kaposi's sarcoma limited to the skin
  No pregnant women

Expected Enrollment

It is anticipated that 50 patients will be entered over 2 or 3 years.  Interim 
analysis is planned after entry of 14 patients.

Outline

Nonrandomized study.

Chemotherapy:  Antiretroviral Therapy plus 4-Drug Combination Chemotherapy 
with Hematologic Toxicity Attenuation.  Dideoxyinosine, ddI, NSC-612049 (or 
Zidovudine, ZDV, NSC-602670); plus Cyclophosphamide, CTX, NSC-26271; 
Vincristine, VCR, NSC-67574; Doxorubicin, DOX, NSC-123127; Etoposide, VP-16, 
NSC-141540; with Granulocyte Colony Stimulating Factor (Amgen), G-CSF, 
NSC-614629.

CNS Prophylaxis/Therapy:  Intrathecal Chemotherapy plus, as indicated, 
Radiotherapy.  Intrathecal Methotrexate, IT MTX, NSC-740; plus, as indicated, 
whole-brain irradiation (equipment unspecified) and, as appropriate, an 
involved-field boost.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Dwight Kaufman, MD, PhD, Protocol chair		Ph: 731-422-0408; 800-372-8221