Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Alternate Title

Combination Chemotherapy in Treating Patients With HIV-Related Non-Hodgkin's Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI E-1494 E1494

Objectives

I.  Evaluate the complete response rate, progression-free survival, and 
survival of patients with HIV-related intermediate- and high-grade 
non-Hodgkin's lymphoma treated with CDE 
(cyclophosphamide/doxorubicin/etoposide) plus didanosine (ddI).

II.  Evaluate the event-free survival, including the incidence of death, 
progression of lymphoma, or AIDS-defining event, in these patients.

III.  Assess the toxicity of CDE plus ddI in this patient population.

Entry Criteria

Disease Characteristics:

Histologically confirmed HIV-associated non-Hodgkin's lymphoma of an
intermediate- or high-grade histology
  Pathology review of original diagnostic material required

Concurrent stable mucocutaneous Kaposi's sarcoma that has not required
systemic therapy (other than interferon) allowed
  Interferon discontinued at least 5 days prior to entry

Measurable or evaluable disease required, including:
  Clearly measurable lesions on radiograph

  Abnormalities on CT, including clearly defined abdominal masses

  Enlarged spleen and/or liver extending at least 5 cm below the costal margin
  on quiet respiration
     Lymphomatous hepatic involvement as sole disease site allowed if proven
     by biopsy

No clinical or radiologic evidence of parenchymal CNS involvement
  Meningeal lymphoma permitted

Concurrent infectious process must be ruled out or under treatment if any of
the following symptoms are present:
  Unexplained fever
  Night sweats
  Involuntary weight loss of greater than 10% of normal weight
  Diarrhea persisting for more than 2 weeks

  Symptom-specific work-up must include the following tests:
     Blood culture for Mycobacterium avium intracellulare

     Serum cryptococcal antigen

     Measure of pulmonary function (in patients with respiratory symptoms) to
     exclude Pneumocystis carinii pneumonia, including:
        Chest x-ray
        Gallium scan, resting and exercising arterial blood gas, or pulmonary
           function tests or DLCO

     Special stains for ova and parasites in patients with diarrhea

     Brain CT or MRI and lumbar puncture with evaluation for acid-fast
     bacilli, Cryptococcus, and fungus in patients with CNS symptoms

Must have received at least one commercially available protease inhibitor for
at least 1 week prior to registration

Prior/Concurrent Therapy:

Biologic therapy:
  See Disease Characteristics

Chemotherapy:
  No prior chemotherapy

Endocrine therapy:
  Concurrent corticosteroids permitted at doses no greater than the equivalent
  of 5 mg/day of prednisone

Radiotherapy:
  No prior pelvic radiotherapy
  Prior radiotherapy for mucocutaneous Kaposi's sarcoma allowed
  Concurrent localized-field irradiation (including brain irradiation)
   allowed

Surgery:
  Not specified

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0-2

Hematopoietic:
  (unless lymphomatous marrow involvement)
  ANC at least 1,000
  Platelets at least 50,000

Hepatic:
  Not specified

Renal:
  Creatinine no greater than 3.0 mg/dL

Cardiovascular:
  Normal left ventricular ejection fraction by MUGA or echocardiogram required
  if any of the following:
     History of heart disease
     Symptoms or signs of congestive heart failure
     Radiographic evidence of cardiomegaly
     EKG evidence of prior myocardial infarction

Other:
  No pancreatitis
  No grade 2 or worse peripheral neuropathy
  No prior or concurrent malignancy except:
     Kaposi's sarcoma
     Curatively treated in situ carcinoma of the cervix
     Nonmelanomatous skin cancer
  No pregnant or nursing women
  Effective contraception required of fertile patients

Expected Enrollment

55 patients will be accrued per arm for a total of 110 patients.

Outline

All patients are treated on Regimen A; those with small noncleaved cell 
lymphoma, lymphomatous bone marrow involvement, or lymphomatous meningitis 
receive concurrent CNS prophylaxis/therapy on Regimen B.

The following acronyms are used:
  ARA-C    Cytarabine, NSC-63878
  CDE      CTX/DOX/VP-16
  CF       Leucovorin calcium, NSC-3590
  CTX      Cyclophosphamide, NSC-26271
  ddI      Didanosine, NSC-612049
  DOX      Doxorubicin, NSC-123127
  G-CSF    Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629
  MTX      Methotrexate, NSC-740
  TMP-SMX  Trimethoprim-sulfamethoxazole
  VP-16    Etoposide, NSC-141540
  WBRT     Whole-Brain Radiotherapy using 4-6 MV photons (Co60 or linear
           accelerator)

Regimen A:  3-Drug Combination Systemic Chemotherapy with Hematologic Toxicity 
Attenuation plus Antiviral Therapy.  CDE; with G-CSF; plus ddI.

Regimen B:  Single-Agent Intrathecal Chemotherapy or, as indicated, 
Radiotherapy plus Alternating Single-Agent Intrathecal Chemotherapy Regimens.  
IT ARA-C; or, in patients with lymphomatous meningitis, WBRT; plus IT ARA-C; 
alternating with IT MTX/CF.

Sparano JA, Lee S, Chen MG, et al.: Phase II trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Trial (E1494). J Clin Oncol 22 (8): 1491-500, 2004.[PUBMED Abstract]

Sparano JA, Lee S, Chen MG, et al.: Phase II trial of infusional cyclophosphamide, doxorubicin, and etoposide (CDE) in HIV associated non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group trial (E1494). [Abstract] Proceedings of the American Society of Clinical Oncology 18: A41, 12a, 1999.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Joseph Sparano, MD, Protocol chair		Ph: 718-904-2555 Email: jsparano@montefiore.org