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

Alternate Title

Chemotherapy in Young Patients With Non-Hodgkin's Lymphoma and Lymphoproliferative Disorders

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 3 months to 18 years NCI NCI-93-C-0207B NCI-T93-0006N, T93-0006

Objectives

I.  Obtain preliminary response, survival, and toxicity data in patients with 
congenital or acquired (post allograft) immunodeficiency syndromes and 
non-Hodgkin's lymphoma of small noncleaved or diffuse large cell types (or 
otherwise unclassified intermediate- or high-grade lymphoma categories) using 
multimodality treatment, including chemotherapy and cytokines and, in the case 
of HIV-infected patients, antiretroviral therapy.

II.  Obtain preliminary response, survival, and toxicity data with the same 
treatment approach in patients with lymphoproliferative syndromes secondary to 
a congenital or acquired immunodeficiency syndrome and resistant to 
noncytotoxic treatment.

III.  Characterize the cytogenetics and cellular and molecular biology of 
non-Hodgkin's lymphomas and lymphoproliferative syndromes associated with 
immunodeficiency syndromes.

IV.  Study the incidence of Epstein-Barr virus (EBV) association, the pattern 
of Epstein-Barr nucleic acid (EBNA) expression, and the EBV type in 
non-Hodgkin's lymphomas and lymphoproliferative syndromes occurring in 
patients with congenital or acquired immunodeficiency syndromes.

V.  Study the impact of chemotherapy on the course of HIV infection with 
respect to the occurrence of opportunistic and other infections and viral load.

Entry Criteria

Disease Characteristics:

Histologically proven non-Hodgkin's lymphoma associated with HIV infection or
an inherited or acquired (post allograft) immunodeficiency syndrome,
including:
  Small noncleaved cell lymphoma
  Diffuse large cell lymphoma
  Unclassified intermediate- or high-grade lymphoma

Progressive polyclonal lymphoproliferation associated with an inherited or
acquired immunodeficiency syndrome that has failed prior therapy, i.e.:
  Interferon alpha plus intravenous immunoglobulin and/or
  Interferon alpha plus retinoic acid

No low-grade or lymphoblastic lymphoma

No serious infection, including new opportunistic infection requiring therapy
  Enrollment considered once infection has been controlled provided patient is
  sufficiently stable to undergo chemotherapy

Prior/Concurrent Therapy:

See Disease Characteristics

No prior cytotoxic chemotherapy

Patient Characteristics:

Age:
  3 months to 18 years

Expected Enrollment

Up to 18 patients will be entered over 3 years.  If no more than 3 responses 
are seen in the first 8 patients treated, the trial will close.

Outline

All patients are initially treated on Regimen A; patients with both 
intracranial and systemic disease proceed to Regimen B upon completion of 
Regimen A, while those with intracranial masses alone (no systemic disease) 
receive CTX only on Regimen A (intrathecal therapy and high-dose MTX/CF are 
eliminated) and begin radiotherapy on Regimen B concomitantly.  Patients with 
testicular involvement also receive radiotherapy on Regimen C.  Patients with 
persistent disease or whose disease recurs within 1 year are then treated on 
Regimen D.  Patients who are HIV+ receive antiretroviral therapy concurrently 
with chemotherapy.

The following acronyms are used:
  ARA-C  Cytarabine, NSC-36878
  CF     Leucovorin calcium, NSC-3590
  CTX    Cyclophosphamide, NSC-26271
  ddI    Didanosine, NSC-612049
  G-CSF  Granulocyte Colony Stimulating Factor (Amgen), NSC-614629
  IFF    Ifosfamide, NSC-109724
  IVIG   Intravenous Immunoglobulin
  Mesna  Mercaptoethane sulfonate, NSC-113891
  MTX    Methotrexate, NSC-740
  ZDV    Zidovudine, NSC-602670

Regimen A:  2-Drug Systemic Chemotherapy plus Intrathecal Chemotherapy.  
CTX/Mesna; plus IT ARA-C; followed by MTX/CF; IT MTX.

Regimen B:  Radiotherapy.  Whole-brain irradiation (equipment not specified).

Regimen C:  Radiotherapy.  Testicular irradiation (equipment not specified).

Regimen D:  2-Drug Combination Chemotherapy plus Single-Agent or, as 
indicated, 2-Drug Intrathecal Chemotherapy.  IFF; ARA-C; plus IT MTX; and, in 
patients with CNS relapse, IT ARA-C.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Ian Trevor Magrath, MD, FRCP, FRCPath, Protocol chair		Ph: 301-496-1544 Email: magrathi@pb.nci.nih.gov