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

Alternate Title

Zidovudine Plus Interferon Alfa in Patients With Adult T-cell Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed over 18 NCI NCI-94-C-0070F NCI-T93-0149N, T93-0149

Objectives

I.  Estimate the therapeutic efficacy and response rates produced by 
zidovudine/interferon alfa in patients with HTLV-I-associated adult T-cell 
leukemia/lymphoma (ATL).

II.  Determine the toxic effects associated with this combination in 
HTLV-I-associated ATL.

III.  Assess the clonality of circulating leukemic cells by molecular analysis 
of the T-cell-receptor gene rearrangements and the HTLV-I integration into 
cellular DNA.

Entry Criteria

Disease Characteristics:

Histologically or cytologically confirmed adult T-cell leukemia/lymphoma (ATL)
of any stage
  No smoldering ATL, defined as:
     5% or more abnormal lymphocytes with a lymphocyte count less than 4,000
     Absence of hypercalcemia
     LDH less than 1.5 times normal
     Absence of lymphadenopathy or organ involvement other than skin or
        pulmonary lesions

HTLV-I infection, confirmed by circulating anti-HTLV-I antibodies demonstrated
by either:
  ELISA confirmed by Western blot

  Southern blot using an HTLV-I probe applied to DNA from peripheral blood
  mononuclear cells

No symptomatic CNS involvement
  Asymptomatic patients with malignant cells in the cerebrospinal fluid are
  eligible and may receive intrathecal or intraventricular therapy on study

Measurable disease required

No primary CNS lymphoma

Prior/Concurrent Therapy:

Any number of prior therapies allowed

Previously untreated patients eligible

Biologic therapy:
  No prior interferon alfa

Chemotherapy:
  More than 3 weeks since cytotoxic chemotherapy

Endocrine therapy:
  Not specified

Radiotherapy:
  More than 3 weeks since radiotherapy

Surgery:
  Not specified

Other:
  No prior zidovudine

Patient Characteristics:

Age:
  Over 18

Performance status:
  Not specified

Life expectancy:
  At least 1 month

Hematopoietic:
  Absolute granulocyte count at least 1,000/mm3

Hepatic:
  (unless abnormality is due to tumor)
  Bilirubin less than 2.0 mg/dL
  AST less than 3 times normal

Renal:
  (unless abnormality is due to tumor)
  Creatinine less than 2.0 mg/dL

Cardiovascular:
  No cardiopathies, e.g.:
     No myocardial infarction
     No angina pectoris
     No congestive heart failure
     No atrial flutter or fibrillation
     No premature ventricular contractions greater than grade 1
     No prior antiarrhythmic therapy

Other:
  No HIV antibody
  No uncontrolled medical condition that precludes treatment
  No active second cancer except:
     Squamous cell skin cancer
     Carcinoma in situ of the cervix
  Not pregnant
     Negative pregnancy test required of fertile women

Expected Enrollment

Up to 30 patients will be studied.  If no partial or complete response is 
observed in the first 9 patients, the study will close.

Outline

The following acronyms are used:
  ARA-C         Cytarabine, NSC-63878
  IFN-A         Interferon alfa (Schering), NSC-377523
  MTX           Methotrexate, NSC-750
  ZDV           Zidovudine, NSC-602670

Single-Agent Antiviral Therapy plus Biological Response Modifier Therapy plus 
(as indicated) 2-Drug Combination Intrathecal or Intraventricular 
Chemotherapy.  ZDV; plus (in patients with non-symptomatic CSF involvement) 
IFN-A; plus IT or intraventricular ARA-C/MTX.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Thomas Waldmann, MD, Protocol chair		Ph: 301-496-6656 Email: tawald@helix.nih.gov