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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	VU-LYM-16 NCI-T94-0180, T94-0180

Objectives

I.  Assess the response rate, time to progression, and toxicity in patients 
treated with aminocamptothecin (9-AC) for recurrent or progressive, low-grade 
or intermediate- and high-grade non-Hodgkin's lymphoma.

II.  Evaluate the pharmacokinetics and pharmacodynamics of 9-AC, and formulate 
a dosing model.

III.  Assess the response rate and time to progression in patients treated 
with chronic, oral etoposide after progression on 9-AC.

IV.  Evaluate whether tumor topoisomerase I and II levels are altered by this 
treatment, and assess whether these levels are predictive of drug 
activity/resistance.

Entry Criteria

Disease Characteristics:

Histologically confirmed non-Hodgkin's lymphoma that has failed chemotherapy
  Pathology reviewed by Vanderbilt Dept. of Hematopathology
     Repeat biopsy strongly recommended
  No progression from indolent to aggressive histology
  Mixed histologies at initial diagnosis permitted
     Repeat biopsy required at progression or recurrence

Disease measurable
  Defect at least 2 x 2 cm on scan
  Splenomegaly at least 5 cm
  Hepatomegaly at least 5 cm
     Biopsy required if liver only site of measurable disease

Ineligible for potentially curative therapy or such therapy refused

Prior/Concurrent Therapy:

Recovery from prior therapy required

Biologic therapy:
  At least 3 weeks since immunotherapy

Chemotherapy:
  1 prior chemotherapy regimen required
     No more than 1 regimen allowed
        Modification in the regimen allowed for toxicity (e.g., mitoxantrone
        for doxorubicin)
     At least 3 weeks since chemotherapy (6 weeks for nitrosourea)
     No prior camptothecin or its derivatives
     Prior etoposide acceptable

Endocrine therapy:
  At least 2 weeks since corticosteroids

Radiotherapy:
  At least 3 weeks since radiotherapy

Surgery:
  Not specified

Patient Characteristics:

Age:
  18 and over

Performance status:
  ECOG 0-2

Hematopoietic:
  AGC at least 1,500
  Platelets at least 100,000

Hepatic:
  Bilirubin no greater than 1.5 mg/dl
  SGOT no greater than 2 x normal (5 x normal if hepatic involvement)

Renal:
  Creatinine no greater than 1.5 mg/dl

Other:
  No uncontrolled peptic ulcer
  No uncontrolled diabetes mellitus
     Fasting blood sugar no greater than 200 mg/dl
  No active infection
     More than 7 days since antibiotics
  No condition that would substantially decrease longevity
  HIV seronegative
  At least 5 years since other malignancy except surgically resectable:
     Nonmelanomatous skin cancer
     In situ cervical cancer
  No pregnant or nursing women
  Effective contraception required of fertile patients during and for 6 months
     after therapy

Blood/body fluid analyses within 14 days prior to registration
Imaging/exams for tumor measurement within 21 days prior to registration
Other screening exams within 42 days prior to registration

Expected Enrollment

30 eligible patients will be entered into each stratum over 1.5-2 years.  If 
only 1 of the first 15 patients/stratum responds to 9-AC, study of that 
stratum will cease.

Outline

All patients are treated on Regimen A; those who exhibit progressive or 
recurrent disease receive further therapy on Regimen B.

Regimen A:  Single-Agent Chemotherapy.  Aminocamptothecin, 9-AC, NSC-603071.

Regimen B:  Single-Agent Chemotherapy.  Etoposide, VP-16, NSC-141540.

Trial Contact Information

Trial Lead Organizations

Vanderbilt-Ingram Cancer Center

Russell DeVore, MD, Protocol chair(Contact information may not be current)		Ph: 615-936-1782; 800-811-8480 Email: russell.devore@mcmail.vanderbilt.edu