10-Propargyl-10-Deazaaminopterin in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma

OBJECTIVES:

- Determine the efficacy of 10-propargyl-10-deazaaminopterin, in terms of objective
response rate, duration of response, and time to disease progression, in patients with
relapsed or refractory aggressive non-Hodgkin's lymphoma or Hodgkin's lymphoma.

- Determine the impact of pharmacokinetics on toxicity and drug elimination in patients
treated with this drug.

- Determine the toxicity of this drug in these patients.

- Determine the effect of prior chemotherapy response duration on duration of response in
patients treated with this drug.

- Correlate, if possible, the pharmacodynamics (area under the curve) of this drug with
tumor response and toxicity (mucositis) in these patients.

- Correlate, if possible, intraerythrocytic folate or homocysteine levels with severity of
mucositis in patients treated with this drug.

- Determine whether levels of the RFC-1 folate transporter, folylpolyglutamate synthetase,
and folylpolyglutamate hydrolase are markers of response in patients treated with this
drug.

OUTLINE: This is an open-label study.

Patients receive 10-propargyl-10-deazaaminopterin IV over 1 hour on day 1. Courses repeat
every 14 days in the absence of disease progression or unacceptable toxicity. Patients
achieving a complete response (CR) may receive 2 additional courses beyond the CR.

PROJECTED ACCRUAL: A total of 39-72 patients (12-35 for cohort 1 and 17-37 for cohort 2) will
be accrued for this study within 10-36 months.

DISEASE CHARACTERISTICS:

- Histologically confirmed Hodgkin's lymphoma or, using the WHO classification,
aggressive non-Hodgkin's lymphoma including:

- Large B- or T-cell lymphomas (including transformed lymphomas)

- Mantle cell lymphoma

- Immunoblastic lymphoma

- At least 1 unidimensionally measurable lesion

- At least 2 cm by conventional techniques OR

- At least 1 cm by spiral CT scan

- Lymph nodes no greater than 1 cm in the short axis are considered normal

- Relapsed or refractory disease after first-line chemotherapy

- Cohort 1:

- No more than 3 prior conventional cytotoxic chemotherapy regimens

- Must have had at least a partial response (PR) lasting no more than 6 months or
refractory disease

- Patients with disease refractory to or relapsed less than 100 days from
peripheral blood stem cell (PBSC) transplantation are not eligible

- Cohort 2:

- No limit on prior treatment

- Must have had at least a PR to the last therapy lasting at least 6 months

- Patients who have received high-dose chemotherapy as part of PBSC transplantation
are eligible if relapse occurred at least 100 days after transplantation

- No clinically significant pleural effusions or ascites

- No active brain or leptomeningeal metastases

- Treated CNS disease allowed

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 70-100%

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count greater than 1,000/mm^3

- Platelet count greater than 75,000/mm^3

- Hemoglobin at least 10 g/dL

Hepatic

- Bilirubin less than 1.5 times upper limit of normal (ULN)

- AST/ALT no greater than 2.5 times ULN (4 times ULN if liver involvement)

- Alkaline phosphatase no greater than 5 times ULN

Renal

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance at least 50 mL/min

Cardiovascular

- No symptomatic congestive heart failure

- No New York Heart Association class III or IV heart disease

- No unstable angina pectoris

- No cardiac arrhythmia

- No myocardial infarction, cerebrovascular accident, or transient ischemic attack
within the past 6 months

- No history of orthostatic hypotension

- No EKG evidence of acute ischemia or significant conduction abnormality (e.g.,
bifascicular block or 2nd or 3rd degree atrioventricular blocks)

- No uncontrolled hypertension requiring active manipulation of antihypertensive
medications

- No grade III or IV edema

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No ongoing or active infection

- Febrile episodes up to 38.5° Celsius without signs of active infection allowed

- No other concurrent active cancer

- No other concurrent serious medical illness

- No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- At least 3 months since prior monoclonal antibody therapy (e.g., rituximab)

Chemotherapy

- See Disease Characterisitics

- At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or
nitrosoureas) and recovered

Endocrine therapy

- At least 7 days since prior steroids

- No concurrent steroids

Radiotherapy

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy and recovered

Surgery

- More than 4 weeks since prior major surgery

Other

- No prior antifolates

- No concurrent folic acid supplementation

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational or commercial agents or therapies with the intent
to treat the malignancy