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

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of 10-propargyl-10-deazaaminopterin in treating patients who have 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.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed Hodgkin's lymphoma or, using the World Health Organization (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 centimeter (cm) by conventional techniques OR
  * At least 1 cm by spiral computerized tomography (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 peripheral blood stem cells (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 Central nervous system (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)
* Aspartate aminotransferase/alanine aminotransferase (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 ECG 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 human immunodeficiency virus (HIV)-positive patients
* No other concurrent investigational or commercial agents or therapies with the intent to treat the malignancy