Intervention: Pralatrexate
Trial phase: Phase 1 | Phase 2
ATC code: L01BA05
SMILES: C#CCC(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 16
Group description: Pralatrexate 135 mg/m^2 administered as an IV infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks.
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