10-Propargyl-10-Deazaaminopterin in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma
Status and phase
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Study type
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Details and patient eligibility
About
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.
Full description
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.
Enrollment
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Volunteers
Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
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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
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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
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Relapsed or refractory disease after first-line chemotherapy
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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
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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
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No clinically significant pleural effusions or ascites
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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
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception
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No ongoing or active infection
- Febrile episodes up to 38.5° Celsius without signs of active infection allowed
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No other concurrent active cancer
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No other concurrent serious medical illness
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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
Trial design
Primary purpose
Allocation
Interventional model
Masking
72 participants in 5 patient groups
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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