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

Phase 1

Completed

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
135 mg/m^2 Pralatrexate 1/2 weeks	pralatrexate	Pralatrexate (PDX) 135 mg/m\^2 administered as an intravenous (IV) infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks.
30 mg/m^2 Pralatrexate 6/7 weeks	pralatrexate	PDX 30 mg/m\^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.
45 mg/m^2 Pralatrexate 6/7 weeks	pralatrexate	PDX 45 mg/m\^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.
270 mg/m^2 Pralatrexate 2/4 weeks	pralatrexate	PDX (270 mg/m\^2) administered as an IV bolus over 3-5 minutes into a side arm of a running intravenous infusion of normal saline for 2/4 weeks.
30 mg/m^2 Pralatrexate 3/4 weeks	pralatrexate	PDX 30 mg/m\^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 3/4 weeks.

Primary Outcome Measures

Name	Time	Method
Response Rate	3 weeks	Per Response Evaluation Criteria in T-cell and B-cell Lymphoma for target lesions and assessed using computerized tomography (CT) and or Positron emission tomography CT (PET CT) by local investigators: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=50% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures