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

NCT ID: NCT00052442

Last Updated: 2021-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-08-31
• Study Completion Date: 2009-03-31

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

135 mg/m^2 Pralatrexate 1/2 weeks

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.

Group Type: EXPERIMENTAL

pralatrexate

Intervention Type: DRUG

30 mg/m^2 Pralatrexate 3/4 weeks

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.

Group Type: EXPERIMENTAL

pralatrexate

Intervention Type: DRUG

30 mg/m^2 Pralatrexate 6/7 weeks

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.

Group Type: EXPERIMENTAL

pralatrexate

Intervention Type: DRUG

45 mg/m^2 Pralatrexate 6/7 weeks

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.

Group Type: EXPERIMENTAL

pralatrexate

Intervention Type: DRUG

270 mg/m^2 Pralatrexate 2/4 weeks

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.

Group Type: EXPERIMENTAL

pralatrexate

Intervention Type: DRUG

Interventions

pralatrexate

Intervention Type: DRUG

Other Intervention Names

Folotyn; 10-Propargyl-10-Deazaaminopterin (PDX)

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Owen A. O'Connor, MD, PhD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

References

O'Connor OA, Horwitz S, Hamlin P, Portlock C, Moskowitz CH, Sarasohn D, Neylon E, Mastrella J, Hamelers R, Macgregor-Cortelli B, Patterson M, Seshan VE, Sirotnak F, Fleisher M, Mould DR, Saunders M, Zelenetz AD. Phase II-I-II study of two different doses and schedules of pralatrexate, a high-affinity substrate for the reduced folate carrier, in patients with relapsed or refractory lymphoma reveals marked activity in T-cell malignancies. J Clin Oncol. 2009 Sep 10;27(26):4357-64. doi: 10.1200/JCO.2008.20.8470. Epub 2009 Aug 3.

Reference Type: RESULT

PMID: 19652067 (View on PubMed)

Other Identifiers

MSKCC-02078

Identifier Type: -

Identifier Source: secondary_id

NCI-H02-0100

Identifier Type: -

Identifier Source: secondary_id

CDR0000258425

Identifier Type: -

Identifier Source: org_study_id