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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00052442
First received: January 24, 2003
Last updated: December 3, 2013
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: pralatrexate
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphomas and Hodgkin's Disease

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: August 2002
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed Hodgkin's lymphoma or, using the 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 cm by conventional techniques OR
    • At least 1 cm by spiral 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 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 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)
  • 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 EKG 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 HIV-positive patients
  • No other concurrent investigational or commercial agents or therapies with the intent to treat the malignancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052442

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Owen A. O'Connor, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00052442     History of Changes
Other Study ID Numbers: CDR0000258425, MSKCC-02078, NCI-H02-0100
Study First Received: January 24, 2003
Last Updated: December 3, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent mantle cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent grade 3 follicular lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
10-deazaaminopterin
Aminopterin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014