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A Phase II Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphomas and Hodgkin's Disease

Phase 2
18 Years
Not Enrolling

Thank you

Trial Information

A Phase II Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphomas and Hodgkin's Disease


- 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.

Inclusion Criteria


- 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

- No clinically significant pleural effusions or ascites

- No active brain or leptomeningeal metastases

- Treated CNS disease allowed



- 18 and over

Performance status

- Karnofsky 70-100%

Life expectancy

- Not specified


- Absolute neutrophil count greater than 1,000/mm^3

- Platelet count greater than 75,000/mm^3

- Hemoglobin at least 10 g/dL


- 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


- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance at least 50 mL/min


- 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

- No grade III or IV edema


- 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


Biologic therapy

- See Disease Characteristics

- At least 3 months since prior monoclonal antibody therapy (e.g., rituximab)


- 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


- See Disease Characteristics

- At least 4 weeks since prior radiotherapy and recovered


- More than 4 weeks since prior major surgery


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Owen A. O'Connor, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Federal Government

Study ID:




Start Date:

August 2002

Completion Date:

Related Keywords:

  • Lymphoma
  • 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
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, Non-Hodgkin



Memorial Sloan-Kettering Cancer Center New York, New York  10021