LymphomaPhase 1/2NCT00052442
10-Propargyl-10-Deazaaminopterin in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma
A Phase 1/2 study testing pralatrexate in people with Lymphoma, run by Spectrum Pharmaceuticals, Inc at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- pralatrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2002to Mar 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- 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
- 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
- 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 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
About this study
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
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.
Read the 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
- Being tested
- pralatrexate
- Keywords
- 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
- Medical subject headings
- Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Burkitt Lymphoma, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Mantle-Cell, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pralatrexateDrug
Also called Folotyn, 10-Propargyl-10-Deazaaminopterin (PDX)
| Study group | Role | What they receive |
|---|---|---|
| 135 mg/m^2 Pralatrexate 1/2 weeks | Experimental | 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. Receives: Drug: pralatrexate |
| 30 mg/m^2 Pralatrexate 3/4 weeks | Experimental | 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. Receives: Drug: pralatrexate |
| 30 mg/m^2 Pralatrexate 6/7 weeks | Experimental | 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. Receives: Drug: pralatrexate |
| 45 mg/m^2 Pralatrexate 6/7 weeks | Experimental | 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. Receives: Drug: pralatrexate |
| 270 mg/m^2 Pralatrexate 2/4 weeks | Experimental | 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. Receives: Drug: pralatrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
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.
Measured: 3 weeks
Secondary outcomes (1)
Toxicities of Pralatrexate
Adverse events; number of patients with at least one adverse events reported.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startAug 2002
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spectrum Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Owen A. O'Connor, MD, PhD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00052442
- Sponsor's protocol ID
- CDR0000258425
- Other IDs
- MSKCC-02078, NCI-H02-0100
- Status last verified
- Aug 2021
- First submitted
- 24 Jan 2003
- Last updated
- 25 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 19652067
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00052442
- Acronym / sponsor ID
- CDR0000258425
- Conditions
- Lymphoma
- Keywords
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Spectrum Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI), Memorial Sloan Kettering Cancer Center
- Study start
- Aug 2002
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 25 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 135 mg/m^2 Pralatrexate 1/2 weeks | Experimental | Drug: pralatrexatePralatrexate (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 3/4 weeks | Experimental | Drug: pralatrexatePDX 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. |
| 30 mg/m^2 Pralatrexate 6/7 weeks | Experimental | Drug: pralatrexatePDX 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 | Experimental | Drug: pralatrexatePDX 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 | Experimental | Drug: pralatrexatePDX (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pralatrexateAlso: Folotyn, 10-Propargyl-10-Deazaaminopterin (PDX) | Drug | 135 mg/m^2 Pralatrexate 1/2 weeks, 270 mg/m^2 Pralatrexate 2/4 weeks, 30 mg/m^2 Pralatrexate 3/4 weeks, 30 mg/m^2 Pralatrexate 6/7 weeks, 45 mg/m^2 Pralatrexate 6/7 weeks |
Primary outcome
Response Rate
Time frame: 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.
1 secondary outcome
Toxicities of Pralatrexate
Time frame: 3 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19652067O'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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Owen A. O'Connor, MD, PhD study chair
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing pralatrexate in people with Lymphoma, run by Spectrum Pharmaceuticals, Inc at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00052442, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021.