Study of Pralatrexate With Vitamin B12 and Folic Acid in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma

Peripheral T-cell Lymphoma Clinical Trial

— PROPEL  

Official title:

A Multi-Center, Phase 2, Open-Label Study of (RS)-10-Propargyl-10-Deazaaminopterin (Pralatrexate) With Vitamin B12 and Folic Acid Supplementation in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00364923
• Other study ID #: PDX-008
• Secondary ID: 2006-002811-29
• Status: Completed
• Phase: Phase 2
• Start date: August 2006
• Est. completion date: February 24, 2009

Study information

• Verified date: December 2019
• Source: Acrotech Biopharma LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary

• Determine the efficacy of pralatrexate with concurrent vitamin B12 and folic acid supplementation when administered to patients with relapsed or refractory peripheral T-cell lymphoma (PTCL)

Secondary

• Determine the safety of pralatrexate with concurrent vitamin B12 and folic acid supplementation when administered to patients with relapsed or refractory PTCL

• Determine the pharmacokinetic (PK) profile of pralatrexate when administered with vitamin B12 and folic acid supplementation

Description:

This is a Phase 2, single arm, non-randomized, open-label, multi-center study designed to evaluate the safety and effectiveness of pralatrexate when administered with vitamin B12 and folic acid supplementation to patients with relapsed or refractory PTCL.

Pralatrexate will be given over 3-5 minutes intravenously (IV), which means through a vein. If pralatrexate is tolerated well, the patient will receive IV injections of pralatrexate every week for 6 weeks, followed by 1 week without receiving pralatrexate. These 7 week cycles will be repeated depending on response and tolerability.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: February 24, 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically/cytologically confirmed PTCL, using the Revised European American Lymphoma (REAL) World Health Organization (WHO) disease classification:

1. T/Natural Killer (T/NK) cell leukemia/lymphoma

2. Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)

3. Angioimmunoblastic T cell lymphoma

4. Blastic Natural Killer (NK) lymphoma (with skin, lymph node, or visceral involvement)

5. Anaplastic large cell lymphoma, primary systemic type

6. PTCL - unspecified

7. T/NK-cell lymphoma - nasal

8. Enteropathy-type intestinal lymphoma

9. Hepatosplenic T cell lymphoma

10. Extranodal peripheral T/NK-cell lymphoma - unspecified

11. Subcutaneous panniculitis T-cell lymphoma

12. Transformed mycosis fungoides

• Documented progression of disease after at least 1 prior treatment. Patients may not have received experimental therapy as their only prior therapy. Patient has at least 1 biopsy from initial diagnosis or in the relapsed setting to confirm the diagnosis of PTCL. Patient has recovered from the toxic effects of prior therapy. Patients treated with monoclonal antibody therapy may be enrolled regardless of the time frame of the therapy if they have progression of disease.

• Eastern Cooperative Oncology Group (ECOG) Performance Status = 2.

• = 18 years of age.

• Adequate hematological, hepatic, and renal function.

• Women of childbearing potential must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Patients who are postmenopausal for at least 1 year or are surgically sterilized do not require this test.

• Men who are not surgically sterile must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 90 days after the last administration of pralatrexate.

• Patient has given written informed consent.

Exclusion Criteria:

• Patient has:

1. Precursor T/NK neoplasms, with the exception of blastic NK lymphoma

2. T cell prolymphocytic leukemia (T-PLL)

3. T cell large granular lymphocytic leukemia

4. Mycosis fungoides, other than transformed mycosis fungoides

5. Sézary syndrome

6. Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis

• Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease free for greater than or equal to 5 years.

• Congestive heart failure Class III/IV according to the New York Heart Association's Heart Failure Guidelines.

• Uncontrolled hypertension.

• Human immunodeficiency virus (HIV)-positive diagnosis and is receiving combination anti-retroviral therapy.

• Patient has, or history of, brain metastases or central nervous system (CNS) disease.

• Patient has undergone an allogeneic stem cell transplant.

• Patient has relapsed less than 75 days from time of an autologous stem cell transplant.

• Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness that would impair the ability of the patient to receive protocol treatment.

• Major surgery within 2 weeks of study entry.

• Receipt of any conventional chemotherapy or radiation therapy (RT) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study.

• Receipt of corticosteroids within 7 days of study treatment, unless patient has been taking a continuous dose of no more than 10 mg/day of prednisone for at least 1 month.

• Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.

• Previous exposure to pralatrexate.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-cell Lymphoma

Intervention

Drug:
• Pralatrexate Injection
Pralatrexate 30 mg/m2 via IV push over 3-5 minutes for 6 weeks in a 7 week cycle.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaire Saint-Luc	Brussels
Belgium	Cliniques Universitaires UCL	Yvoir
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
France	CHU Henri Mondor	Creteil
France	CHU DIJON - Hôpital d'enfant	Dijon
France	CHU Nice - Hôpital de l'Archet 1	Nice
France	CHU Nantes - Hôtel Dieu	Paris
France	CHU Saint Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Benite
France	CHU Robert Debré	Reims
Italy	Ospedale Sant'Orsola - Policlinico Sant'Orsola	Bologna
United Kingdom	St. Georges Hospital	London
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United States	Emory University	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago Hospital	Chicago	Illinois
United States	City of Hope National Medical Center	Duarte	California
United States	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	University of California at Los Angeles	Los Angeles	California
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Tulane Cancer Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	New York Presbyterian Hospital	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Rochester Cancer Center	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Acrotech Biopharma LLC

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate Per Independent Central Review	Patient response to treatment was determined by independent central review using International Workshop Criteria (IWC). Results present the best overall response. The initial response assessment was scheduled at week 7 (prior to Cycle 2) and then prior to every even-numbered cycle (every 14 weeks) for up to two years after first dose.	Response was assessed at 7 weeks (prior to Cycle 2) and then prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose
Secondary	Duration of Response Per Independent Central Review	Calculated only for those pts with an objective response. Pts receiving subsequent therapy (including transplant) before progressive disease (PD) was documented were censored at date of last response assessment obtained prior to subsequent therapy, with a note indicating censoring occurrence & reason. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last evaluable assessment of response. Pts who withdrew from treatment prior to PD or initiation of subsequent therapy without withdrawing consent were followed for disease status when possible.	Measured from the first day of documented response, assessed at prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose
Secondary	Progression-free Survival Per Independent Central Review	Patients (pts) with subsequent therapy prior to PD were censored at date of last response assessment prior to subsequent therapy. Pts who were alive without PD were censored at the date of last assessment of first dose. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last disease assessment or treatment day 1. Pts who withdrew consent from treatment prior to PD without withdrawing consent for follow-up were followed for disease status & survival. Pts who did not have response assessments after baseline were censored at treatment day 1.	Calculated as the number of days from treatment day 1 to the date of disease progression or death, regardless of cause for up to 2 years after initial dose
Secondary	Overall Survival Per Independent Central Review	Calculated as date of death - date of enrollment +1, estimated using the product-limit estimator. Pts who had not died (no record of death) or were lost to follow-up were censored at the date of last contact. Pts who withdrew consent to participate in the study including consent to be followed, were censored on the date of withdrawal. Pts who withdrew from treatment without withdrawing consent were followed for survival status whenever possible.	Assessed every 14 weeks while on treatment, and after disease progression no less frequently than every 6 months for up to 2 years after first dose.