Clinical trial NCT00364923: Study of Pralatrexate With Vitamin B12 and Folic Acid in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral T-cell Lymphoma
Keywords: Peripheral T-cell Lymphoma
T-cell Lymphoma
Lymphoma
PDX
Pralatrexate
Vitamin B12
Folic acid
Lead sponsor: Acrotech Biopharma Inc.
Sponsor class: INDUSTRY
First posted: 2006-08-16
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Response Rate Per Independent Central Review
timeFrame: 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 outcomes:
measure: Duration of Response Per Independent Central Review
timeFrame: 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
measure: Progression-free Survival Per Independent Central Review
timeFrame: 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
measure: Overall Survival Per Independent Central Review
timeFrame: 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.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Hackensack
country: United States
facility: The Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Brussels
country: Belgium
facility: Cliniques Universitaire Saint-Luc
city: Yvoir
country: Belgium
facility: Cliniques Universitaires UCL
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Creteil
country: France
facility: CHU Henri Mondor
city: Dijon
country: France
facility: CHU DIJON - Hôpital d'enfant
city: Nice
country: France
facility: CHU Nice - Hôpital de l'Archet 1
city: Paris
country: France
facility: CHU Nantes - Hôtel Dieu
city: Paris
country: France
facility: CHU Saint Louis
city: Pierre-Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Reims
country: France
facility: CHU Robert Debré
city: Bologna
country: Italy
facility: Ospedale Sant'Orsola - Policlinico Sant'Orsola
city: London
country: United Kingdom
facility: St. Georges Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Columbia University
name: Owen O'Connor, MD, PhD
role: STUDY_CHAIR
References: