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Study of Pralatrexate and Gemcitabine With Vitamin B12 and Folic Acid in Patients With Relapsed or Refractory Lymphoproliferative Malignancies

This study is currently recruiting participants.
Verified by Allos Therapeutics, July 2008

Sponsored by: Allos Therapeutics
Information provided by: Allos Therapeutics
ClinicalTrials.gov Identifier: NCT00481871
  Purpose

This is a Phase 1/2a, non-randomized, open-label, multi-center study designed to determine the Maximum Tolerated Dose (MTD) of pralatrexate and gemcitabine when administered on sequential days with vitamin B12 and folic acid supplementation to patients with relapsed or refractory lymphoproliferative malignancies.


Condition Intervention Phase
Relapsed or Refractory Lymphoproliferative Malignancies
Drug: (RS)-10-Propargyl-10-Deazaaminopterin
Drug: Gemcitabine hydrochloride (HCl)
Phase I
Phase II

MedlinePlus related topics:   Cancer    Lymphoma   

ChemIDplus related topics:   Gemcitabine hydrochloride    Gemcitabine    Folic acid    Vitamin B 12    Hydroxocobalamin    10-Propargyl-10-deazaaminopterin   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment
Official Title:   A Phase 1/2a Open-Label Study of Sequential Pralatrexate and Gemcitabine With Vitamin B12 and Folic Acid Supplementation in Patients With Relapsed or Refractory Lymphoproliferative Malignancies

Further study details as provided by Allos Therapeutics:

Primary Outcome Measures:
  • Phase 1: MTD and recommended phase 2 dose, safety and tolerability, and PK profile. Phase 2a: tolerability and preliminary efficacy (based on investigator assessment of response) in relapsed/refractory PTCL. [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]

Estimated Enrollment:   84
Study Start Date:   May 2007
Estimated Study Completion Date:   November 2010
Estimated Primary Completion Date:   November 2010 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
A: Experimental
Pralatrexate and Gemcitabine
Drug: (RS)-10-Propargyl-10-Deazaaminopterin
One cycle of treatment will be 3 or 4 weeks in duration, depending on treatment group. The total treatment duration will not exceed 12 months from first treatment.
Drug: Gemcitabine hydrochloride (HCl)
One cycle of treatment will be 3 or 4 weeks in duration, depending on treatment group. The total treatment duration will not exceed 12 months from first treatment.
B: Experimental
Pralatrexate and Gemcitabine at MTD from Group A
Drug: (RS)-10-Propargyl-10-Deazaaminopterin
One cycle of treatment will be 3 or 4 weeks in duration, depending on treatment group. The total treatment duration will not exceed 12 months from first treatment.
Drug: Gemcitabine hydrochloride (HCl)
One cycle of treatment will be 3 or 4 weeks in duration, depending on treatment group. The total treatment duration will not exceed 12 months from first treatment.

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

Criteria

Inclusion Criteria:

  1. Phase 1: Histologically or cytologically confirmed lymphoproliferative malignancy. Patients with either Hodgkin's disease or non-Hodgkin's lymphoma using the World Health Organization (WHO) Classification are eligible, with the exception of patients with particular B-cell lymphomas, as determined in exclusion criteria #1.

    Phase 2a: Histologically/cytologically confirmed PTCL, using the Revised European American Lymphoma (REAL) WHO disease classification:

    • T/NK-cell leukemia/lymphoma
    • Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)
    • Angioimmunoblastic T-cell lymphoma
    • Blastic NK lymphoma (with skin, lymph node, or visceral involvement)
    • Anaplastic large cell lymphoma, primary systemic type
    • PTCL - unspecified
    • T/NK-cell lymphoma - nasal
    • Enteropathy-type intestinal lymphoma
    • Hepatosplenic T-cell lymphoma
    • Extranodal peripheral T/NK-cell lymphoma - unspecified
    • Subcutaneous panniculitis T-cell lymphoma
    • Transformed mycosis fungoides
  2. Documented progression of disease after at least 1 prior treatment. Any number of prior therapies will be allowed. The patient should have clearly progressed after their last prior treatment regimen. The patient has recovered from the toxic effects of prior therapy. Patients treated with a Food and Drug Administration (FDA)-approved monoclonal antibody therapy may be enrolled regardless of the time frame after the therapy if they have progression of disease.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
  4. At least 18 years of age.
  5. Adequate hematological, hepatic, and renal function as defined by:

    absolute neutrophil count (ANC) ≥ 1000/μL, platelet count ≥ 100,000/μL, total bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) (AST/ALT ≤ 5 × ULN if documented hepatic involvement with lymphoma), creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 50 mL/min.

  6. Methylmalonic acid (MMA) and homocysteine (Hcy) levels within normal limits or the patient has been on a regimen of 1 mg PO QD of folic acid for at least 10 days prior to planned start of pralatrexate and has received 1 mg IM of vitamin B12 within 10 weeks of the planned start of pralatrexate.
  7. 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 (defined as > 12 months since last menses) or are surgically sterilized do not require this test.
  8. 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.
  9. Given written informed consent (IC) and Privacy Authorization (PA).

Exclusion Criteria:

  1. Phase 1: B-cell lymphoma subtype according to the WHO classification:

    • Small B-cell lymphocytic lymphoma/B-cell chronic lymphocytic leukemia
    • Lymphoplasmacytic lymphoma (± Waldenström's macroglobulinemia)
    • Plasma cell myeloma/plasmacytoma
    • Hairy cell leukemia
    • Marginal zone B-cell lymphomas

    Phase 2a:

    • Precursor T/NK neoplasms, with the exception of blastic NK lymphoma
    • T-cell prolymphocytic leukemia (T-PLL)
    • T-cell large granular lymphocytic leukemia
    • Mycosis fungoides, other than transformed mycosis fungoides
    • Sézary syndrome
    • Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis
  2. Relapsed Hodgkin's disease or diffuse large B-cell lymphoma who are candidates for high dose therapy and autologous stem cell transplantation and for whom high dose therapy and autologous stem cell transplantation is a standard curative option.
  3. 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 ≥ 5 years.
  4. Congestive heart failure Class III/IV according to the New York Heart Association (NYHA) Functional Classification.
  5. Uncontrolled hypertension.
  6. Human immunodeficiency virus (HIV)-positive diagnosis and is receiving combination anti-retroviral therapy.
  7. Central nervous system (CNS) disease.
  8. Undergone an allogeneic stem cell transplant.
  9. Relapsed < 100 days from time of an autologous stem cell transplant. Patients with disease refractory to peripheral blood stem cell transplant (PBSCT) or who have relapsed < 100 days from the time of transplant are not eligible.
  10. 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.
  11. Major surgery within 2 weeks of planned start of treatment.
  12. Receipt of any conventional chemotherapy or radiation therapy (RT) (encompassing a substantial [>10%] amount of bone marrow) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study.
  13. Receipt of systemic 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.
  14. Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.
  15. Received a monoclonal antibody within 3 months without evidence of progression.
  16. Previous exposure to pralatrexate if it was discontinued due to treatment-related toxicity.
  17. Previous exposure to gemcitabine if it was discontinued due to treatment-related toxicity.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00481871

Contacts
Contact: Shannon Wilroy     3034266262     swilroy@allos.com    
Contact: Beth Crump     3034266262     bcrump@allos.com    

Locations
United States, California
Stanford University School of Medicine     Recruiting
      Stanford, California, United States, 94305
      Contact: Sipra Choudhury     650-736-2563     schoudhury@stanford.edu    
      Principal Investigator: Ranjana Hira Advani, MD            
United States, Nebraska
University of Nebraska Medical Center     Recruiting
      Omaha, Nebraska, United States, 68198
      Contact: Maribeth Hohenstein     402-559-9053     mahohens@unmc.edu    
      Principal Investigator: Julie Vose, MD            
United States, New York
Memorial Sloan-Kettering Cancer Center     Recruiting
      New York, New York, United States, 10021
      Contact: Hanna Weissbrot     646-227-2139     weissbrh@mskcc.org    
      Principal Investigator: Steven Horwitz, MD            
Columbia University Medical Center     Recruiting
      New York, New York, United States, 10032
      Contact: Danielle Wright     212-342-3482     dw2316@columbia.edu    
      Principal Investigator: Owen O'Connor, MD, PhD            
United States, Texas
Cancer Therapy & Research Center     Recruiting
      San Antonio, Texas, United States, 78229-4427
      Contact: Tyson DeSutter     210-450-5595     desutter@uthscsa.edu    
      Principal Investigator: Alain Mita, MD            

Sponsors and Collaborators
Allos Therapeutics

Investigators
Study Chair:     Steven M. Horwitz, MD     Memorial Sloan-Kettering Cancer Center    
  More Information

Related Info  This link exits the ClinicalTrials.gov site
 

Responsible Party:   Allos Therapeutics, Inc. ( Medical Monitor )
Study ID Numbers:   PDX-009
First Received:   June 1, 2007
Last Updated:   July 18, 2008
ClinicalTrials.gov Identifier:   NCT00481871
Health Authority:   United States: Food and Drug Administration

Keywords provided by Allos Therapeutics:
Lymphoproliferative malignancies  
Lymphoma  
Hodgkin's disease  
Non-Hodgkin's lymphoma  
PTCL  
T/NK-cell leukemia/lymphoma  
T-cell lymphoma/leukemia (HTLV 1+)  
Angioimmunoblastic T-cell lymphoma  
Blastic NK lymphoma  
Anaplastic large cell lymphoma  
T/NK-cell lymphoma  
Enteropathy-type intestinal lymphoma
Hepatosplenic T-cell lymphoma
Extranodal peripheral T/NK-cell lymphoma
Subcutaneous panniculitis T-cell lymphoma
Transformed mycosis fungoides
PDX
Pralatrexate
Gemcitabine
Gemzar
Vitamin B12
Folic acid

Study placed in the following topic categories:
Sezary syndrome
Lymphoma, Large B-Cell, Diffuse
Hodgkin's disease
Hodgkin lymphoma, adult
Cutaneous T-cell lymphoma
Hydroxocobalamin
Lymphoma, small cleaved-cell, diffuse
Aminopterin
Vitamin B 12
Sezary Syndrome
Mycosis Fungoides
Intestinal Diseases
Folic Acid
Lymphoma, large-cell
Mycoses
Leukemia
Lymphoma, T-Cell
Lymphoma, Large-Cell, Anaplastic
Anaplastic large cell lymphoma
10-deazaaminopterin
Gemcitabine
Lymphoma, Non-Hodgkin
Lymphoma
Hodgkin Disease

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Vitamin B Complex
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Hematinics
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Hematologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Radiation-Sensitizing Agents
Vitamins
Therapeutic Uses
Micronutrients

ClinicalTrials.gov processed this record on August 29, 2008




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