Study of Pralatrexate to Treat Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Condition: Lymphoma, B-Cell
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
Intervention: Pralatrexate; Vitamin B12; Folic Acid
Intervention description: Pralatrexate injection administered as intravenous (IV) push; 1 mg intramuscular (IM) injection; Oral 1 mg tablet
Intervention MeSH terms: Vitamins; Folic Acid; Vitamin B 12; Vitamin B Complex; 10-deazaaminopterin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Relapsed; Refractory; Non-Hodgkin's

Summary:

      The purpose of this study is to determine whether pralatrexate, given with vitamin B12 and
      folic acid, is effective in the treatment of relapsed or refractory B-cell Non-Hodgkin's
      lymphoma (NHL). The study will also investigate the safety of pralatrexate with vitamin B12
      and folic acid in this participant population. Additionally, this study includes the
      collection of blood samples to investigate the pharmacokinetics (PK) of pralatrexate in this
      participant population (PK is the activity of a drug in the body over a period of time,
      including how the drug is absorbed, distributed in the body, localized in the tissues, and
      excreted from the body).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically/cytologically confirmed, measurable (lesion or node =2 cm by CT [at
             least 1 cm if by spiral CT]) B-cell Non-Hodgkin's Lymphoma, using the Revised European
             American Lymphoma (REAL) World Health Organization (WHO) disease classification

          -  Progressive or persistent disease after ≥ 1 prior treatment(s)

          -  Recovered from toxic effects of prior treatment

          -  At least 4 weeks since most recent cytotoxic therapy

          -  Easter Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Adequate blood, liver, and kidney functions as defined by laboratory levels

          -  1.0 mg/day orally of folic acid for at least 7 days prior & 1 mg intramuscular of
             vitamin B12 within 10 weeks of the planned start of pralatrexate

          -  Females of childbearing potential must agree to use medically acceptable birth control
             from start of pralatrexate 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

          -  Males who are not surgically sterile must agree to use medically acceptable birth
             control from start of pralatrexate until at least 90 days after the last
             administration of pralatrexate

          -  Available for repeat dosing and follow-up

          -  Able to give written informed consent

        Exclusion Criteria:

          -  Relapsed participants with diffuse large B-cell lymphoma (DLBCL) who are candidates
             for high-dose therapy and autologous stem cell transplantation (SCT) and for whom
             high-dose therapy and autologous SCT is a standard curative option

          -  Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of
             the cervix). If there is a history of prior malignancies other than those exceptions
             listed above, the participant must be disease-free for ≥ 5 years. Participants with
             other prior malignancies < 5 years before study entry may still be enrolled if they
             have received treatment resulting in complete resolution of the cancer and currently
             have no clinical, radiologic, or laboratory evidence of active or recurrent disease

          -  Congestive heart failure Class III/IV according to the New York Heart Association
             Functional Classification

          -  Uncontrolled hypertension

          -  Known human immunodeficiency virus (HIV)-positive diagnosis

          -  Symptomatic central nervous system (CNS) metastases or lesions for which treatment is
             required. Participants who received prophylactic CNS treatment are eligible.

          -  Participants who have undergone an allogeneic SCT

          -  Participants who have relapsed < 100 days from the time of an autologous SCT

          -  Participants with disease refractory to peripheral blood SCT or who have relapsed <
             100 days from the time of transplant

          -  Active uncontrolled infection, underlying medical condition, or other serious illness
             that would impair the ability of the participant to receive protocol treatment.

          -  Major surgery within 14 days of enrollment

          -  Receipt of any conventional chemotherapy or radiation therapy (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

          -  Receipt of systemic corticosteroids within 1 week of study treatment, unless
             participant has been taking a continuous dose of no more than 10 mg/day of prednisone
             or its equivalent 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

          -  Females who are pregnant or breastfeeding