High Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin's Lymphoma or Central Nervous System (CNS) Lymphoma
Condition: Non-Hodgkin's Lymphoma; CNS Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Autologous stem cell transplant; High-dose chemotherapy
Intervention description: Autologous stem cell transplant following high-dose chemotherapy; High-dose chemotherapy with rituximab, thiotepa, busulfan, and cyclosphosphamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: CNS involvement

Summary:

      Current standard treatments for lymphoma involving the central nervous system include
      chemotherapy or whole brain radiation therapy (WBRT). However, many patients do not respond
      to this treatment, and some of the patients who do respond relapse after treatment.

      Previous research has shown that a stem cell transplant of a patient's own cells (autologous
      stem cell transplant) may be more effective for some patients with lymphoma involving the
      CNS. In previous research using autologous stem cell transplants for lymphoma involving the
      CNS, a conditioning regimen consisting of the drugs thiotepa, busulfan and cyclophosphamide
      (TCE) was used. These drugs have been shown to enter the nervous system.

      In this research study, the investigators are adding the drug rituximab (Rituxan) to the drug
      cytarabine for the stem cell mobilization process. Cytarabine is a standard drug for
      mobilization. In addition, rituximab will be added to the conditioning regimen of thiotepa,
      busulfan and cyclophosphamide. Rituximab is approved by the FDA for the treatment of some
      types of lymphomas, but is not approved for use in lymphomas that involve the CNS. Rituximab
      is known to be able to enter the CNS. Previous research has suggested that it may help treat
      lymphoma that involves the CNS.

      The goal of this research study is to see if adding rituximab to the stem cell mobilization
      and conditioning regimens helps treat lymphoma that involves the central nervous system.
    

Eligibility criteria:

        Inclusion Criteria:

          -  One of the following clinical criteria:secondary CNS NHL; synchronous CNS NHL;
             relapsed PCNSL; relapsed IOL; PCNSL or IOL which has only achieved a PR after adequate
             initial therapy

          -  Must have CNS or intraocular involvement by NHL

          -  Subjects with secondary CNS NHL, relapsed PCNSL, or relapsed IOL will have received
             Salvage therapy for their CNS disease

          -  Subjects with synchronous CNS NHL will have received primary therapy including
             CNS-directed therapy

          -  Must demonstrate a partial or complete response of the CNS and systemic disease to
             pre-enrollment therapy, and must be in PR or CR at the time of enrollment

          -  Age >/= 18 and </= 75 years

          -  Life expectancy >/= 3 months

          -  ECOG performance status </= 2

          -  Must have adequate organ function as defined by the protocol

        Exclusion Criteria:

          -  Stable or progressive CNS or systemic disease (SD orPD) at the time of enrollment

          -  Systemic or intrathecal chemotherapy or radiotherapy within 2 weeks prior to starting
             therapy on study

          -  Actively receiving any other study agents aimed to treat their disease

          -  A prior HDT-ASCT or allogeneic stem cell transplant (myeloablative or
             nonmyeloablative)

          -  Burkitt's lymphoma or acute lymphoblastic lymphoma

          -  A history of severe allergic reactions attributed to compounds of similar chemical or
             biologic composition to cytarabine, thiotepa, busulfan, cyclophosphamide, or rituximab

          -  Serious uncontrolled concurrent illness

          -  Any evidence of prior exposure to Hepatitis B virus

          -  HIV-positive

          -  Pregnant or lactating

          -  A history of malignancy other than NHL or PCNSL unless disease-free for at least 5
             years and are deemed by the investigator to be at low risk for recurrence of that
             malignancy. Individuals with the following cancers are eligible if diagnosed and
             treated within the past 5 years: cervical cancer in situ, and basal cell or squamous
             cell carcinoma of the skin