Tipifarnib in Treating Patients With Relapsed or Refractory Lymphoma
Condition: Anaplastic Large Cell Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, Large-Cell, Anaplastic; Lymphoma, T-Cell; Recurrence
Intervention: Laboratory Biomarker Analysis; Tipifarnib
Intervention description: Correlative studies; Given PO
Intervention MeSH terms: Tipifarnib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 93.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well tipifarnib works in treating patients with relapsed or
      refractory non-Hodgkin's lymphoma. Tipifarnib may stop the growth of cancer cells by blocking
      some of the enzymes needed for cell growth. Tipifarnib may be an effective treatment for
      non-Hodgkin's lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Biopsy-proven relapsed or refractory lymphomas; previous biopsies =< 6 months prior to
             treatment on this protocol will be acceptable as long as there has not been
             intervening therapy; if the patient has received therapy for non-Hodgkin's disease
             (NHL) between the time of the last biopsy and this protocol, then a re-biopsy is
             necessary

          -  STUDY 1: Aggressive lymphomas (permanently closed to accrual 6/28/06):

               -  Transformed lymphomas

               -  Diffuse large B cell lymphoma

               -  Mantle cell lymphoma

               -  Follicular lymphoma grade III STUDY 2: Indolent lymphomas (permanently closed to
                  accrual 9/26/07)

               -  Small lymphocytic lymphoma/chronic lymphocytic leukemia

               -  Follicular lymphoma, grades 1, 2

               -  Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
                  (MALT) type

               -  Nodal marginal zone B-cell lymphoma

               -  Splenic marginal zone B-cell lymphoma

        STUDY 3: Uncommon lymphomas:

          -  Peripheral T cell lymphoma, unspecified

          -  Anaplastic large cell lymphoma (T and null cell type)

          -  Lymphoplasmacytic lymphoma

          -  Mycosis fungoides/ Sezary syndrome

          -  Relapsed Hodgkin's disease (patients must be previously treated and either have had a
             transplant or not be eligible for a transplant)

               -  Previously treated (no limitations on the number of prior therapies); patients
                  with aggressive lymphoma (Study 1 - permanently closed to accrual 6/28/06) should
                  have received or be ineligible for potentially curable therapy including stem
                  cell transplant

               -  MEASURABLE DISEASE: Must have at least one lesion that has a single diameter of
                  >= 2 cm or tumor cells in the blood >= 5 x10^9/L

               -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

               -  Absolute neutrophil count >=1000/mm^3

               -  Platelet count >= 75,000

               -  Hemoglobin >= 9 g/dL

               -  Total bilirubin =< 2 x upper limit of normal (ULN) (if > 2 x ULN direct bilirubin
                  is required and should be =< 1.5 x ULN)

               -  Aspartate aminotransferase (AST) =< 3 x ULN (=< 5 x ULN if liver involvement is
                  present)

               -  Serum creatinine =< 2 x ULN

               -  Expected survival >= 3 months

               -  Capable of understanding the investigational nature, potential risks and benefits
                  of the study and able to provide valid informed consent

               -  Capable of swallowing intact study medication tablets

               -  Capable of following directions regarding taking study medication, or has a daily
                  caregiver who will be responsible for administering study medication

        Exclusion Criteria:

          -  Any of the following as this regimen may be harmful to a developing fetus or nursing
             child:

               -  Pregnant women

               -  Breastfeeding women

               -  Men or women of childbearing potential or their sexual partners who are unwilling
                  to employ adequate contraception (condoms, diaphragm, birth control pills,
                  injections, intrauterine device [IUD], surgical sterilization, subcutaneous
                  implants, or abstinence, etc.)

               -  NOTE: The effects of R115777 on the developing human fetus at the recommended
                  therapeutic dose are unknown

          -  Life-threatening illness (unrelated to tumor)

          -  Ongoing radiation therapy or radiation therapy =< 3 weeks prior to study registration
             unless the acute side effects associated with such therapy are resolved

          -  Therapy with myelosuppressive chemotherapy, cytotoxic chemotherapy, or biologic
             therapy =< 3 weeks (6 weeks for nitrosourea or mitomycin C) or corticosteroids =< 2
             weeks, prior to starting R11577; patients may be on corticosteroids or tapering off
             them up until the day they start R11577 as long as it is clear that they are not
             having a tumor response to the steroids or that the steroids would confuse the
             interpretation of response to R11577; patients may be receiving stable (not increased
             within the last month) chronic doses of corticosteroids with a maximum dose of 20 mg
             of prednisone per day if they are being given for disorders other than lymphoma such
             as rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency, or intractable
             symptoms of lymphoma

          -  Peripheral neuropathy >= grade 3

          -  Serious non-malignant disease such as active infection or other condition which in the
             opinion of the investigator would compromise other protocol objectives

          -  Presence of central nervous system (CNS) lymphoma

          -  Other active malignancies

          -  Once a patient begins FTI (tipifarnib) treatment, the addition of other cancer
             treatment will confound the assessment of efficacy and therefore is not allowed; this
             restriction precludes the addition of cytotoxic, immunologic agents, radiotherapy, or
             an increase in corticosteroid dose while the patient is in the treatment phase of this
             protocol

          -  Known to be human immunodeficiency virus (HIV) positive; HIV testing is not required
             but should be done if clinically indicated; HIV patients are excluded because of
             concerns regarding excess risk of complications of immunosuppressive therapy regimens

          -  Known allergy to imidazole drugs such as clotrimazole, ketoconazole, miconazole,
             econazole, fenticonazole, sulconazole, tioconazole, or terconazole