Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Relapsed Chronic Lymphocytic Leukemia, or Relapsed B Cell Non-Hodgkin's Lymphoma
Condition: Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma
MeSH terms: Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, B-Cell; Recurrence
Intervention: Cladribine; Laboratory Biomarker Analysis; Rituximab; Vorinostat
Intervention description: Given IV; Correlative studies; Given IV; Given PO
Intervention MeSH terms: Rituximab; Antineoplastic Agents, Immunological; Vorinostat; Cladribine; 2-chloro-3'-deoxyadenosine; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving vorinostat, cladribine, and rituximab together
      works in treating patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia
      (CLL), or B cell non-Hodgkin's lymphoma (NHL) that has returned after a period of
      improvement. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy, such as cladribine, work in different
      ways to stop the growth of cancer cells, either by killing the cells, by stopping them from
      dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may
      block cancer growth in different ways by targeting certain cells. Giving vorinostat together
      with cladribine and rituximab may kill more cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be able to provide informed consent according to institutional
             guidelines

          -  Patients must have: 1) MCL; or 2) relapsed or refractory cluster of differentiation
             (CD)20 positive B-cell indolent NHL; or 3) relapsed CLL

          -  Patients must have measurable disease/disease status requirements as follows:

          -  For CLL patients, symptomatic disease as defined by the International Workshop on
             Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that mandate treatment

          -  For B-cell NHL patients must have at least one of the following to be eligible:

               -  Positron emission tomography (PET) avid or measurable disease by computed
                  tomography (CT) scan defined as at least 1 lesion that measures > 2 cm in a
                  single dimension

               -  Significant bone marrow and/or peripheral blood involvement by NHL (i.e. leukemic
                  phase) as determined by the investigator

               -  Patients with Waldenström macroglobulinemia (WM) are exempt from this requirement
                  if they have symptomatic hyperviscosity or clinically relevant cytopenias and
                  elevated serum immunoglobulin M (IgM)

          -  Patients must have adequate bone marrow reserve as indicated by an absolute neutrophil
             count (ANC) > 1.500/mm^3 and platelet count > 150.000/mm^3 if no bone marrow
             involvement; however, if there is significant lymphoma/leukemia bone marrow
             infiltration, no pre-existing hematologic parameters must be met

          -  Patients must have a performance status of 0, 1, or 2 according to Eastern Cooperative
             Oncology Group

          -  Serum creatinine < 2.0 mg/dL or estimated glomerular filtration rate (GFR) > 60 mL/min

          -  Serum bilirubin =< 1.5 × upper limit of normal (ULN)

          -  Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 × ULN

          -  Alkaline phosphatase =< 2.5 × ULN

          -  Female patients of childbearing potential must have a negative serum pregnancy test
             within 2 weeks prior to enrollment

          -  Male and female patients must agree to use an effective contraceptive method during
             the study and for a minimum of 6 months after study treatment

        Exclusion Criteria:

          -  Significant hypersensitivity to cladribine or vorinostat; hypersensitivity to
             rituximab infusion is not an exclusion criterion; however, appropriate changes to
             infusion schedules will be made based on current or prior reactions

          -  Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as
             specified in the protocol

          -  Patients with a diagnosis of a relapsed/refractory aggressive cluster of
             differentiation antigen 20 (CD20)+ B-cell neoplasm defined as Burkitt's lymphoma or
             diffuse large B-cell lymphoma

          -  A diagnosis of acute lymphoplasmic leukemia, and lymphoblastic lymphoma

          -  Use of investigational agents or any anticancer therapy within 2 weeks before study
             entry with the exception of hydroxyurea and steroids; the patient must have recovered
             from all acute toxicities from any previous therapy

          -  Have any other severe concurrent disease, or have a history of serious organ
             dysfunction or disease involving the heart, kidney, liver, or other organ system that
             may place the patient at undue risk to undergo treatment

          -  Patients with a systemic fungal, bacterial, viral, or other infection not controlled
             (defined as exhibiting ongoing signs/symptoms related to the infection and without
             improvement, despite appropriate antibiotics or other treatment)

          -  Pregnant or lactating patients

          -  Any significant concurrent disease, illness, or psychiatric disorder that would
             compromise patient safety or compliance, interfere with consent, study participation,
             follow up, or interpretation of study results

          -  Patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency
             virus (HIV) associated complex are not eligible for treatment

          -  Patients with active hepatitis B or C are not eligible for the study

          -  Patients taking other histone deacetylases (HDAC) inhibitors; for example, patients
             taking valproic acid, there must be a 14 day washout period prior to enrollment in
             this study