Obatoclax Mesylate, Rituximab, and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

Inclusion Criteria:

• Histologically confirmed indolent B-cell non-Hodgkin lymphoma (NHL), including any of the following subtypes recognized by WHO classification:

  • Marginal zone lymphoma
  • Lymphoplasmacytic lymphoma
  • Follicular lymphoma
  • Mantle cell lymphoma
• Transformed lymphoma from a low-grade, indolent NHL allowed provided patient has received ≥ 1 prior therapy for indolent disease
• Must have received ≥ 1 prior therapy

• Relapsed disease after autologous or allogeneic stem cell transplantation (SCT) allowed (phase I)

  • No relapse after allogeneic SCT (phase II)
• No known CNS lymphoma
• ECOG performance status 0-2
• ANC ≥ 1,000/µL
• Platelet count ≥ 50,000/µL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception prior to and for the duration of study participation

• No active hepatitis B infection

  • Patients with a history of hepatitis B (surface antigen or core antibody positive) must take lamivudine or equivalent during study therapy
• No history of documented human anti-globulin antibodies, or a history of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab, bendamustine hydrochloride, or obatoclax mesylate

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness and/or social situations that would limit compliance with study requirements

• HIV infection allowed provided patient meets the following criteria:

  • No evidence of co-infection with hepatitis B or C
  • CD4 cell count ≥ 400/mm³
  • No evidence of resistant strains of HIV
  • HIV viral load ≤ 10,000 copies HIV RNA/mL for patients not on anti-HIV combination antiretroviral therapy OR HIV viral load ≤ 50,000 copies HIV RNA/mL for patients on anti-HIV therapy
  • No history of AIDS-defining conditions
• No active secondary malignancy except for non-melanomatous skin cancer
• No other concurrent investigational agents
• Prior bendamustine hydrochloride allowed provided patient has completed a bendamustine-containing regimen within the past 6 months and achieved a partial response or better
• More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered