Obatoclax and Bortezomib in Treating Patients With Aggressive Relapsed or Recurrent Non-Hodgkin Lymphoma

Inclusion Criteria:

• Histologically or cytologically confirmed relapsed or refractory non-Hodgkin lymphoma for which standard curative or palliative measures do not exist or are no longer effective, including any of the following subtypes:

  • Follicular grade I, II, or III lymphoma
  • Marginal zone lymphoma
  • Mantle cell lymphoma
  • Diffuse large B cell lymphoma
  • Small lymphocytic lymphoma

• Must have had at least one prior chemotherapeutic regimen:

  • Steroids or rituximab alone or local radiotherapy do not count as regimens
  • Tositumomab or ibritumomab tiuxetan allowed as regimens
• Clear evidence of disease progression or lack of response after the most recent therapy, including rituximab or local radiotherapy, is required
• At least 3 months since prior autologous stem cell transplantation and relapsed (>= 1 year since prior allogeneic transplantation and relapsed) and no active related infections (i.e., fungal or viral)
• In the case of allogeneic transplantation relapse, there should be no active acute graft-versus-host disease (GVHD) of any grade and no chronic GVHD other than mild skin, oral, or ocular GVHD not requiring systemic immunosuppression
• No known active brain metastases, other neurological disorders/dysfunction or history of seizure disorder, or other neurological dysfunction
• Karnofsky performance status 60-100%
• Life expectancy > 3 months
• Total bilirubin normal
• AST and ALT =< 2.5 times upper limit of normal
• Creatinine normal or creatinine clearance >= 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 3 months after the last dose of obatoclax mesylate
• At least 4 weeks since prior radiotherapy
• More than 2 days since prior steroids
• More than 2 weeks since prior low-dose chlorambucil
• WBC >= 3,000/mm^3
• ANC >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• At least 2 weeks since prior valproic acid

Exclusion Criteria:

• Uncontrolled concurrent medical condition or illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia including QTc > 450 msec
• Patients who are intolerant or refractory to prior treatment with bortezomib (refractory is defined as no response to prior treatment with bortezomib)
• Chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
• Rituximab within the past 3 months (unless there is evidence of progression)
• Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Other concurrent investigational agents
• Combination antiretroviral therapy for HIV-positive patients
• No history of allergic reactions attributed to bortezomib, polyethylene glycol (PEG 300), or polysorbate 20
• No psychiatric illness or social situation that would limit compliance with study requirements