Phase I Study of GX15-070 (NSC # 729280) and Bortezomib in Aggressive Relapsed/Recurrent Non-Hodgkin's 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