Rituximab, Ifosfamide, Carboplatin, and Etoposide (RICE) Followed by Gallium Nitrate, Rituximab and Dexamethasone (GARD) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma

This is a Phase 2 trial evaluating the efficacy of adding the combination of GaRD x 2 cycles
following 3 cycles of the standard salvage regimen of RICE for the treatment of relapsed or
refractory diffuse, large B-cell lymphoma (DLBCL). The study will include patients who have
relapsed after 1 prior treatment regimen or who are refractory to initial chemotherapy. We
will evaluate patients for response rate (both partial and complete), toxicities, as well as
overall and progression free survival. Eligible patients will receive standard RICE x 3
cycles followed by GaRD x 2 cycles. Patients who would otherwise be eligible, may then
proceed to autologous stem cell transplant (ASCT).

Inclusion Criteria:

- Must have histologically or cytologically confirmed diffuse, large B-cell lymphoma
(WHO classification diffuse large B-cell lymphoma or mediastinal large B-cell
lymphoma), immunoblastic B cell lymphoma or Burkitts lymphoma. Transformed, large
B-cell lymphoma will be excluded.

- Must have measurable disease, defined as at least one lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded) as >10 mm with
spiral CT scan.

- Must be refractory to initial therapy or have disease relapse from prior therapy and
must be at least 3 weeks post treatment from prior chemotherapy or radiation therapy.

- Age >18 years.

- Life expectancy >24 weeks

- SWOG performance status <1 (Karnofsky >80%).

- Must have normal organ function (or impaired marrow function) as defined below:

- leukocytes > or equal to 1,500/mcL

- absolute neutrophil count >or equal to 1,000/mcL

- platelets >or equal to 50,000/mcL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) due to lymphoma involvement

- creatinine clearance > than or equal to 60 mL/min

- Must agree not to become pregnant for the duration of study participation.

- Ability to understand and the willingness to sign a written informed consent
document.

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study.

- Follicular B-cell lymphomas, small lymphocytic lymphomas, chronic lymphocytic
leukemia, lymphoblastic lymphomas and all T-cell lymphomas.

- Patients may not be receiving any other investigational agents, within trials in the
previous 4 weeks.

- Patients with known CNS metastases are excluded from this clinical trial.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to gallium nitrate, rituximab, dexamethasone, ifosfamide, carboplatin,
and/or etoposide.

- Prior therapy with gallium nitrate, ifosfamide, carboplatin and/or etoposide

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant and women who are nursing are excluded from this study.

- Because patients with immune deficiency are at increased risk of lethal infections
when treated with marrow-suppressive therapy, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with RICE and/or GaRD.