Phase 2 Multicenter Trial of Gallium Nitrate in Patients with Advanced Non-Hodgkin’s Lymphoma (NHL).

While approved for treatment of cancer-related hypercalcemia, gallium nitrate (Ganite®; GN) has displayed broad antitumor activity as a single agent in Phase 2 trials, particularly in patients (pts) with bladder disease, Hodgkin’s disease, and NHL who received GN by bolus or continuous IV infusion (CIVI). To establish the safety profile and clincial activity in a large cohort of patients with a wide variety of histologies, we conducted a Phase 2 study in pts with both T- and B-cell lymphoma who had relapsed from standard anti-lymphoma therapy.

Eligibility criteria included: relapsed NHL; ECOG PS ≤ 2; measurable disease; adequate renal and hepatic function. GN was administered by CIVI daily via ambulatory infusion pump x 7 days every 3 wks at 1 of 2 daily dose levels, 200 or 300 mg/m²/d. Evaluation for efficacy required treatment with ≥ 2 cycles; all treated pts were considered evaluable for safety. A total of 88 pts were accrued to the trial, 44 pts at each dose level. Pt characteristics included: median age, 61 yrs (range 19–83); median prior regimens, 5 (range 1–13); median prior drugs, 9 (range, 1–15); median prior rituximab regimens, 2 (range, 1–6); no. of pts with prior stem cell transplant, 25 (28%); no. of pts with prior radiation therapy, 29 (33%).

At the 300 mg/m² dose level, 30 pts are evaluable for response. The ORR in this dose level was 30% (7% CR or uCR), including 3/12 pts with diffuse LCL (DLCL) (2 post-BMT), 3/11 with follicular lymphomas (1 post-BMT), 2/3 pts with mantle cell NHL (1 CR), 0/2 pts with SLL, and 1/2 pts with peripheral T-cell NHL (1 uCR). The results in the 200 mg/m² dose level are preliminary and currently under evaluation.

Most frequent (> 10%) grade 3/4 adverse reactions (through July 2004) included: anemia (32%); hypocalcemia (19%) (occasionally requiring parenteral replacement with Ca⁺⁺ and Mg⁺⁺); dyspnea (15%); and hypotension (11%). Optic neuritis or visual disturbance occurred in 4 pts: 3 pts at the 300 mg/m² dose level (after 2, 3 and 6 cycles, respectively) and 1 pt at the 200 mg/m² dose level (after 7 cycles). All patients discontinued therapy as a consequence of this adverse event; two pts were treated with high-dose corticosteroids. All patients improved after discontinuation.

These results demonstrate that gallium nitrate is an active and well tolerated agent in a heavily pretreated population of patients with NHL and suggest that it may be particularly useful in patients who cannot tolerate myelosuppressive regimens.