3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma

PRIMARY OBJECTIVES:

I. To determine the maximal tolerable dose (MTD) of 3-AP administered as a 24 hour infusion
in combination with and fixed-dose gemcitabine hydrochloride (GEM) in patients with advanced
solid tumors or lymphomas.

SECONDARY OBJECTIVES:

I. To define the qualitative and quantitative toxicities of the 3-AP/GEM combination in
regard to organ specificity, time course, predictability, and reversibility.

II. To document the therapeutic response of this combination in those patients when
possible.

III. To measure deoxycytidine triphosphate (dCTP) levels in peripheral blood mononuclear
cells (PBMCs) before and after treatment at specified times and try to correlate findings to
activity and toxicity of 3-AP.

IV. To perform limited pharmacokinetic analysis.

OUTLINE: This is a dose-escalation study of 3-AP (Triapine®).Patients receive 3-AP
(Triapine®) IV over 24 hours followed by gemcitabine hydrochloride IV over 100-125 minutes
on days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease
progression or unacceptable toxicity.

Patients achieving complete response (CR) receive 1 additional course of therapy beyond
documented CR.Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine®) until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.After completion of study
treatment, patients are followed periodically for 2 years.

Inclusion Criteria:

- Histologically or cytologically confirmed advanced solid tumors or lymphoma

- Disease considered incurable using standard treatment

- ECOG performance status ≤ 2

- Life expectancy > 12 weeks

- WBC ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Total bilirubin normal

- AST/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 contraception prior to and during study treatment

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to 3-AP (Triapine®) and/or gemcitabine hydrochloride

- No known glucose-6-phosphate dehydrogenase (G6PD) deficiency

- No 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 situation that would limit compliance with
study requirements

- No pulmonary disease (e.g., dyspnea at rest, supplemental oxygen requirement, or
baseline oxygen saturation < 92%)

- Prior gemcitabine hydrochloride allowed if given as a standard 30-minute infusion

- At least 4 weeks since prior gemcitabine hydrochloride

- Patient may have received < 2 lines of chemotherapy in the metastatic setting

- No prior 3-AP (Triapine®) or fixed-dose gemcitabine hydrochloride

- At least 6 weeks since prior nitrosoureas or mitomycin C

- More than 3 weeks since prior radiotherapy

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy in HIV-positive patients

- No other concurrent anticancer agents or therapies