Trial Information

A Phase II Study of Clofarabine in Patients With Aggressive Non-Hodgkin's Lymphoma

Rationale: Two Food and Drug Administration drugs approved for blood cancers such as
non-Hodgkin's lymphoma (NHL) include fludarabine (Fludara) and cladribine (Leustat). The
drug offered in the current study, clofarabine was designed to combine the anti-cancer
strength of both fludarabine and cladribine. Laboratory research suggests that clofarabine
targets anti-cancer mechanisms in cells, helps repair DNA, and inhibits tumor growth.
Research also indicates that clofarabine has some efficacy against a variety of blood
cancers and solid tumors. Numerous tumor responses have been observed with high doses of
clofarabine in heavily pretreated patients with different types of lymphoma. The current
study build on this previous research to test clofarabine in patients with aggressive NHL.

Purpose: This study will evaluate the safety and efficacy of clofarabine for aggressive NHL.
Toxicities resulting from the combination of clofarabine and the supportive care drug GM-CSF
will also be analyzed in patients. GM-CSF is a blood-forming agent that stimulates the
production of white blood cells. In addition, several tests, including blood and tumor
tissue analysis, will assess immune response and biological changes to the tumor as a result
of study drugs.

Treatment: Patients in this study will be given clofarabine through intravenous infusions.
This drug will initially be provided to patients for five consecutive days. Several tests
will then be conducted and supportive care agents will be administered to stabilize
patients' blood cell counts, immune response, and reduce the risk of infection. The first
ten patients in this study will be hospitalized until recovery from the first five days of
clofarabine to carefully monitor any additional toxicities resulting from the dosing
regimen. Patients will receive another five day treatment cycle with clofarabine within
seven days after recovering from each previous cycle and no more than four weeks from the
start of the previous cycle. Disease response will be measured after every two cycles of
treatment with clofarabine. Patient with stable or reduced disease will receive a maximum of
six treatment cycles with clofarabine. Treatments will be discontinued due to disease
growth, unacceptable side effects, or a treatment delay of more than 21 days.