A Phase II Study of Clofarabine in Patients With Aggressive Non-Hodgkin's Lymphoma
This study will determine the efficacy of clofarabine as measured by response rate in patients with aggressive non-Hodgkin's lymphoma
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Clofarabine in Patients With Aggressive Non-Hodgkin's Lymphoma|
- Response rate [ Time Frame: up to two years ] [ Designated as safety issue: No ]
- Determine the toxicity of clofarabine administered in conjunction with growth factor support in patients with relapsed/refractory aggressive NHL. [ Time Frame: up to two years ] [ Designated as safety issue: Yes ]
- determine the effect of clofarabine on T-, B-, and natural killer (NK)-cell subsets and quantitative immunoglobulin levels after prolonged administration of clofarabine in patients with NHL. [ Time Frame: up to two years ] [ Designated as safety issue: No ]
- Assess cytokine (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and IL-10) release following clofarabine therapy. [ Time Frame: up to two years ] [ Designated as safety issue: No ]
- Assess the effect of pre-treatment prognostic factors (p53 mutational status, DNA methylation, and apoptotic protein levels) in patient-derived tumor tissue on response to clofarabine. [ Time Frame: up to two years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2004|
|Study Completion Date:||June 2006|
|Primary Completion Date:||May 2006 (Final data collection date for primary outcome measure)|
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.