FDA Approves New Drug Labeling for Fludarabine Phosphate in CLL

The FDA has approved updated drug labeling for fludarabine phosphate under Project Renewal.¹

Fludarabine Phosphate Injection is now approved for use as a component of a combination regimen for the treatment of adults with B-cell chronic lymphocytic leukemia (CLL); and for the treatment of adults with B-cell CLL who have not responded to or whose disease has progressed during treatment with at least 1 alkylating-agent containing regimen.

In addition, the FDA amended the existing label to include the recommended dosage for use in combination with cyclophosphamide and rituximab (Rituxan. The boxed warning was also removed, and this information was incorporated in the Warnings and Precautions section.

The recommended dose in adults is 25 mg/m² administered intravenously over approximately 30 minutes daily for 5 consecutive days.² Each treatment course should begin every 28 days. In accordance with the label, the dose should be reduced in patients with creatinine clearance between 30 and 70 mL/min/l.73 m². The drug should not be used in patients with severe renal impairment.

The efficacy of fludarabine phosphate was evaluated in 2 single-arm, open-label studies in adult patients with CLL who were refractory to at least 1 prior standard alkylating agent–containing regimen. In the first study, conducted by The University of Texas MD Anderson Cancer Center (MD Anderson), 48 patients received between 22 mg/m² and 40 mg/m² of fludarabine phosphate daily for 5 days every 28 days. In the second study, conducted by the Southwest Oncology Group (SWOG), 31 patients received between 15 mg/m² and 25 mg/m² of fludarabine phosphate daily for 5 days every 28 days.

The objective response rates were 48% and 32% in the MD Anderson and SWOG studies, respectively, according to response criteria developed by the National Cancer Institute CLL Working Group. The complete response rate in both studies was 13%; the partial response rate was 35% in the MD Anderson study and 19% in the SWOG study.

The median time to response in the MD Anderson and SWOG studies was 7 weeks (range, 1-68) and 21 weeks (range, 1-53), respectively. The median duration of disease control was 91 weeks and 65 weeks in the MD Anderson and SWOG studies, respectively. The median survival among all patients with refractory CLL who received fludarabine phosphate in the MD Anderson and SWOG studies was 43 weeks and 52 weeks, respectively.

Moreover, Rai stage improved to stage II or better in 7 of 12 responders (58%) in the MD Anderson study and in 5 of 7 responders (71%) in the SWOG study who had stage II or IV disease at baseline. In the collective cohort of both study populations, the mean hemoglobin concentration improved from 9.0 g/dL at baseline to 11.8 g/dL at the time of response in a subgroup of patients with anemia. Additionally, the average platelet count improved from 63,500/mm³ to 103,300/mm³ at the time of response in a subgroup of patients who had thrombocytopenia at baseline.

Regarding safety, common adverse effects include myelosuppression, fever and chills, fatigue, weakness, infection, pneumonia, cough, nausea, vomiting and diarrhea. Other frequently reported events include malaise, mucositis, and anorexia.

References

1. FDA approves updated drug labeling for fludarabine phosphate under Project Renewal. FDA. Updated November 20, 2024. Accessed November 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-updated-drug-labeling-fludarabine-phosphate-under-project-renewal?utm_medium=email&utm_source=govdelivery
2. Fludarabine Phosphate Injection. Prescribing information. Sandoz; 2010. Accessed November 20, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022137s003lbl.pdf