FDA Approval for Vincristine Sulfate Liposome
Brand name(s): Marqibo®
- Approved for adults with Philadelphia chromosome-negative
(Ph –) acute lymphoblastic leukemia (ALL)
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.
On August 9, 2012, the Food and Drug Administration (FDA) granted accelerated approval for vincristine sulfate liposome injection (Marqibo®, made by Talon Therapeutics, Inc.) for the treatment of adult patients with Philadelphia chromosome-negative (Ph –) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies.
The approval is based on the rate of complete remission (CR) plus the rate of complete remission with incomplete blood count recovery (CRi) in a single-arm, single-agent trial of 65 adults in second or greater relapse.
The efficacy of vincristine sulfate liposome was studied in the HBS407 trial, which enrolled patients age 18 years or older with Philadelphia chromosome-negative ALL in second or greater relapse or whose disease progressed after two or more anti-leukemia treatment regimens. Patients had to have achieved a CR from one of the prior anti-leukemia chemotherapies, defined by a leukemia-free interval of at least 90 days. At the time of screening and enrollment, patients had to be ineligible for immediate hematopoietic stem cell transplantation. All patients had received prior vincristine sulfate; 22 (34 percent) had not received asparaginase products.
Fifty-one percent of patients were male, 45 percent were under 30 years of age, and 11 percent were age 65 or older. Eighty-five percent of patients had precursor B-cell ALL, and 15 percent had precursor T-cell ALL. Vincristine sulfate liposome was infused intravenously at 2.25 mg/m2 over 1 hour every 7 days. Concomitant corticosteroids were not permitted beyond day 5 of the first course.
The CR rate was 4.6 percent (three patients) and the CRi rate was 10.8 percent (seven patients). Among the 10 patients who achieved CR or CRi, the median documented remission duration was 28 days (95 percent CI: 7, 36), and the median duration of time to first event (relapse, death, or subsequent chemotherapies) was 56 days (95 percent CI: 9, 65).
The safety of vincristine sulfate liposome at the dose of 2.25 mg/m2 weekly was evaluated in HBS407 and VSLI-06 (an earlier phase I/II trial) that included a total of 83 patients with ALL in second or greater relapse. Adverse reactions were observed in 100 percent of patients. The most common adverse reactions (more than 30 percent) were constipation, nausea, pyrexia, fatigue, peripheral neuropathy, febrile neutropenia, diarrhea, anemia, decreased appetite, and insomnia.
Dose reduction, delay or omission occurred in 53 percent of patients during the treatment.
Adverse reactions leading to treatment discontinuation were reported in 28 percent of patients. The most common adverse reactions that led to treatment discontinuation (other than leukemia-related) were peripheral neuropathy (10 percent) and tumor lysis syndrome (2 percent). Adverse reactions related to neuropathy and leading to treatment discontinuation included decreased vibratory sense, facial palsy, hyporeflexia, constipation, asthenia, fatigue, and musculoskeletal pain.
Deaths occurred in 23 percent of patients in the HBS407 trial. Causes of death were brain infarct (1), intracerebral hemorrhage (2), liver failure (1), multi system organ failure (2), pneumonia and septic shock (3), respiratory failure (4), pulmonary hemorrhage (1), and sudden cardiac death (1).
The recommended dose and schedule for vincristine sulfate liposome is a dose of 2.25 mg/m2, intravenously, over 1 hour once every 7 days.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.