In collaboration with the Food and Drug
Administration (FDA), and as a service to our members, ASH provides information
about newly approved therapies for patients. This allows the agency to inform
hematologists and professionals in hematology-related fields of recent
approvals in a timely manner. Included in the message below is a link to the
product label, which provides the relevant clinical information on the
indication, contraindications, dosing, and safety. In providing this
information, ASH does not endorse any product or therapy and does not take any
position on the safety or efficacy of the product or therapy described. The
following is a message from the FDA’s Office of Hematology and Oncology
On August 9, 2012, the U. S. Food and Drug Administration
granted accelerated approval for vinCRIStine
sulfate LIPOSOME injection (Marqibo®, 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 Marqibo® was studied in a single
trial, HBS407, 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 complete
remission (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 were not eligible for immediate hematopoietic stem cell
transplantation. All patients had received prior vincristine sulfate; 22 (34%) had not received asparaginase products.
Fifty-one percent (51%) of patients were male, 45% were under
30 years of age and 11% were age 65 or older. Eighty-five percent had precursor
B cell ALL and 15% had precursor T cell ALL. Marqibo® was infused intravenously at 2.25 mg/m2 over60
minutesevery 7 days. Concomitant
corticosteroids were not permitted beyond Day 5.
The CR rate was 4.6% (3/65) and the CRi rate was 10.8% (7/65).
Among the 10
patients achieving CR or CRi, the median documented remission duration was 28
days (95% CI: 7, 36), and the median duration of time to the first event (relapse,
death, or subsequent chemotherapies) was 56 days (95% CI: 9, 65).
The safety of Marqibo® at the dose of 2.25 mg/m2
weekly was evaluated in two single arm trials (HBS407 and VSLI-06) consisting
of a total of 83 patients with ALL in second
or greater relapse. Adverse reactions were observed
in 100% of patients. The most common adverse reactions (>30%) were
constipation, nausea, pyrexia, fatigue, peripheral neuropathy, febrile
neutropenia, diarrhea, anemia, decreased appetite, and insomnia.
Severe adverse reactions (Grade 3 or greater) occurred in
96% of patients. The most common were infections,
neuropathy, febrile neutropenia, neutropenia, anemia, and thrombocytopenia.
Dose reduction, delay or omission occurred in 53% of
patients during the treatment.
Adverse reactions leading to
treatment discontinuation were reported in 28% of patients. The most common adverse reactions that
led to treatment discontinuation (other than leukemia-related) were peripheral
neuropathy (10%) and tumor lysis syndrome (2%).
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% in the HBS407 trial. Causes of deaths
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).
As a condition of the accelerated approval, Talon Inc. will
study the effect of Marqibo® on overall survival in a randomized
controlled trial of adult patients with ALL.
The recommended dose and schedule for Marqibo® is
a dose of 2.25mg/m2, intravenously, over 1 hour once
every 7 days.
prescribing information, including clinical trial information, safety, dosing,
drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202497s000lbl.pdf
Healthcare professionals should report all serious adverse
events suspected to be associated with the use of any medicine and device to
FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm,
by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided
online, or by telephone (1-800-FDA-1088).
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