3 January 2019 - - The US Food and Drug Administration has expanded the indication for Sprycel (dasatinib) tablets to include the treatment of pediatric patients one year of age and older with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia in combination with chemotherapy, US-based pharmaceutical company Bristol-Myers Squibb Company (NYSE: BMY) said.

Sprycel is the only second-generation tyrosine kinase inhibitor approved for this patient population. The approval, which was granted following priority review by the FDA, is based on data from the Phase 2 study, CA180-372 (NCT01460160).

Sprycel is associated with the following Warnings and Precautions: myelosuppression, bleeding-related events, fluid retention, cardiovascular events, pulmonary arterial hypertension, QT prolongation, severe dermatologic reactions, tumor lysis syndrome, embryo-fetal toxicity and effects on growth and development in pediatric patients.1Please see detailed Important Safety Information below.

The efficacy of Sprycel tablets in combination with chemotherapy was evaluated in a single cohort of the Phase 2, multicenter, single-arm CA180-372 study, which included 78 pediatric patients with newly diagnosed B-cell precursor Ph+ ALL.1,2 At three years, the study demonstrated an event-free survival binary rate of 64.1% (95% confidence interval [CI]: 52.4 to 74.7).

Event-free survival is defined as the time from the start of Sprycel to lack of complete response at the end of the third high-risk block, relapse, secondary malignancy or death from any cause.

Of the 81 patients evaluated for safety, fatal adverse reactions occurred in three patients, and eight experienced adverse reactions leading to treatment discontinuation, including fungal sepsis, hepatotoxicity of graft versus host disease, thrombocytopenia, CMV infection, pneumonia, nausea, enteritis and drug hypersensitivity.1The most common serious adverse reactions (incidence ≥10%) were pyrexia, febrile neutropenia, mucositis, diarrhea, sepsis, hypotension, infections (bacterial, viral and fungal), hypersensitivity, vomiting, renal insufficiency, abdominal pain and musculoskeletal pain.

Acute lymphoblastic leukemia is characterized by chromosomal abnormalities and genetic alterations involved in the differentiation and proliferation of lymphoid precursor cells.

The most common childhood cancer in the United States, ALL represents 20% of all cancers diagnosed in persons aged less than 20 years, or more than 3,000 new cases each year.

Three percent of children who have ALL have the Ph+ subtype, which means they have a chromosome alteration that results in a specific mutation of the BCR-ABL gene.

In addition to this pediatric approval, Sprycel is approved for use in children one year of age and older with Ph+ chronic myeloid leukemia in chronic phase.

In the CA180-372 trial, the 78 patients evaluated for efficacy in cohort 1 received Sprycel at a daily dose of 60 mg/m2 for up to 24 months, in combination with chemotherapy.

The backbone chemotherapy regimen was the AIEOP-BFM ALL 2000 multi-agent chemotherapy protocol.

Efficacy was established based on three-year EFS, defined as the time from the start of Sprycel to lack of complete response at the end of the third high-risk block, relapse, secondary malignancy or death from any cause.

The trial was designed such that patients with central nervous system 3 disease receive cranial irradiation.

Patients were assigned to receive stem cell transplant based on minimal residual disease if they were considered high-risk.

Data from the CA180-372 trial were presented at the 2017 American Society of Hematology annual meeting.

The recommended starting dosage for Sprycel in pediatric patients with Ph+ ALL is based on body weight. The recommended dose should be administered orally once daily, and the dose should be recalculated every three months based on changes in body weight, or more often if necessary.

For pediatric patients with Ph+ ALL, Spryceltherapy should begin on or before day 15 of induction chemotherapy, when diagnosis is confirmed, and continue for two years.

Sprycel tablets should not be crushed, cut or chewed.1 Tablets should be swallowed whole; however, there are additional administration considerations for pediatric patients who have difficulty swallowing tablets whole.

Five patients with Ph+ ALL 2 to 10 years of age received at least one dose of Sprycel tablet dispersed in juice on Study CA180-372. The exposure for dispersed tablets was estimated to be 36% lower as compared to intact tablets in pediatric patients. Due to the limited available clinical data, it is unclear whether dispersing Sprycel tablets significantly alters the safety and/or efficacy of Sprycel.

In the CA180-372 study, 81 pediatric patients with Ph+ ALL received Sprycel continuously in combination with chemotherapy. The median duration of therapy was 24 months (range 2 to 27 months).