For the first time patients have been treated in a Phase III, multicenter, randomized, open-label clinical trial with CPX-351 (cytarabine:daunorubicin; Celator Pharmaceuticals) Liposome Injection vs. conventional cytarabine and daunorubicin therapy (“7+3”) as first-line therapy in patients 60-75 years old with high-risk (secondary) acute myeloid leukemia.

Acute Myeloid Leukemiaor AML is defined as a quickly progressing disease in which too many immature white blood cells (not lymphocytes) are found in the blood and bone marrow. In 2008about13,290 new cases of AML were reported and 8,820 patients with the disease died in the US.

CPX-351 Liposome Injection represents a new approach to developing combinations of drugs in which drug molar ratios with synergisticanti-tumor activity are encapsulated in a drug delivery vehicle in order to maintain the desired ratio following administration. Theliposomal formulation of CPX-361 isa 5:1 ratio a of cytarabine and daunorubicin, two agents commonly used to treat hematologic malignancies. Researchhas shown that cytarabine:daunorubicinadministered in this ration delivers a synergistic benefit.

Orphan drug status
The new phase III trial drug has been granted orphan drug status by both the United States and the European Union and has completed two randomized, controlled, phase II clinical studies for the treatment of acute myeloid leukemia (AML).

Clinical trials
One study compared CPX-351 to the standard ‘7+3″ regimen of cytarabine:daunorubicin in patients 60-75 years of age with newly diagnosed AML and the other compared CPX-351 vs. intensive salvage therapy in first relapse AML patients 18-65 years of age. The study in patients with first relapse AML was supported by The Leukemia & Lymphoma Society?, which is also collaborating in the planned Phase III study of CPX-351 versus 7+3 in elderly patients with high risk (secondary) AML through its Therapy Acceleration Program (TAP)?.

Unique protocol
In the new phase III trial the first patients were enrolled by Stefan K. Barta, M.D., assistant professor of medicine atMontefiore Medical Center of the Albert Einstein College of Medicine. “Having observed how active CPX-351 was in the Phase II studies, we are pleased to be able to continue its evaluation and give eligible patients access to this protocol,” Barta said.

“Clinical studies completed to date suggest that CPX-351 may provide an opportunity to improve outcomes in AML, particularly for high-risk patients whose prognosis on standard therapy is poor,” said Arthur C. Louie, M.D., chief medical officer at Celator Pharmaceuticals. “This Phase III trial is a critical opportunity to confirm those prior findings.”

The study is designed to enroll patients between the ages of 60 and 75 who have pathological diagnosis of AML according to WHO criteria (with at least 20% blasts in the peripheral blood or bone marrow) with confirmation of therapy-related AML with a history of myelodysplasia (MDS), a history of chronic myelomonocytic leukemia (CMMoL) and De novo AML with karyotypic abnormalities characteristic of MDS

Patients will be randomized 1:1 to receive either CPX-351 (100u/m2; Days 1, 3, and 5 by 90 minute infusion) or 7+3 (cytarabine 100mg/m2/day by continuous infusion for 7 days and daunorubicin 60mg/m2 on days 1, 2, and 3). Patients will be monitored for all clinical adverse events as well as laboratory evaluations. The primary efficacy endpoint of the study is overall survival. The study will be conducted in the United States and Canada with approximately 50 leading cancer centers expected to participate.

“The initiation of this study is an important milestone for CPX-351 and for Celator. We hope the data it provides will allow us to seek regulatory approval for CPX-351 and, ultimately, make an important and much-needed treatment option available to patients with AML,” said Scott Jackson, chief executive officer of Celator Pharmaceuticals. “We are grateful for the enthusiastic participation of so many outstanding investigators and institutions, for the strong, ongoing support of LLS, and especially for the patients who will participate.”

Clinical trials
NCT01696084 – Phase III Study of CPX-351 Versus 7+3 in Patients 60-75 Years Old With Untreated High Risk (Secondary) Acute Myeloid Leukemia (301)
NCT00822094 – Trial of CPX-351 in Adult Patients With First Relapse Acute Myeloid Leukemia (AML)
NCT00389428 – Multicenter Study of CPX-351(Cytarabine:Daunorubicin) Liposome Injection in Patients With Advanced Hematologic Cancer.
NCT00788892 – Trial of CPX-351 in Newly Diagnosed Elderly AML Patients
NCT00875693 – A Novel Sequential Treatment of Salvage and Reduced Intensity Conditioning (RIC) Chemotherapy for Allogeneic Stem-Cell Transplantation (SCT) for Primary Refractory and Relapsed Acute Myelogenous Leukemia (AML)

Photo: Stefan K. Barta, M.D., assistant professor of medicine at Montefiore Medical Center of the Albert Einstein College of Medicine. Photo courtesy: Montefiore Medical Center/Albert Einstein College of Medicine.

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