Data from Phase I clinical trial of Quadramet in patients with relapsed multiple myeloma presented

07-19-2006

Cytogen Corporation (CYTO) announced interim results from a Phase I clinical trial of Quadramet (samarium Sm-153 lexidronam injection) in combination with bortezomib (Velcade, Millennium Pharmaceuticals, Inc.) in patients whose multiple myeloma has relapsed following prior treatment.

Data from the ongoing study indicate that the combination regimen, known as VELSAM, was well tolerated at doses studied to date and demonstrated anti-tumor activity, with fifty percent of patients experiencing a response or achieving stable disease. Results were presented at the 11th Congress of European Hematology, organized by the European Hematology Association (EHA).

"As we gain additional experience with patients receiving multiple cycles of treatment, we continue to be impressed not only by the responses observed in this heavily pretreated population of patients but also by the patient-friendly nature of this treatment regimen," said principal investigator James Berenson, MD, medical & scientific director of the Institute for Myeloma & Bone Cancer Research in West Hollywood, California.

The study involves patients with multiple myeloma whose disease has progressed or is refractory to prior therapy and is designed to examine the safety, tolerability, efficacy and anti-tumor effects of Quadramet in combination with bortezomib. A treatment cycle consists of injections of bortezomib on days one, four, eight and eleven with a single dose of Quadramet administered on day three. No additional injections of bortezomib or Quadramet are given for eight weeks. Patients may receive up to four cycles of study treatment.

By way of comparison, bortezomib monotherapy is typically administered on days one, four, eight and eleven of a treatment cycle that is repeated every three weeks, typically for six to eight cycles.

The data reported was from 12 patients in four separate dose groups who have completed at least one eight-week cycle of Velsam treatment. There are two arms to the study: Arm one with bortezomib at 1.0 mg/m2 and Arm two with bortezomib at 1.3 mg/m2. Both arms use escalating doses of Quadramet (0.25 mCi/kg, 0.5 mCi/kg, and 1.0 mCi/kg). Patients are enrolled alternately into parallel cohorts.

Responses are assessed using Blade criteria - a rigorous assessment standard used to describe changes in disease status, including a confirmation six weeks later. A "complete response" required 100% disappearance of M-protein (a marker of tumor burden); negative immunofixation testing; less than 5% plasma cells in the bone marrow; no increase in size or number of lytic bone lesions; and disappearance of soft tissue tumors (plasmacytomas). "Partial" remissions and "minimal" responses represented lesser degrees of response based on the same criteria. Worsening of these indicators constituted "progressive disease."

The poster presentation titled "Phase I Study of Bortezomib and 153Sm-lexidronam Combination for Refractory and Relapsed Multiple Myeloma," was presented at the EHA meeting during a session titled "myeloma and other monoclonal gammopathies III" and reported the following results:

- Twelve patients have been treated thus far at Quadramet doses of 0.25 and 0.5 mCi/kg. The standard approved dose of Quadramet for palliation of bone pain is 1.0 mCi/kg;

- Patients had progressive disease despite receiving an average of 3.5 prior treatment regimens (median 3, range 1-8) for their myeloma and eight of the twelve had relapsed following prior treatment with bortezomib;

- Two patients received more than one VELSAM treatment cycle;

- One patient who received 0.5 mCi/kg of QUADRAMET and 1.0 mg/m2 of bortezomib achieved a complete response and another who received 0.25 mCi/kg of QUADRAMET and 1.3 mg/m2 of bortezomib achieved a partial response as defined by Blade criteria;

- Four additional patients, including all three who received 0.5 mCi/kg of Quadramet and 1.3 mg/m2 of bortezomib achieved a stabilization of their disease;

- Of the six patients that experienced a response or achieved stable disease, three had previously failed treatment with bortezomib alone; and

- Toxicities have generally been transient and manageable.

"We are pleased with the progress of this study and the interim results reported in this poster presentation," said William Goeckeler, PhD, senior vice president of operations at Cytogen and co-author of the presentation. "Patients are receiving additional treatment cycles and the study continues to rapidly accrue patients at higher Quadramet dose levels. We look forward to reporting additional results at scientific meetings later this year."

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2006, Pain & Central Nervous System Week via NewsRx.com.