Pixantrone Versus Doxorubicin in CHOP-R Therapy for First-line Treatment of Aggressive Non-Hodgkin's Lymphoma Preliminary Results Presented at American Society of Hematology (ASH) Annual MeetingThree-fold Lower Incidence of Severe Cardiac Toxicity With Equivalent Complete Remission Rates Reported
ATLANTA, December 11, 2007 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (CTI) announced today that preliminary data from its phase II/III randomized study comparing CPOP-R to CHOP-R in the first-line treatment of patients with aggressive non-Hodgkin's lymphoma (NHL) showed patients who received pixantrone experienced less severe (grade 3/4) toxicities including severe infection and febrile neutropenia when compared to patients treated with standard doxorubicin-based therapy. A preliminary analysis of the study, known as PIX203, which is ongoing, was presented at the American Society of Hematology (ASH) Annual Meeting in Atlanta.
"While preliminary, these randomized trial results are encouraging in supporting the preclinical findings that pixantrone is associated with a lower incidence of severe cardiac damage as evidenced by substantial declines in ejection fraction than standard anthracylines such as doxorubicin when administered as part of combination chemotherapy in the front line treatment of aggressive NHL," said Jack W. Singer, Chief Medical Officer of CTI. "Although preliminary, these data suggest that there may be reductions in other clinically important toxicities such as febrile neutropenia and severe infections without a loss in anti-tumor activity. These findings, along with its robust preclinical profile, suggest that pixantrone is an ideal drug candidate for further investigation in clinical trials for NHL, breast cancer and other diseases where anthracyclines are standard of care."
CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) Compared to CPOP-R (cyclophosphamide, pixantrone, vincristine, prednisone, rituximab) in 1st Line Therapy of Diffuse Large B cell Lymphoma (DLBCL): An Interim Analysis
Data were presented that show CPOP-R had comparable anti-tumor activity to CHOP-R with fewer severe side effects. In the interim analysis, 78 patients were evaluated for safety and 40 patients were evaluated for efficacy. A reduction in the incidence of severe heart damage (LVEF decline >15 percent, 2/36 patients for CPOP-R vs. 7/36 patients for CHOP-R) was seen. Declines in LVEF greater than or equal to 10% have occurred equally in both arms (8 patients each). In addition, reductions in grade 3 infections (2 patients for CPOP-R vs. 7 patients for CHOP-R) and febrile neutropenia (2 patients for CPOP-R vs. 7 patients for CHOP-R) were reported in this early interim analysis.
Based on investigator assessments after four cycles of therapy, 40 patients were evaluated for efficacy, of which 33 percent achieved a complete response (CR) and 53 percent achieved a partial response (PR) on the CPOP-R arm (n=21) compared to 32 percent achieving a CR and 52 percent achieving a PR on the doxorubicin arm (n=19).
There were three deaths within 30 days of the last dose of study treatment on the CPOP-R arm. Two of the events were attributed to study treatment (pneumonia concurrent with neutropenia and non-cardiogenic pulmonary edema concurrent with non-neutropenic infection). No deaths within 30 days of the last dose of the study drug were reported in the CHOP-R arm.
Details of the RAPID Trial
The RAPID (Replacing Adriamycin with Pixantrone to Improve Safety in NHL Disease) trial is a randomized controlled phase II/III combination study in up to 280 patients investigating whether the substitution of pixantrone for doxorubicin in the first-line treatment of patients with advanced aggressive NHL can provide a comparable major response rate while reducing known clinically important doxorubicin-related toxicities. This multi-center international trial randomizes newly diagnosed patients to either the standard of care regimen CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) or an investigational regimen which replaces doxorubicin with pixantrone, CPOP-R (cyclophosphamide, pixantrone, vincristine, prednisone, and rituximab) monthly for six cycles. During treatment, patients are evaluated for response to therapy after cycle 4 and at the end of treatment. During follow up disease status is assessed every three months during first year and every six months thereafter.
Cardiac function, as determined by serial multi-gated nuclear scans (MUGA), is evaluated prior to initiation of therapy and then at the completion of every two cycles of therapy. Thus far, routine prophylactic administration of G-CSF was utilized equally across treatment arms in approximately half of study participants. The interim analysis was conducted after at least four cycles of therapy to determine if the dose of pixantrone (150 mg/m2) was adequate to induce major objective responses comparable to the doxorubicin arm as well as to evaluate potential differences in major toxicities. Members of the independent Data Safety Monitoring Board (DSMB) review safety data on a quarterly basis.
Pixantrone in Clinical Studies
There are currently two clinical studies of pixantrone in aggressive NHL patients, RAPID and a phase III single agent trial, known as EXTEND. The EXTEND trial explores the role of single-agent treatment as a salvage regimen in patients with relapsed aggressive NHL who have failed at least two prior treatment regimens. Patients are randomized to receive either pixantrone or another single-agent drug of the physician's choice currently used for the treatment of this patient population.
A phase III trial of pixantrone for patients with indolent NHL was launched in September 2007. The trial, PIX303, will examine the complete remission rates and time to disease progression for the combination regimen of fludarabine, pixantrone and rituximab (FP-R) compared to the combination of fludarabine and rituximab (F-R) in the treatment of patients who have received at least one prior treatment for NHL. The trial is expected to enroll 300 patients.
Pixantrone is an investigational agent under development for the potential treatment of various hematological malignancies. It was developed to improve the activity and safety of the anthracycline family of anti-cancer agents. Anthracyclines have been shown to be very active clinically in a number of tumor types. However, they are usually associated with cumulative heart damage that prevents them from being used in a large proportion of patients. Pixantrone has been designed to reduce the potential for these severe cardiotoxicities, as well as to potentially increase activity and permit simplified administration compared to the currently marketed anthracyclines.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit http://www.cticseattle.com.
This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of pixantrone include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with pixantrone in particular including, without limitation, the potential failure of the final results of the RAPID clinical study of pixantrone to have the same or similar results to the interim analysis, or the potential failure of pixantrone to prove safe and effective for treatment of non-Hodgkin's lymphoma or other cancers, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling pixantrone, and the risk factors listed or described from time to time in the Company's filings with the Securities and Exchange Commission including, without limitation, the Company's most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by Italian law, CTI is under no obligation to (and expressly disclaims any such obligation to) update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.
Media Contact: Dan Eramian T: 206.272.4343 C: 206.854.1200 Susan Callahan T: 206.272.4472 F: 206.272.4434 E: http://www.cticseattle.com/media.htm Investors Contact: Leah Grant T: 206.282.7100 F: 206.272.4434 E: http://firstname.lastname@example.org email@example.com
CONTACT: media, Dan Eramian, +1-206-272-4343, cell, +1-206-854-1200, orSusan Callahan, +1-206-272-4472, fax, +1-206-272-4434, both; or investors, Leah Grant, +1-206-282-7100, fax,+1-206-272-4434, , all of Cell Therapeutics, Inc. firstname.lastname@example.org email@example.com
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Posted: December 2007