Pixantrone Produces High Rates of Complete and Partial Remissions Even Among Aggressive NHL Patients With Extensive Prior Doxoru
June 02 2009 - 1:30AM
PR Newswire (US)
Panel Discussant Focuses on Longer Duration of Remission among
Patients Achieving a Complete Remission with Pixantrone than
Complete Remissions Achieved with Standard Chemotherapy ORLANDO,
June 2 /PRNewswire-FirstCall/ -- Therapeutics, Inc. ("CTI") (Nasdaq
and MTA: CTIC) announced today that at the poster and discussion
session of the Lymphoma and Plasma Cell Disorders Section at the
2009 American Society of Clinical Oncology ("ASCO") Annual Meeting,
new subgroup analysis data were reviewed from the phase III EXTEND
(PIX 301) clinical trial of pixantrone (the "PIX 301 EXTEND trial")
demonstrating the effectiveness of pixantrone as therapy in
patients with aggressive non-Hodgkin's lymphoma ("NHL") for whom
anthracycline and related drugs are typically not to be used due to
a high risk of cardiac toxicity, including cardiac failure.
Twenty-five of the 70 patients in the PIX 301 EXTEND trial had
received prior cumulative doxorubicin doses in excess of the
standard 300 mg/m2 associated with six cycles of first line CHOP
(cyclophosphamide, doxorubicin, vincristine and prednisone)
therapy. The median prior exposure of these patients, most of whom
had received an anthracycline as part of a salvage regimen, was 386
mg/m2 (with a range of 306 mg/m2 to 778 mg/m2). Following treatment
with pixantrone, ten of these 25 patients (40%) achieved a
confirmed complete remission ("CR"), unconfirmed remission ("CRu")
or partial remission ("PR") (CR=2, CRu= 5, 28%; PR=3, 12%) The
lifetime cumulative doxorubicin equivalent dose following
pixantrone was 579 mg/m2 (with a range of 361 mg/m2 to 1003 mg/m2).
No patient developed a severe reduction (>=20%) in left
ventricular ejection fraction (LVEF) and only one patient developed
congestive heart failure (CHF). The total cumulative doxorubicin
equivalent exposure per treatment cycle for all 68 patients treated
with pixantrone is noted in the table below: Treatment Cycle No. of
Patients Pixantrone Lifetime Treatment Cumulative Cumulative Dose
Dose Median mg/m2 Median mg/m2 1 68 74 365.2 2 54 148 430.2 3 43
209 498.1 4 36 275 571.8 5 25 356 631.5 6 22 427 695.0 Lifetime
doses of doxorubicin of over 550 mg/m2 are associated with a high
incidence of CHF if the cumulative dose levels were solely with a
standard anthracycline. An additional new subgroup analysis was
highlighted by the ASCO discussant, which demonstrated the clinical
benefit associated with achieving a CR or CRu with pixantrone. On
an intent-to-treat basis, patients achieving a CR/CRu on the
pixantrone treatment arm (n=14) had a significant increase in the
duration of remission compared with the four patients who achieved
a CRu with standard chemotherapy (7 months vs. 3.5 months, p=0.03,
HR=0.279; a hazard ratio of less than one indicates a decreased
risk of disease progression and a p-value of less than 0.05
indicates statistical significance). An analysis was also reported
that evaluated the effect of prior rituximab therapy on response
rates. In the 38 patients who received pixantrone following prior
treatment with rituximab, 12 patients (32%) achieved a CR/CRu/PR of
which six patients (16%) achieved a CR/CRu. In the comparator arm,
the response rate was seven out of 39 patients (18%) with three
CRu. The discussant noted that overall response rates of 30% in
this population of patients would represent a significant advance
in the treatment of aggressive NHL and commented that that while
numerically higher, the overall incidence of cardiac events were
lower than expected in this patient group with substantial prior
doxorubicin exposure reflected by no significant change in ejection
fraction from baseline to end of treatment. "This data demonstrates
that pixantrone can induce durable complete remissions not only in
patients previously treated with standard front-line doxorubicin,
but even in patients who received an anthracycline as part of a
salvage regimen. Resistance to rituximab was not associated with
resistance to pixantrone. In patients with high cumulative prior
doxorubicin exposure, the frequency of severe cardiac toxicity
following up to six cycles of additional pixantrone was lower than
would be expected based on historical comparisons to studies of
doxorubicin," said James A. Bianco, M.D., Chief Executive Officer
of CTI. "We are pleased with these results as they underscore the
potential for pixantrone in this difficult to treat patient
population for whom few options exist." About the PIX301 EXTEND
Trial The PIX 301 EXTEND clinical trial was a phase III
single-agent trial of pixantrone for patients with relapsed or
refractory, aggressive NHL who received two or more prior therapies
and who were sensitive to treatment with anthracyclines. The trial
enrolled 140 patients and patients were randomized to receive
either pixantrone or another single-agent drug currently used for
the treatment of this patient population and selected by the
physician. CTI previously announced that its pivotal phase III
EXTEND (PIX 301) trial of pixantrone had achieved its primary
endpoint with patients randomized to treatment with pixantrone
achieving a significantly higher rate of confirmed (CR) and
unconfirmed complete remissions (CRu) compared to patients treated
with standard chemotherapy (14 out of 70 patients (20.0%) for the
pixantrone arm compared to four out of 70 patients (5.7%) for the
standard chemotherapy arm, p=0.02) with no patients in the standard
chemotherapy arm achieving a confirmed complete remission. The most
common grade 3, 4 adverse event observed on the pixantrone arm was
neutropenia in 41.2% of patients versus 19.4% on the comparator
arm. However, the incidence of grade 3, 4 febrile neutropenia was
only 7.4% versus 3.0% in the comparator arm. Grade 3, 4 infections
had a similar incidence in both study arms (18% vs. 13%). Although
the grade 3, 4 cardiac disorder was similar among the two treatment
groups (1.5% vs. 1.5%), there was a slightly higher incidence of
serious cardiac disorders in patients treated with pixantrone than
among patients who received comparator agents (8.8% vs. 4.5%).
Events considered cardiac disorders included cardiac arrest,
congestive heart failure, myocardial infarction, cyanosis,
pericardial effusion, and tachycardia. The ASCO poster is available
at http://www.celltherapeutics.com/investor_updates. In April 2009,
CTI began a rolling submission of a New Drug Application (the
"NDA") with the U.S. Food and Drug Administration (the "FDA") for
pixantrone to treat relapsed or refractory aggressive NHL. CTI
expects to complete the submission this month and will request
priority review, which if granted could lead to an approval
decision from the FDA in the fourth quarter of 2009. Pixantrone is
also now available in Europe on a named patient basis. About
Pixantrone Pixantrone (BBR 2778), is a novel major groove binder
with an aza-anthracenedione molecular structure that differentiates
it from the anthracyclines and other related chemotherapy agents.
Anthracyclines are the cornerstone therapeutic for the treatment of
lymphoma, leukemia, and breast cancer. Although they are
sufficiently effective to be used as first-line (initial)
treatment, they cause cumulative heart damage that may result in
congestive heart failure many years later. As a result, there is a
lifetime limit of anthracycline doses and most patients who
previously have been treated with an anthracycline are not able to
receive further anthracycline treatment if their disease returns.
It also can be administered through a peripheral vein rather than a
central implanted catheter as required for other drugs in this
class. 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.celltherapeutics.com/. Sign up for email alerts and get
RSS feeds at our Web site,
http://www.celltherapeutics.com/investors_news.htm 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 pixantrone to prove safe and effective (or
increase remission rates or progress free survival) for treatment
of relapsed or refractory aggressive NHL as determined by the FDA,
the possibility that the NDA submission will not be completed in
the second quarter of 2009, that priority review will not be
granted by the FDA and that a decision by the FDA is not rendered
in late 2009, CTI's ability to continue to raise capital as needed
to fund its operations, competitive factors, technological
developments, costs of developing, producing and selling
pixantrone, and the risk factors listed or described from time to
time in CTI's filings with the Securities and Exchange Commission
including, without limitation, CTI's most recent filings on Forms
10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not
intend 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 E:
http://www.celltherapeutics.com/press_room Investors Contact: Ed
Bell T: 206.282.7100 Lindsey Jesch T: 206.272.4347 F: 206.272.4434
E: http://www.celltherapeutics.com/investors Medical Information
Contact: T: 800.715.0944 E: DATASOURCE: Cell Therapeutics, Inc.
CONTACT: media, Dan Eramian, +1-206-272-4343, cell,
+1-206-854-1200, , or investors, Ed Bell, +1-206-282-7100, or
Lindsey Jesch, +1-206-272-4347, fax, +1-206-272-4434, , all of Cell
Therapeutics, Inc.; or Medical Information, 1-800-715-0944, Web
Site: http://www.celltherapeutics.com/
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