Healthcare Industry News: peripheral T-cell lymphoma
News Release - August 17, 2011
Allos Therapeutics Initiates Phase 3 Registration Trial of FOLOTYN(R) in Newly Diagnosed Patients with Peripheral T-Cell Lymphoma Following Treatment with a CHOP-based RegimenFirst patient enrolled following SPA agreement with FDA on design of PDX-017
WESTMINSTER, Colo.--(Healthcare Sales & Marketing Network)-- Allos Therapeutics, Inc. (NASDAQ:ALTH ) today announced the enrollment of the first patient in a Phase 3 randomized clinical trial (PDX-017) evaluating FOLOTYN® (pralatrexate injection) in patients with previously undiagnosed peripheral T-cell lymphoma (PTCL). This study is open to enroll newly diagnosed patients with PTCL who have achieved an objective response following initial treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or a CHOP-like regimen. Earlier this year, Allos reached agreement with the U.S. Food and Drug Administration (FDA) under its Special Protocol Assessment (SPA) process on the design of this Phase 3 trial. The SPA provides FDA agreement that the study design and planned analysis of this Phase 3 trial adequately address the objectives necessary to support a regulatory submission. FOLOTYN, a folate analogue metabolic inhibitor, is approved in the U.S. for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).
“We are pleased to be initiating this Phase 3 trial, which has the potential to expand the clinical utility of FOLOTYN into the first-line treatment setting,” said Charles Morris, MB ChB, MRCP, chief medical officer at Allos Therapeutics. “CHOP and CHOP-based treatments are the most commonly used therapeutic regimens for patients with newly diagnosed PTCL; however, a majority of these patients progress or relapse following CHOP. This Phase 3 study will explore the potential for FOLOTYN to improve outcomes for these patients.”
FOLOTYN was approved for the treatment of patients with relapsed or refractory PTCL in the United States under the FDA's accelerated approval program, which allows the FDA to approve products for cancer or other life-threatening diseases based on initial positive clinical data. As a condition of approval, Allos is required to conduct post-approval studies that are intended to verify and describe the clinical benefit of FOLOTYN in patients with T-cell lymphomas and assess whether FOLOTYN poses a serious risk of altered drug levels resulting from organ impairment. The Phase 3 study of FOLOTYN in newly diagnosed patients with PTCL following initial treatment with CHOP or a CHOP-like regimen is one of the Company’s post-marketing requirements. If successful, the data are intended to support an expanded indication for FOLOTYN in the United States in this patient population and to convert the current accelerated approval for relapsed and/or refractory PTCL to a full approval. The data are also intended to support global regulatory submissions for FOLOTYN for this patient population outside the United States.
Phase 3 Trial Design
PDX-017 is a randomized, open-label, multi-center, international Phase 3 study that will seek to enroll 549 patients in more than 30 countries. The study will seek to establish the safety and efficacy of sequential FOLOTYN versus observation in patients with previously undiagnosed PTCL who have achieved an objective response following initial treatment with CHOP or a CHOP-like regimen.
The co-primary endpoints of the trial will be progression-free survival (PFS) and overall survival (OS). Patients will be randomized in a 2 to 1 ratio to receive either FOLOTYN or to remain under observation following their initial treatment with CHOP or a CHOP-like regimen. The initial dose of FOLOTYN will be 30mg/m2 administered 3 out of every 4 weeks, with dose reductions allowed for defined toxicity.
For more information regarding this trial, refer to www.clinicaltrials.gov.
About peripheral T-cell lymphoma
peripheral T-cell lymphomas are a biologically diverse group of aggressive, mature T and NK (natural killer) cell non-Hodgkin lymphomas with similar outcomes, which include PTCL-NOS (PTCL not otherwise specified), AITL (angioimmunoblastic T-cell lymphoma), and ALCL (anaplastic large-cell lymphoma).1 The prognosis for patients with PTCL is generally poor for most subtypes.2
T-cell lymphomas account for approximately 10% to 15% of all cases of non-Hodgkin lymphomas (NHL).1-3 Allos estimates the current annual incidence of PTCL to be approximately 5,900 patients in the U.S. and approximately 6,000-7,000 patients in the top five European markets. The majority of patients ultimately have refractory disease to a variety of agents, including multi-agent chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens. The 5-year overall survival rate in these patients is 25% to 40%, depending on sub-type.4-5
FOLOTYN, a folate analogue metabolic inhibitor, was discovered by Sloan-Kettering Institute for Cancer Research, SRI International and Southern Research Institute and developed by Allos Therapeutics. In May 2011, the Company entered into a strategic collaboration agreement with Mundipharma International Corporation Limited (Mundipharma) to co-develop FOLOTYN globally. Under the agreement, Allos retains full commercialization rights for FOLOTYN in the United States and Canada, with Mundipharma having exclusive rights to commercialize FOLOTYN in all other countries.
In September 2009, the FDA granted accelerated approval for FOLOTYN for use as a single agent for the treatment of patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression free survival or overall survival has not been demonstrated. FOLOTYN has been available to patients in the U.S. since October 2009. An updated analysis of data from the pivotal PROPEL trial, which supported the FDA’s accelerated approval, was published in the March 20, 2011 issue of the Journal of Clinical Oncology. Allos and Mundipharma are currently pursuing regulatory approval to market FOLOTYN in the European Union for relapsed or refractory PTCL and are developing FOLOTYN in other potential indications. Allos’ MAA was accepted for review by the EMA in December 2010.
About Allos Therapeutics
Allos Therapeutics, Inc. (Nasdaq:ALTH ) is a biopharmaceutical company committed to the development and commercialization of innovative anti-cancer therapeutics. On July 20, 2011, Allos announced that it had entered into a definitive merger agreement with AMAG Pharmaceuticals, Inc. The transaction is subject to approval by both companies’ stockholders and other customary closing conditions. Allos is currently focused on the development and commercialization of FOLOTYN® (pralatrexate injection), a folate analogue metabolic inhibitor. FOLOTYN is approved in the U.S. for the treatment of patients with relapsed or refractory PTCL. Allos is also developing FOLOTYN in other hematologic malignancies and solid tumors. For additional information, please visit www.allos.com.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
FOLOTYN may suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anemia. Monitor blood counts and omit or modify dose for hematologic toxicities.
Mucositis may occur. If =Grade 2 mucositis is observed, omit or modify dose. Patients should be instructed to take folic acid and receive vitamin B12 to potentially reduce treatment-related hematological toxicity and mucositis.
Fatal dermatologic reactions may occur. Dermatologic reactions may be progressive and increase in severity with further treatment. Patients with dermatologic reactions should be monitored closely, and if severe, FOLOTYN should be withheld or discontinued.
Tumor lysis syndrome may occur. Monitor patients and treat if needed.
FOLOTYN can cause fetal harm. Women should avoid becoming pregnant while being treated with FOLOTYN and pregnant women should be informed of the potential harm to the fetus.
Use caution and monitor patients when administering FOLOTYN to patients with moderate to severe renal function impairment.
Elevated liver function test abnormalities may occur and require monitoring. If liver function test abnormalities are =Grade 3, omit or modify dose.
The most common adverse reactions were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events are pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia.
Use in Specific Patient Population
Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.
Co-administration of drugs subject to renal clearance (e.g., probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal clearance.
Please see FOLOTYN Full Prescribing Information at www.FOLOTYN.com.
Safe Harbor Statement
This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding the potential future development of FOLOTYN for the treatment of patients with peripheral T-cell lymphoma or any other type of cancer and other statements that are other than statements of historical facts. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “expects,” “intends,” “plans,” anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” “continue,” and other similar terminology or the negative of these terms, but their absence does not mean that a particular statement is not forward-looking. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties include, among others: that the pace of subject enrollment in the planned Phase 3 trial may be slower than expected, that the Phase 3 trial does not successfully meet safety and efficacy endpoints or that the data from the trial does not support continued marketing of FOLOTYN, and the risk that the Company may lack the financial resources and access to capital to fund future clinical trials for FOLOTYN. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2011, and in the Company's other periodic reports and filings with the Securities and Exchange Commission. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. All forward-looking statements are based on information currently available to the Company on the date hereof, and the Company undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this presentation, except as required by law.
Note: The Allos logo and FOLOTYN name are trademarks of Allos Therapeutics, Inc.
1. The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood. 1997;89(11):3909-3908.
2. Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update [review]. Lancet Oncol. 2004;5(6):341-353.
3. O'Leary HM, Savage KJ. Novel therapies in peripheral T-cell lymphomas [review]. Curr Oncol Rep. 2008;134(5):202-207.
4. Savage KJ, Chhanabhai M, Gascoyne RD, et al. Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification. Ann Oncol 2004;15(10):1467-75.
5. Savage KJ. peripheral T-cell lymphomas. Blood Rev. 2007; 21:201-216.
Source: Allos Therapeutics
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