Study of Pralatrexate Versus Observation Following CHOP-based Chemotherapy in Previously Undiagnosed Peripheral T-cell Lymphoma Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Spectrum Pharmaceuticals, Inc
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01420679
First received: August 18, 2011
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to see if pralatrexate extends response and survival following CHOP-based chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) and if pralatrexate improves response in patients with partial response following CHOP-based chemotherapy. Patients will either receive pralatrexate or be under observation. All patients will receive vitamins B12 and folic acid and attend regular clinic visits to evaluate their disease and health.


Condition Intervention Phase
Peripheral T-cell Lymphoma
Drug: Pralatrexate Injection
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Phase 3 Study of Sequential Pralatrexate Versus Observation in Patients With Previously Undiagnosed Peripheral T-cell Lymphoma Who Have Achieved an Objective Response Following Initial Treatment With CHOP-based Chemotherapy

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: Assessed at 8 weeks (+/-1 wk) then every 12 weeks (+/-1 wk) through 3 years, then every 24 weeks (+/-4 wks) until progression of disease (PD) or up to 7 years post-randomization ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Collected approximately every 6 months after documented PD through 7 years post-randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective Response to Pralatrexate versus Observation [ Time Frame: Assessed at 8 weeks (+/-1 wk) then every 12 weeks (+/-1 wk) through 3 years, then every 24 weeks (+/-4 wks) until progression of disease (PD) or up to 7 years post-randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 549
Study Start Date: August 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pralatrexate
Patients randomized to the Pralatrexate Arm will receive pralatrexate injection and Vitamins B12 and Folic Acid until a criterion for pralatrexate injection treatment discontinuation is met.
Drug: Pralatrexate Injection

Intravenous (IV) push administration over 30 seconds to 5 minutes via a patent IV line containing normal saline (0.9% sodium chloride).

Initial dose: 30 mg/m2

Administered weekly for 3 weeks of a 4-week cycle until criteria for discontinuation per the protocol are met.

Other Names:
  • FOLOTYN
  • PDX
  • Pralatrexate
  • (RS)-10-propargyl-10-deazaaminopterin
No Intervention: Observation
Patients randomized to the Observation Arm will receive Vitamins B12 and Folic Acid and remain under observation until a criterion for observation discontinuation is met.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has one of the following peripheral T-cell lymphoma (PTCL) subtypes confirmed by an independent central pathology reviewer, using the Revised European American Lymphoma World Health Organization disease classification:

    • T/natural killer (NK)-cell leukemia/lymphoma
    • Adult T-cell lymphoma (TCL)/leukemia (human T-cell leukemia virus 1+)
    • Angioimmunoblastic TCL
    • Anaplastic large cell lymphoma (ALCL), primary systemic type, excluding anaplastic lymphoma kinase positive (ALK+) with International Prognostic Index (IPI) score less than 2 at initial diagnosis and complete response (CR) after CHOP-based therapy
    • PTCL-unspecified
    • Enteropathy-type intestinal lymphoma
    • Hepatosplenic TCL
    • Subcutaneous panniculitis TCL
    • Transformed mycosis fungoides (tMF)
    • Extranodal T/NK-cell lymphoma nasal or nasal type
    • Primary cutaneous gamma-delta TCL
    • Primary cutaneous CD8+ aggressive epidermic cytotoxic TCL
  • Documented completion of at least 6 cycles of CHOP-based therapy:

    • CHOP 21
    • CHOP 14
    • CHOP + etoposide
    • Other CHOP variants: substitution allowed for 1 component with a drug of the same mechanism of action. Additional components, except alemtuzumab, are allowed. Rituximab may be added if not given within 3 cycles of randomization.
  • Patient has achieved CR or partial response (PR) per per investigator's assessment following completion of CHOP-based therapy and has had radiological assessment within 21 days prior to randomization.
  • Eastern Cooperative Oncology Group performance status less than or equal to 2.
  • Adequate blood, liver, and kidney function as defined by laboratory tests.
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization and agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate.
  • Men who are sexually active, including those with a pregnant partner, must agree to practice a medically acceptable barrier method contraceptive regimen (eg, condoms) while receiving pralatrexate and for 90 days after the last administration of pralatrexate.
  • Has given written informed consent.

Exclusion Criteria:

  • Patient has:

    • Precursor T/NK neoplasms
    • ALCL (ALK+) with IPI score less than 2 at initial diagnosis and CR after CHOP-based therapy
    • T cell prolymphocytic leukemia
    • T cell large granular lymphocytic leukemia
    • Mycosis fungoides, except tMF
    • Sézary syndrome
    • Primary cutaneous CD30+ disorders: ALCL and lymphomatoid papulosis
  • If there is a history of prior malignancies other than those below, must be disease free for at least 5 years. Patients with malignancies listed below less than 5 years before study entry may be enrolled if they have received treatment resulting in complete resolution of the cancer and have no clinical, radiologic, or laboratory evidence of active/recurrent disease.

    • non-melanoma skin cancer
    • carcinoma in situ of the cervix
    • localized prostate cancer
    • localized thyroid cancer
  • Receipt of prior chemotherapy (CT) or radiation therapy (RT) for PTCL, other than a single allowed CHOP regimen, except:

    • Patients with nasal NK lymphoma who received local RT less than 4 weeks prior to randomization.
    • Patients with tMF who received 1 systemic single-agent CT (except methotrexate) prior to transformation.
  • Prior exposure to pralatrexate.
  • Receipt of systemic corticosteroids within 3 weeks of study treatment, unless patient has been taking a continuous dose of 10 mg/day or less of oral prednisone or equivalent for at least 4 weeks or as part of a CHOP prednisone taper.
  • Planned use of any treatment for PTCL during the course of the study.
  • Patient has:

    • Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of less than 100 mm3 or detectable viral load within past 3 months and receiving anti-retroviral therapy.
    • Hepatitis B (HBV)-positive serology and is receiving interferon therapy or has liver function test results outside the parameters of study inclusion criteria. Other antiviral therapies are permitted if at a stable dose for at least 4 weeks.
    • Hepatitis C (HCV) virus with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy.
    • Symptomatic central nervous system metastases or lesions requiring treatment.
    • Uncontrolled hypertension or congestive heart failure Class III/IV per the New York Heart Association's Heart Failure Guidelines
    • Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness impairing the ability of the patient to receive protocol treatment.
  • Major surgery within 2 weeks prior to study entry, except for line placement or biopsy procedure.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01420679

Contacts
Contact: Sue Yancik 720-560-2198 Sue.Yancik@sppirx.com

  Hide Study Locations
Locations
United States, Georgia
Georgia Health Sciences University Withdrawn
Augusta, Georgia, United States, 30912-3125
United States, Michigan
Detroit Clinical Research Center, PC Recruiting
Novi, Michigan, United States, 48377
Contact: Candice Shallal       candice.shallal@dcrc.us   
Principal Investigator: Craig Gordon, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Steven Horwitz, MD    212-639-3045      
Principal Investigator: Steven Horwitz, MD         
New York Presbyterian Hospital Recruiting
New York, New York, United States, 10021
Contact: Arcania Garcia       arg2006@med.cornell.edu   
Principal Investigator: Jia Ruan, MD         
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Mengiun Zhu    +61 8 8222 336    mengjun.zhu@health.sa.gov.au   
Principal Investigator: Ian Lewis         
Flinders Medical Center Recruiting
Bedford Park, South Australia, Australia, 5042
Contact: Kayleen Charles    +61 8 8204 5453    kayleen.charles@health.sa.gov.au   
Principal Investigator: Bryone Kuss, MD         
Australia, Tasmania
Royal Hobart Hospital Recruiting
Hobart, Tasmania, Australia, 7001
Contact: Sue Davoren    +61 3 6222 8120    sue.davoren@dhhs.tas.gov.au   
Principal Investigator: Anna Johnston, MD         
Australia, Victoria
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
Contact: Matthew VanDam    +44 3 9594 4044    Matthew.VanDam@southernhealth.org.au   
Principal Investigator: Stephen Opat, MD         
Saint Vincent's Hospital Melbourne Recruiting
Fitzroy, Victoria, Australia, 3109
Contact: Lisa Demosthenous    61 3 9288 3182    lisa.demosthenous@svhm.org.au   
Principal Investigator: Constantine Tam, MD         
Principal Investigator: Robin Filshie, MD         
Frankston Hospital Recruiting
Frankston, Victoria, Australia, 3199
Contact: Theresa de Man    +03 9784-7209      
Principal Investigator: John Catalano, MD         
Cabrini Health Recruiting
Malvern, Victoria, Australia, 3144
Contact: Mary Lane    +61 3 95-8 1669    mlane@cabrini.com.au   
Principal Investigator: H. Miles Prince         
Australia, Western Australia
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia, 6000
Principal Investigator: Paul Cannell, MD         
Belgium
AZ Sint-Jan Recruiting
Brugge, Belgium, 8000
Contact: Annelies Sneppe    32 5045 2328    annelies.sneppe@azsintjan.be   
Principal Investigator: Achiel Van Hoof, MD         
Universitair Ziekenhuis Gent Recruiting
Gent, Belgium, 9000
Contact: Sofie Lust    +32 93320870    sofie.lust@uzgent.be   
Principal Investigator: Fritz Offner, MD         
Canada, Ontario
Sunnybrook Health Science Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Claudia Li    416-480-5000 ext 7937    claudia.li@sunnybrook.ca   
Principal Investigator: Matthew Cheung, MD         
Canada, Quebec
Hôpital du Sacré-Coeur de Montréal Recruiting
Montreal, Quebec, Canada, H4J 1C5
Contact: Caroline Chagnon    514 338-2222 ext 2816    Caroline.chagnon@crhsc.rtss.qc.ca   
Principal Investigator: Inès Chamakhi, MD         
France
Hôpital Morvan Recruiting
Brest, France, 29609
Contact: Dominique Gillet    +33 2 98 22 32 45    dominique.gillet@chu-brest.fr   
Principal Investigator: Adrian Tempescul, MD         
CHU Haut-Leveque Recruiting
Pessac, France, 33604
Contact: Frederic Perry    33(0)557656511    frederic.perry@chu-bordeaux.fr   
Principal Investigator: Kamal Bouabdallah, MD         
Ireland
St James Hospital Recruiting
Dublin 8, Ireland
Contact: Cliona Grant         
Principal Investigator: Cliona Grant         
Israel
Shaare Zedek Medical Center Recruiting
Jerusalem, Israel, 91031
Contact: Jenia Berelovich    972-2-6666448    jeniaber@szmc.org.il   
Principal Investigator: Rosa Ruchlemer, MD         
Hadassah Ein-Kerem Medical Centre Recruiting
Jerusalem, Israel, 91120
Contact: Dorit Cohen    972-2-6779267    sdorit@hadassah.org.il   
Principal Investigator: Dina Ben Yehuda, MD         
Rabin Medical Center Recruiting
Petach Tikva, Israel, 49100
Contact: Sara Gechler    +972-3-9378078    sarage1@clalit.org.il   
Principal Investigator: Ofer Shpilberg, MD         
Principal Investigator: Ronit Gurion         
Chaim Sheba Medical Center Recruiting
Tel Hashomer, Israel, 52621
Contact    +36 30 6455788      
Principal Investigator: Arnon Nagler, MD         
Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Recruiting
Meldola, Forli, Italy, 47014
Contact: Francesca Fabbri    +39 0543 739281    francesca.fabbri@irst.it   
Principal Investigator: Pier Paolo Fattori, MD         
Az. Ospedaliera Universitaria S. Orsola Malpighi Recruiting
Bologna, Italy, 40138
Contact: Lisa Argnani    +39 051 6363227    lisa.argnani@unibo.it   
Principal Investigator: Pier Luigi Zinzani, Prof         
Spedali Civili di Brescia Recruiting
Brescia, Italy, 25123
Contact: Marta Petullà    39 030 3996269    marta-petulla@hotmail.it   
Principal Investigator: Giuseppe Rossi, MD         
Ospedale S. Maria delle Croci Recruiting
Ravenna, Italy, 48121
Contact: Bernadette Vertogen    +39 0544286223    b.vertogen@ausl.ra.it   
Principal Investigator: Alfonso Zaccaria, MD         
Principal Investigator: Monica Tani         
Università Cattolica del Sacro Cuore Recruiting
Roma, Italy, 00168
Contact: Dr. Francesco D'Aol         
Principal Investigator: Giuseppe Leone, MD         
Principal Investigator: Dr. Francesco D'Alo         
Az. Ospedaliera Università Senese Recruiting
Siena, Italy, 53100
Contact: Dr. Cristiana Cafarelli    39 0577 586718    cafarelli@unisi.it   
Principal Investigator: Alberto Fabbri, MD         
New Zealand
Middlemore Hospital Recruiting
Otahuhu, Auckland, New Zealand, 1640
Contact: Yvonne Dunn    +64 9276 0044 ext 2969    yvonne.dunn@ccrep.org.nz   
Principal Investigator: Samma Issa, MD         
Auckland City Hospital / Auckland University Recruiting
Auckland, New Zealand, 1010
Contact: Fay Sommerville    64 9 9239807    f.sommerville@auckland.ac.nz   
Principal Investigator: Leanne Berkahn, MD         
Christchurch Hospital Recruiting
Christchurch, New Zealand, 8011
Contact: Jo Sanders    +64 3 3640 377    joanne.sanders@cdhb.health.nz   
Principal Investigator: Andrew Butler, MD         
North Shore Hospital Recruiting
Milford, New Zealand
Contact: Vivienne King    09 4868920 ext 3379    vivienne.king@waitematadhb.govt.nz   
Principal Investigator: David Simpson, MD         
Poland
Klinika Nowotworów Ukladu Chlonnego Centrum Onkologii Instytut Marii Sklodowskiej-Curie Recruiting
Warszawa, Mazowieckie, Poland, 02-781
Contact: Anna Dabrowska-Iwanicka, MD    48 22 5462618    adab@col.waw.pl   
Principal Investigator: Jan Walewski, MD         
Dept of Hematology and Transplantology Recruiting
Gdansk, Poland, 80-952
Contact: Dr. Wanda Knopinska-Posluszny    48 58 3492230    wandak@gumed.edu.pl   
Principal Investigator: Andrzej Hellman, MD         
Małopolskie Centrum Medyczne Recruiting
Kraków, Poland, 30-510
Contact: Dr Małgorzata Kilian    48122954134    mcm.mcm.malgorzata.kilian@mp.pl   
Principal Investigator: Wojciech Jurczak, MD         
Puerto Rico
Auxilio Mutuo Cancer Center Recruiting
San Juan, Puerto Rico, 00918
Contact: Idalia Liboy, MD    787-758-2000 ext 3569    iliboy@auxiliomutuo.com   
Principal Investigator: Fernando Cabanillas, MD         
Spain
Complejo Hospitalario de Navarra, Servicio de Hematologia Recruiting
Pamplona, Navarra, Spain, 31008
Contact: Paloma Millan-Palanca    0034848428428    paloma.millan.palanca@navarra.es   
Principal Investigator: Mercede R. Calvillo         
Clinica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Contact: Celia Roncal    0034 948296397    croncal@unav.es   
Principal Investigator: Jose Juan Rifon Roca         
Complejo Hospitalario Universitario A Coruña- Hospital A Coruña Recruiting
A Coruña, Spain, 15006
Contact: Guillermo Deben         
Principal Investigator: Guillermo Deben         
Hospital Clínic i Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Antonio de la Riva    34 932279214    delariva@clinic.ub.es   
Principal Investigator: Eva Giné Soca, MD         
Hospital General Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Oriol Olivé Noguer    +34 93 489 43 75    oolive@vhebron.net   
Principal Investigator: Andrés López Hernández         
Hospital de Madrid Norte-Sanchinarro Recruiting
Madrid, Spain, 28050
Contact: Tamara Garcia Lopez    +34917567800    tgarcia@hmhospitales.com   
Principal Investigator: Jaime Pérez De Oteyza, MD         
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain, 28034
Contact: Olga Fernandez    34 91 336 86 86    fc_olg@hotmail.com   
Principal Investigator: Maria Calbacho Robles         
Hospital Universitario Puerta de Hierro Majadahonda Recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Ana Garranzo    +34 91 191 79 13    agarranzo@idiphim.org   
Principal Investigator: José García Marco, MD         
United Kingdom
Royal Cornwall Hospital Recruiting
Truro, Cornwall, United Kingdom, TR1 3LJ
Contact: Bianca Mills    01872 252527    bianca.mills@rcht.cornwall.nhs.uk   
Principal Investigator: Anton Kruger         
Poole Hospital NHS Foundation Trust, Poole General Hospital Recruiting
Poole, Dorset, United Kingdom, BH15 2JB
Contact: Kate Mutendera    01202 442633    Kate.mutendera@poole.nhs.uk   
Principal Investigator: Fergus Jack         
Derriford Hospital Recruiting
Devon, England, United Kingdom, PL68DH
Contact: Nicola Crosbie    +44 1752 431 043    nicola.crosbie@nhs.net   
Principal Investigator: Simon Rule, MD         
Sandwell & West Birmingham Hospitals NHS Trust Recruiting
West Bromwich, England, United Kingdom, B71 4HJ
Contact: Jackie Martin       jackie.martin2@nhs.net   
Principal Investigator: Farooq Wandroo, MD         
Antrim Area Hospital Recruiting
County Antrim, Northern Ireland, United Kingdom, BT41 2RL
Contact: Kirsty Mckay, RN    44 02894424000    Kirsty.McKay@northerntrust.hscni.net   
Principal Investigator: Scott McCloskey         
NHS Greater Glasgow and Clyde Western Infirmary Recruiting
Glasgow, Scotland, United Kingdom, G11 6NT
Contact: Louise Dinnett       Louise.Dinnett@glasgow.ac.uk   
Principal Investigator: Pam McKay, MD         
Belfast City Hospital Recruiting
Belfast, United Kingdom, BT9 7AB
Contact: Lorraine McKenna    +44289032924100    lorrainem.mckenna@belfasttrus.hsnci.net   
Principal Investigator: Paul Kettle, MD         
Velindre Hospital Recruiting
Cardiff, United Kingdom, CF14 2TL
Contact: Amanda Jackson    +44 2920815888    amanda.jackson2@wales.nhs.uk   
Principal Investigator: Eve Gallop-Evans, MD         
Royal Liverpool University Hospital Recruiting
Liverpool, United Kingdom, L7 8XP
Contact: Tracey Wellman    +44 151 70 6 4889    tracey.wellman@rlbuht.nsh.uk   
Principal Investigator: Nagesh Kalakonda, MD         
Mount Vernon Cancer Centre Recruiting
Middlesex, United Kingdom, HA6 2RN
Contact: Charina O'Campo       charina.ocampo@nhs.net   
Principal Investigator: Peter Hoskin, MD         
UHCW (University Hospital Coventry and Warwickshire) Recruiting
Warwick, United Kingdom, CA34 5BW
Contact: Kimberly White    +44 2476 967151    kimberley.white@uhcw.nhs.uk   
Principal Investigator: Anton Borg, MD         
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Study Director: Pankaj Sharma, MD Spectrum Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01420679     History of Changes
Other Study ID Numbers: PDX-017, 2010-022230-81
Study First Received: August 18, 2011
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Italy: Ethics Committee
Israel: Ethics Commission
New Zealand: Medsafe
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Spectrum Pharmaceuticals, Inc:
Lymphoproliferative Disorders
Lymphoma
Non-Hodgkin's Lymphoma
T-cell Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
10-deazaaminopterin
Aminopterin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014