Pralatrexate vs Observation Following CHOP-based Chemotherapy in Undiagnosed Peripheral T-cell Lymphoma Patients

NCT01420679 | Terminated Phase 3 Results DMC

• 2 other identifiers: PDX-0172010-022230-81
• Study Type: interventional
• Target: 21
• Locations: 13 countries
• Sites: 55

Brief Summary

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.

Conditions

Peripheral T-cell Lymphoma

Keywords

Lymphoproliferative Disorders; Lymphoma; Non-Hodgkin's Lymphoma; T-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS)

  PFS was defined as the time in days from randomization to the date of objective documentation of progressive disease (PD) or death, regardless of cause (date of PD or death - date of randomization + 1). PFS was to be assessed according to the International Workshop Criteria (IWC) without including positron emission tomography (PET). PD was defined as any new lesion or increase by greater than or equal to (\>=) 50 percent (%) of previously involved sites from nadir. Participants who were alive without a disease response assessment of PD was to be censored at their last disease assessment date or the date of randomization, whichever was later. Date of progression was not to be imputed for participants with missing tumor assessments before an assessment of PD. Participants who withdraw from treatment prior to PD were to be followed for disease status whenever possible. Participants who have no response assessments after baseline were to be censored at randomization.

  From randomization to the date of progression of disease or death due to any cause (up to 76 months)

• Overall Survival (OS)

  Overall survival was defined as the time in days from randomization to the date of death, regardless of cause (date of death - date of randomization + 1).

  From randomization until death (up to 76 months)

Secondary Outcomes (2)

• Objective Response Rate

  Up to 2 years

• Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities

  From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years)

Study Arms (2)

Pralatrexate

EXPERIMENTAL

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

Observation

NO INTERVENTION

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.

Interventions

Pralatrexate Injection DRUG

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.

Also known as: FOLOTYN, PDX, Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin

Pralatrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Spectrum Pharmaceuticals, Inc: lead

Study Sites (55)

Detroit Clinical Research Center, PC

Novi, Michigan, 48377, United States

Location

New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Center

Bedford Park, South Australia, 5042, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7001, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Saint Vincent's Hospital Melbourne

Fitzroy, Victoria, 3109, Australia

Location

Frankston Hospital

Frankston, Victoria, 3199, Australia

Location

Cabrini Health

Malvern, Victoria, 3144, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

AZ Sint-Jan

Bruges, 8000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Sunnybrook Health Science Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, H4J 1C5, Canada

Location

Hôpital Morvan

Brest, 29609, France

Location

CHU Haut-Leveque

Pessac, 33604, France

Location

St James Hospital

Dublin, Ireland

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Hadassah Ein-Kerem Medical Centre

Jerusalem, 91120, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli, 47014, Italy

Location

Az. Ospedaliera Universitaria S. Orsola Malpighi

Bologna, 40138, Italy

Location

Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Ospedale S. Maria delle Croci

Ravenna, 48121, Italy

Location

Università Cattolica del Sacro Cuore

Roma, 00168, Italy

Location

Az. Ospedaliera Università Senese

Siena, 53100, Italy

Location

Middlemore Hospital

Otahuhu, Auckland, 1640, New Zealand

Location

Auckland City Hospital / Auckland University

Auckland, 1010, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

North Shore Hospital

Milford, New Zealand

Location

Klinika Nowotworów Ukladu Chlonnego Centrum Onkologii Instytut Marii Sklodowskiej-Curie

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Dept of Hematology and Transplantology

Gdansk, 80-952, Poland

Location

Małopolskie Centrum Medyczne

Krakow, 30-510, Poland

Location

Auxilio Mutuo Cancer Center

San Juan, 00918, Puerto Rico

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Complejo Hospitalario de Navarra, Servicio de Hematologia

Pamplona, Navarre, 31008, Spain

Location

Complejo Hospitalario Universitario A Coruña- Hospital A Coruña

A Coruña, 15006, Spain

Location

Hospital General Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital de Madrid Norte-Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, 28222, Spain

Location

Royal Cornwall Hospital

Truro, Cornwall, TR1 3LJ, United Kingdom

Location

Poole Hospital NHS Foundation Trust, Poole General Hospital

Poole, Dorset, BH15 2JB, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL68DH, United Kingdom

Location

Sandwell & West Birmingham Hospitals NHS Trust

West Bromwich, England, B71 4HJ, United Kingdom

Location

Antrim Area Hospital

Antrim, Northern Ireland, BT41 2RL, United Kingdom

Location

NHS Greater Glasgow and Clyde Western Infirmary

Glasgow, Scotland, G11 6NT, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Velindre Hospital

Cardiff, CF14 2TL, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Mount Vernon Cancer Centre

Middlesex, HA6 2RN, United Kingdom

Location

UHCW (University Hospital Coventry and Warwickshire)

Warwick, CA34 5BW, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Lymphoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell

Interventions

10-propargyl-10-deazaaminopterin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The study was prematurely terminated due to business reasons. There were no safety concerns that led to study closure. No efficacy assessments and analysis was conducted. A full statistical analysis and report were not completed.

Results Point of Contact

• Title: Gajanan Bhat
• Organization: Spectrum Pharmaceuticals, Inc

gajanan.Bhat@sppirx.com

949-743-9219

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2011
• First Posted: August 22, 2011
• Study Start: August 1, 2011
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: November 19, 2021
• Results First Posted: November 19, 2021

Record last verified: 2021-11

Locations

FR (2); IL (4); NZ (4); BE (2); PR (1); PL (3); US (3); AU (8); CA (2); ES (8); IE (1); IT (6); GB (11)