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

NCT ID: NCT01420679

Last Updated: 2021-11-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2017-12-31

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.

Detailed Description

This was an international, multi-center, randomized, Phase 3, open-label study of sequential pralatrexate versus observation in patients with previously undiagnosed PTCL who have achieved an objective response following initial treatment with CHOP-based chemotherapy.

Upon documentation of completion of an objective response following at least 6 cycles of a designated CHOP-based chemotherapy confirmation of histopathology by independent review, and confirmation that all eligibility criteria were met, patients were randomized in a 2:1 ratio to either pralatrexate or observation, according to a permuted block design with stratification factor of Tumor Response per Investigator at completion of CHOP-based therapy (Complete Response [CR] vs Partial Response [PR]).

All patients who receive at least 1 dose of pralatrexate were followed for safety through 35 (± 5) days after their last dose of pralatrexate or until all treatment-related AEs have resolved or returned to baseline/Grade 1, whichever is longer, or until it was determined that the outcome does not change with further follow-up.

Conditions

Peripheral T-cell Lymphoma

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pralatrexate Injection

Intervention Type: 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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

FOLOTYN; PDX; Pralatrexate; (RS)-10-propargyl-10-deazaaminopterin

Eligibility 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.

• 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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Detroit Clinical Research Center, PC

Novi, Michigan, United States

New York Presbyterian Hospital

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Flinders Medical Center

Bedford Park, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Saint Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Frankston Hospital

Frankston, Victoria, Australia

Cabrini Health

Malvern, Victoria, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

AZ Sint-Jan

Bruges, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Hôpital du Sacré-Coeur de Montréal

Montreal, Quebec, Canada

Hôpital Morvan

Brest, , France

CHU Haut-Leveque

Pessac, , France

St James Hospital

Dublin, , Ireland

Shaare Zedek Medical Center

Jerusalem, , Israel

Hadassah Ein-Kerem Medical Centre

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli, Italy

Az. Ospedaliera Universitaria S. Orsola Malpighi

Bologna, , Italy

Spedali Civili di Brescia

Brescia, , Italy

Ospedale S. Maria delle Croci

Ravenna, , Italy

Università Cattolica del Sacro Cuore

Roma, , Italy

Az. Ospedaliera Università Senese

Siena, , Italy

Middlemore Hospital

Otahuhu, Auckland, New Zealand

Auckland City Hospital / Auckland University

Auckland, , New Zealand

Christchurch Hospital

Christchurch, , New Zealand

North Shore Hospital

Milford, , New Zealand

Klinika Nowotworów Ukladu Chlonnego Centrum Onkologii Instytut Marii Sklodowskiej-Curie

Warsaw, Masovian Voivodeship, Poland

Dept of Hematology and Transplantology

Gdansk, , Poland

Małopolskie Centrum Medyczne

Krakow, , Poland

Auxilio Mutuo Cancer Center

San Juan, , Puerto Rico

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Complejo Hospitalario de Navarra, Servicio de Hematologia

Pamplona, Navarre, Spain

Complejo Hospitalario Universitario A Coruña- Hospital A Coruña

A Coruña, , Spain

Hospital General Vall d'Hebron

Barcelona, , Spain

Hospital Clínic i Provincial de Barcelona

Barcelona, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital de Madrid Norte-Sanchinarro

Madrid, , Spain

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, , Spain

Royal Cornwall Hospital

Truro, Cornwall, United Kingdom

Poole Hospital NHS Foundation Trust, Poole General Hospital

Poole, Dorset, United Kingdom

Derriford Hospital

Plymouth, England, United Kingdom

Sandwell & West Birmingham Hospitals NHS Trust

West Bromwich, England, United Kingdom

Antrim Area Hospital

Antrim, Northern Ireland, United Kingdom

NHS Greater Glasgow and Clyde Western Infirmary

Glasgow, Scotland, United Kingdom

Belfast City Hospital

Belfast, , United Kingdom

Velindre Hospital

Cardiff, , United Kingdom

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Mount Vernon Cancer Centre

Middlesex, , United Kingdom

UHCW (University Hospital Coventry and Warwickshire)

Warwick, , United Kingdom

Countries

Austria; Brazil; Bulgaria; Chile; Colombia; Czechia; Germany; Hong Kong; Hungary; Mexico; Peru; Romania; Russia; Singapore; South Korea; Taiwan; Ukraine; United States; Australia; Belgium; Canada; France; Ireland; Israel; Italy; New Zealand; Poland; Puerto Rico; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2010-022230-81

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PDX-017

Identifier Type: -

Identifier Source: org_study_id