Clinical trial NCT01420679: Pralatrexate vs Observation Following CHOP-based Chemotherapy in Undiagnosed Peripheral T-cell Lymphoma Patients
Official title: A Multi-center, Randomized, Phase 3 Study of Sequential Pralatrexate Versus Observation in Patients Previously Undiagnosed Peripheral T-cell Lymphoma Who Achieved an Objective Response After Initial Treatment With CHOP-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Peripheral T-cell Lymphoma
Keywords: Lymphoproliferative Disorders
Lymphoma
Non-Hodgkin's Lymphoma
T-cell Lymphoma
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2011-08-22
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From randomization to the date of progression of disease or death due to any cause (up to 76 months)
measure: Overall Survival (OS)
timeFrame: From randomization until death (up to 76 months)
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Up to 2 years
measure: 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
timeFrame: 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)
Other outcomes:
Locations:
city: Novi
country: United States
facility: Detroit Clinical Research Center, PC
state: Michigan
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Center
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy
country: Australia
facility: Saint Vincent's Hospital Melbourne
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Health
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Montreal
country: Canada
facility: Hôpital du Sacré-Coeur de Montréal
state: Quebec
city: Brest
country: France
facility: Hôpital Morvan
city: Pessac
country: France
facility: CHU Haut-Leveque
city: Dublin 8
country: Ireland
facility: St James Hospital
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Ein-Kerem Medical Centre
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
state: Forli
city: Bologna
country: Italy
facility: Az. Ospedaliera Universitaria S. Orsola Malpighi
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
city: Ravenna
country: Italy
facility: Ospedale S. Maria delle Croci
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore
city: Siena
country: Italy
facility: Az. Ospedaliera Università Senese
city: Otahuhu
country: New Zealand
facility: Middlemore Hospital
state: Auckland
city: Auckland
country: New Zealand
facility: Auckland City Hospital / Auckland University
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Milford
country: New Zealand
facility: North Shore Hospital
city: Warszawa
country: Poland
facility: Klinika Nowotworów Ukladu Chlonnego Centrum Onkologii Instytut Marii Sklodowskiej-Curie
state: Mazowieckie
city: Gdansk
country: Poland
facility: Dept of Hematology and Transplantology
city: Kraków
country: Poland
facility: Małopolskie Centrum Medyczne
city: San Juan
country: Puerto Rico
facility: Auxilio Mutuo Cancer Center
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra, Servicio de Hematologia
state: Navarra
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña- Hospital A Coruña
city: Barcelona
country: Spain
facility: Hospital General Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital de Madrid Norte-Sanchinarro
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
state: Cornwall
city: Poole
country: United Kingdom
facility: Poole Hospital NHS Foundation Trust, Poole General Hospital
state: Dorset
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: West Bromwich
country: United Kingdom
facility: Sandwell & West Birmingham Hospitals NHS Trust
state: England
city: Antrim
country: United Kingdom
facility: Antrim Area Hospital
state: Northern Ireland
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde Western Infirmary
state: Scotland
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: Middlesex
country: United Kingdom
facility: Mount Vernon Cancer Centre
city: Warwick
country: United Kingdom
facility: UHCW (University Hospital Coventry and Warwickshire)
Study officials:
References: