Clinical trial NCT00646854: Alemtuzumab and CHOP in T-cell Lymphoma
Official title: A Randomized Phase III Study to Evaluate the Efficacy of Chemoimmunotherapy With the Monoclonal Antibody Campath-1H (Alemtuzumab) Given in Combination With 2-weekly CHOP Versus 2-weekly CHOP Alone and Consolidated by Autologous Stem Cell Transplant, in Young Patients With Previously Untreated Systemic Peripheral T-cell Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma, T-Cell, Peripheral
Keywords: Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
MabCampath
Campath
CHOP-14
CD52 expression
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: GCP-unit at Aarhus University Hospital, Aarhus, Denmark
First posted: 2008-03-31
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine efficacy and safety of the monoclonal antibody MabCampath® (alemtuzumab) combined with chemotherapy in the treatment of T-cell lymphoma.

Detailed description: First International phase III T-cell lymphoma study Indication:Newly diagnosed non-cutaneous peripheral T-cell lymphoma Study objectives:Determination of the efficacy and safety of the monoclonal antibody MabCampath® (alemtuzumab) combined with two-weekly CHOP supported by G-CSF Primary Endpoint: Event-Free-Survival (EFS) Study Design: International open-label, multicentre, randomized Phase III Study

Study Medication: Patients are randomized to six cycles of two-weekly CHOP plus G-CSF with or without alemtuzumab given subcutaneously 30 mg day 1 in combination with chemotherapy cycles 1-4. Patients in CR, CRu and PR after the 6 cycles of CHOP14 combined or not with alemtuzumab will receive a consolidation with high-dose chemotherapy followed by autologous stem cell transplantation.

Patient Population: Patients \> 18 yrs with newly diagnosed non-cutaneous, non-leukemic PTCL, except alk-protein positive and negative anaplastic large cell lymphoma Planned Sample Size: 308 young patients (18-60 yrs) registered and randomized Total Number of Centers: This study will be proposed to main European and Australian Study Groups.

Eligibility criteria: Inclusion criteria:

* Previously untreated patients with newly diagnosed peripheral T-cell lymphoma of stage I bulk (≥ 7.5 cm) and stages II to IV.
* Patients with a confirmed histologic diagnosis of peripheral T-cell NHL according to the WHO classification:
* Peripheral T-cell lymphoma, unspecified (PTCL NOS)
* Angioimmunoblastic T-cell lymphoma
* Enteropathy-type T cell lymphoma
* Subcutaneous panniculitis-like T-NHL (gamma-delta T-cell lymphoma)
* Hepatosplenic T-cell lymphoma
* Extranodal NK/T cell lymphoma, nasal type
* Age 18-60 years at time of randomization
* Life expectancy of 3 months or longer
* ECOG performance status (PS) 0, 1 or 2 at the time of randomization. However, PS 3 will be acceptable if lymphoma-related.
* Measurable disease (defined as at least one lesion with two measurable perpendicular diameters of which at least one should be \>= 15 mm).
* Written informed consent

Exclusion Criteria:

* Patients with NK/T-NHL of the following type:
* Precursor T cell lymphoblastic lymphoma/leukemia
* All mature T cell leukemias (T-PLL, ATLL, NK cell leukemia, T-LGL, HTLV1-pos ATL)
* Alk-positive and negative anaplastic large cell lymphoma
* Blastic NK cell lymphoma
* Cutaneous T-cell lymphoma, transformed or not
* Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection), which could compromise participation in the study.
* Known hypersensitivity to murine or chimeric antibodies or proteins
* Severe cardiac dysfunction (NYHA classification II-IV, Appendix H) or LVEF \< 45 %
* Significant renal dysfunction, i.e. serum creatinin \>2 times upper normal level (UNL), unless related to NHL
* Significant hepatic dysfunction (total bilirubin \>2 times UNL or transaminases \>= 2.5 times UNL), unless related to NHL
* Impaired pulmonary functions; in this case, the patient is to be excluded if the resultant pulmonary function test shows FEV1\<50% or a diffusion capacity \<50% of the reference values
* Suspected or documented Central Nervous System involvement by NHL
* Patients known to be HIV-positive
* Patients with active, uncontrolled infections, especially known seropositivity for HCV or HbsAg
* Patients with uncontrolled asthma or allergy, requiring systemic steroid treatment
* Prior treatment with chemotherapy, radiotherapy or immunotherapy for this lymphoma, except local radiotherapy in case of extranodal NK/T cell lymphoma, nasal or nasal type
* History of active cancer during the past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma
* Unwillingness or inability to comply with the protocol
* Simultaneous participation in any other study protocol
* Pregnant and nursing women (Women of childbearing potential should use safe anticonceptives) Contraceptive pills, intrauterine devices, injection of prolonged gestagen, subdermal implantation, hormonal vaginal devices and transdermal patches are considered as safe contraceptive methods).

Primary outcomes:
measure: Event-free Survival
timeFrame: The EFS is defined by the time between day of randomization until an event occurs, up to 96 months
Secondary outcomes:
measure: Overall survival
timeFrame: From the time of randomisation to date of last follow-up or death, up to 96 months
measure: Overall response rate
timeFrame: from date of randomization to date of primary response assessment, up to 96 months
measure: Overall response rate related to the CD52 expression
timeFrame: From date of randomization to date of primary response assessment, up to 96 months
measure: Tumor control or time-to-progression
timeFrame: time of randomization to last follow-up or time of disease progression, up to 96 months
measure: Safety measured as number of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: from randomization to closure of study, up to 96 months
measure: Feasibility of successful stem cell harvest i.e. >/=2E6 CD34 positive cells
timeFrame: from start of priming regimen to time of assessment of stem cell harvest, up to 96 months
Other outcomes:
Locations:
city: Linz
country: Austria
facility: AKH Linz
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen
city: Salzburg
country: Austria
facility: Center for Clinical Cancer and Immunology Trials
city: Vienna
country: Austria
facility: Hanusch Krankenhaus
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Brugge
country: Belgium
facility: AZ St Jan
city: Brussels
country: Belgium
facility: UZ VUB
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Haine-St-Paul
country: Belgium
facility: Hôpital de Jolimont
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Liége
country: Belgium
facility: CHR de la Citadelle
city: Ottignies
country: Belgium
facility: Clinique St Pierre
city: Roeselare
country: Belgium
facility: Heilig-Hartziekenhuis
city: Yvoir
country: Belgium
facility: Clinique de Mont-Godinne
city: Brno
country: Czechia
facility: University Hospital Brno
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Prague
country: Czechia
facility: University Hospital Kralovske Vinohrady
city: Prague
country: Czechia
facility: University Hospital Motol
city: Aalborg
country: Denmark
facility: Aalborg Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Central Hospital
city: Berlin
country: Germany
facility: Charite Universitätsmedizin Berlin
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest
city: Regensburg
country: Germany
facility: University Hospital Regensburg
city: Amersfoort
country: Netherlands
facility: Meander Medical Center
city: Amsterdam
country: Netherlands
facility: Vrije University Medical Center
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Den Haag
country: Netherlands
facility: Haga Ziekenhuis, loc. Leyenburg
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leids University Medical Center
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
city: Nijmegen
country: Netherlands
facility: University Medical Center St. Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center - Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center Daniel
city: Zwolle
country: Netherlands
facility: Isala Klinieken, Sophia
city: Oslo
country: Norway
facility: Radium Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsoe
country: Norway
facility: University Hospital of Nothern Norway
city: Trondheim
country: Norway
facility: St. Olavs Hospital
city: Warsaw
country: Poland
facility: Marie Sklodowska-Curie Memorial Institute Cancer Center
city: Lisbon
country: Portugal
facility: IPO Lisboa
city: Porto
country: Portugal
facility: IPO Porto
city: Lulea
country: Sweden
facility: Sunderby Hospital
city: Lund
country: Sweden
facility: Lund University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umea
country: Sweden
facility: Norrlands University Hospital
Study officials:
affiliation: Dept. of Hematology, Århus University Hospital, Denmark
name: Francesco d'Amore, Prof
role: PRINCIPAL_INVESTIGATOR
References: