Alemtuzumab and CHOP in T-cell Lymphoma

Lymphoma, T-Cell, Peripheral Clinical Trial

— ACT-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00646854
• Other study ID #: 2006-006130-17
• Status: Completed
• Phase: Phase 3
• Start date: June 2008
• Est. completion date: December 31, 2016

Study information

• Verified date: February 2019
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: December 31, 2016
• Est. primary completion date: December 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral

Intervention

Drug:
• CHOP14 chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristin, prednison) plus G-CSF, combined with alemtuzumab
Cyclophosphamide 750 mg/m2 i.v. on day 1 Hydroxydaunorubicin 50 mg/m2 i.v. on day 1 Vincristin 1 mg/m2 i.v. day 1 (max. 2mg) Prednisone 50 mg/m2 p.o. day 1 to 5 Alemtuzumab 30 mg s.c.on day 1 of CHOP-14 cycles 1-4
• CHOP14 chemotherapy (see specification under Arm B) plus G-CSF
6 cycles of CHOP every 2 weeks

Locations

Country	Name	City	State
Austria	AKH Linz	Linz
Austria	Krankenhaus der Elisabethinen	Linz
Austria	Center for Clinical Cancer and Immunology Trials	Salzburg
Austria	Hanusch Krankenhaus	Vienna
Belgium	ZNA Middelheim	Antwerpen
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	AZ St Jan	Brugge
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	UZ VUB	Brussels
Belgium	Grand Hôpital de Charleroi	Charleroi
Belgium	Hôpital de Jolimont	Haine-St-Paul
Belgium	UZ Gasthuisberg	Leuven
Belgium	CHR de la Citadelle	Liége
Belgium	Clinique St Pierre	Ottignies
Belgium	Heilig-Hartziekenhuis	Roeselare
Belgium	Clinique de Mont-Godinne	Yvoir
Czechia	University Hospital Brno	Brno
Czechia	University Hospital Olomouc	Olomouc
Czechia	University Hospital Ostrava	Ostrava
Czechia	University Hospital Kralovske Vinohrady	Prague
Czechia	University Hospital Motol	Prague
Denmark	Aalborg Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense
Denmark	Vejle Hospital	Vejle
Finland	Helsinki University Central Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Oulu University Hospital	Oulu
Finland	Tampere University Hospital	Tampere
Finland	Turku University Central Hospital	Turku
Germany	Charite Universitätsmedizin Berlin	Berlin
Germany	Krankenhaus Nordwest	Frankfurt
Germany	University Hospital Regensburg	Regensburg
Netherlands	Meander Medical Center	Amersfoort
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Vrije University Medical Center	Amsterdam
Netherlands	Haga Ziekenhuis, loc. Leyenburg	Den Haag
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leids University Medical Center	Leiden
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Sint Antonius Ziekenhuis	Nieuwegein
Netherlands	University Medical Center St. Radboud	Nijmegen
Netherlands	Erasmus Medical Center - Centrum	Rotterdam
Netherlands	Erasmus Medical Center Daniel	Rotterdam
Netherlands	Isala Klinieken, Sophia	Zwolle
Norway	Radium Hospital	Oslo
Norway	Stavanger University Hospital	Stavanger
Norway	University Hospital of Nothern Norway	Tromsoe
Norway	St. Olavs Hospital	Trondheim
Poland	Marie Sklodowska-Curie Memorial Institute Cancer Center	Warsaw
Portugal	IPO Lisboa	Lisbon
Portugal	IPO Porto	Porto
Sweden	Sunderby Hospital	Lulea
Sweden	Lund University Hospital	Lund
Sweden	Karolinska University Hospital	Stockholm
Sweden	Norrlands University Hospital	Umea

Sponsors (2)

Lead Sponsor	Collaborator
Aarhus University Hospital	GCP-unit at Aarhus University Hospital, Aarhus, Denmark

Countries where clinical trial is conducted

Austria,  Belgium,  Czechia,  Denmark,  Finland,  Germany,  Netherlands,  Norway,  Poland,  Portugal,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival		The EFS is defined by the time between day of randomization until an event occurs, up to 96 months
Secondary	Overall survival		From the time of randomisation to date of last follow-up or death, up to 96 months
Secondary	Overall response rate		from date of randomization to date of primary response assessment, up to 96 months
Secondary	Overall response rate related to the CD52 expression		From date of randomization to date of primary response assessment, up to 96 months
Secondary	Tumor control or time-to-progression		time of randomization to last follow-up or time of disease progression, up to 96 months
Secondary	Safety measured as number of adverse events (AEs) and serious adverse events (SAEs)		from randomization to closure of study, up to 96 months
Secondary	Feasibility of successful stem cell harvest i.e. >/=2E6 CD34 positive cells		from start of priming regimen to time of assessment of stem cell harvest, up to 96 months