Alemtuzumab and CHOP in T-cell Lymphoma (ACT-1)
Primary Purpose
Lymphoma, T-Cell, Peripheral
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
CHOP14 chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristin, prednison) plus G-CSF, combined with alemtuzumab
CHOP14 chemotherapy (see specification under Arm B) plus G-CSF
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, T-Cell, Peripheral focused on measuring Lymphoma, T-Cell, Lymphoma, T-Cell, Peripheral, MabCampath, Campath, CHOP-14, CD52 expression
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).
Sites / Locations
- AKH Linz
- Krankenhaus der Elisabethinen
- Center for Clinical Cancer and Immunology Trials
- Hanusch Krankenhaus
- ZNA Middelheim
- ZNA Stuivenberg
- AZ St Jan
- UZ VUB
- Cliniques Universitaires Saint-Luc
- Grand Hôpital de Charleroi
- Hôpital de Jolimont
- UZ Gasthuisberg
- CHR de la Citadelle
- Clinique St Pierre
- Heilig-Hartziekenhuis
- Clinique de Mont-Godinne
- University Hospital Brno
- University Hospital Olomouc
- University Hospital Ostrava
- University Hospital Kralovske Vinohrady
- University Hospital Motol
- Aalborg Hospital
- Aarhus University Hospital
- Rigshospitalet
- Herlev Hospital
- Odense University Hospital
- Vejle Hospital
- Helsinki University Central Hospital
- Kuopio University Hospital
- Oulu University Hospital
- Tampere University Hospital
- Turku University Central Hospital
- Charite Universitätsmedizin Berlin
- Krankenhaus Nordwest
- University Hospital Regensburg
- Meander Medical Center
- Vrije University Medical Center
- Academisch Medisch Centrum
- Haga Ziekenhuis, loc. Leyenburg
- Medisch Spectrum Twente
- University Medical Center Groningen
- Leids University Medical Center
- Academisch Ziekenhuis Maastricht
- Sint Antonius Ziekenhuis
- University Medical Center St. Radboud
- Erasmus Medical Center - Centrum
- Erasmus Medical Center Daniel
- Isala Klinieken, Sophia
- Radium Hospital
- Stavanger University Hospital
- University Hospital of Nothern Norway
- St. Olavs Hospital
- Marie Sklodowska-Curie Memorial Institute Cancer Center
- IPO Lisboa
- IPO Porto
- Sunderby Hospital
- Lund University Hospital
- Karolinska University Hospital
- Norrlands University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Arm A
Arm B
Arm Description
Outcomes
Primary Outcome Measures
Event-free Survival
Secondary Outcome Measures
Overall survival
Overall response rate
Overall response rate related to the CD52 expression
Tumor control or time-to-progression
Safety measured as number of adverse events (AEs) and serious adverse events (SAEs)
Feasibility of successful stem cell harvest i.e. >/=2E6 CD34 positive cells
Full Information
NCT ID
NCT00646854
First Posted
February 14, 2008
Last Updated
February 27, 2019
Sponsor
Aarhus University Hospital
Collaborators
GCP-unit at Aarhus University Hospital, Aarhus, Denmark
1. Study Identification
Unique Protocol Identification Number
NCT00646854
Brief Title
Alemtuzumab and CHOP in T-cell Lymphoma
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
June 2008 (Actual)
Primary Completion Date
December 31, 2016 (Actual)
Study Completion Date
December 31, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aarhus University Hospital
Collaborators
GCP-unit at Aarhus University Hospital, Aarhus, Denmark
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, T-Cell, Peripheral
Keywords
Lymphoma, T-Cell, Lymphoma, T-Cell, Peripheral, MabCampath, Campath, CHOP-14, CD52 expression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
136 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Active Comparator
Arm Title
Arm B
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
CHOP14 chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristin, prednison) plus G-CSF, combined with alemtuzumab
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
CHOP14 chemotherapy (see specification under Arm B) plus G-CSF
Intervention Description
6 cycles of CHOP every 2 weeks
Primary Outcome Measure Information:
Title
Event-free Survival
Time Frame
The EFS is defined by the time between day of randomization until an event occurs, up to 96 months
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
From the time of randomisation to date of last follow-up or death, up to 96 months
Title
Overall response rate
Time Frame
from date of randomization to date of primary response assessment, up to 96 months
Title
Overall response rate related to the CD52 expression
Time Frame
From date of randomization to date of primary response assessment, up to 96 months
Title
Tumor control or time-to-progression
Time Frame
time of randomization to last follow-up or time of disease progression, up to 96 months
Title
Safety measured as number of adverse events (AEs) and serious adverse events (SAEs)
Time Frame
from randomization to closure of study, up to 96 months
Title
Feasibility of successful stem cell harvest i.e. >/=2E6 CD34 positive cells
Time Frame
from start of priming regimen to time of assessment of stem cell harvest, up to 96 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco d'Amore, Prof
Organizational Affiliation
Dept. of Hematology, Århus University Hospital, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
AKH Linz
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
Krankenhaus der Elisabethinen
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
Center for Clinical Cancer and Immunology Trials
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Hanusch Krankenhaus
City
Vienna
ZIP/Postal Code
1140
Country
Austria
Facility Name
ZNA Middelheim
City
Antwerpen
ZIP/Postal Code
2020
Country
Belgium
Facility Name
ZNA Stuivenberg
City
Antwerpen
ZIP/Postal Code
2020
Country
Belgium
Facility Name
AZ St Jan
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
UZ VUB
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Grand Hôpital de Charleroi
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
Hôpital de Jolimont
City
Haine-St-Paul
ZIP/Postal Code
7100
Country
Belgium
Facility Name
UZ Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHR de la Citadelle
City
Liége
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Clinique St Pierre
City
Ottignies
ZIP/Postal Code
1340
Country
Belgium
Facility Name
Heilig-Hartziekenhuis
City
Roeselare
ZIP/Postal Code
8800
Country
Belgium
Facility Name
Clinique de Mont-Godinne
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
University Hospital Brno
City
Brno
ZIP/Postal Code
625 00
Country
Czechia
Facility Name
University Hospital Olomouc
City
Olomouc
ZIP/Postal Code
775 20
Country
Czechia
Facility Name
University Hospital Ostrava
City
Ostrava
ZIP/Postal Code
70852
Country
Czechia
Facility Name
University Hospital Kralovske Vinohrady
City
Prague
ZIP/Postal Code
100 34
Country
Czechia
Facility Name
University Hospital Motol
City
Prague
ZIP/Postal Code
150 00
Country
Czechia
Facility Name
Aalborg Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
DK-2100
Country
Denmark
Facility Name
Herlev Hospital
City
Herlev
ZIP/Postal Code
DK-2730
Country
Denmark
Facility Name
Odense University Hospital
City
Odense
ZIP/Postal Code
DK-5000
Country
Denmark
Facility Name
Vejle Hospital
City
Vejle
ZIP/Postal Code
DK-7100
Country
Denmark
Facility Name
Helsinki University Central Hospital
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Facility Name
Kuopio University Hospital
City
Kuopio
ZIP/Postal Code
70211
Country
Finland
Facility Name
Oulu University Hospital
City
Oulu
ZIP/Postal Code
90029
Country
Finland
Facility Name
Tampere University Hospital
City
Tampere
ZIP/Postal Code
33521
Country
Finland
Facility Name
Turku University Central Hospital
City
Turku
ZIP/Postal Code
20521
Country
Finland
Facility Name
Charite Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
D-13353
Country
Germany
Facility Name
Krankenhaus Nordwest
City
Frankfurt
ZIP/Postal Code
D-60488
Country
Germany
Facility Name
University Hospital Regensburg
City
Regensburg
ZIP/Postal Code
D-93042
Country
Germany
Facility Name
Meander Medical Center
City
Amersfoort
ZIP/Postal Code
NL-3800 BM
Country
Netherlands
Facility Name
Vrije University Medical Center
City
Amsterdam
ZIP/Postal Code
NL-1007 MB
Country
Netherlands
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
NL-1100 DD
Country
Netherlands
Facility Name
Haga Ziekenhuis, loc. Leyenburg
City
Den Haag
ZIP/Postal Code
NL-2504 LN
Country
Netherlands
Facility Name
Medisch Spectrum Twente
City
Enschede
ZIP/Postal Code
NL-7500 KA
Country
Netherlands
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
NL-9700 RB
Country
Netherlands
Facility Name
Leids University Medical Center
City
Leiden
ZIP/Postal Code
NL-2300 RC
Country
Netherlands
Facility Name
Academisch Ziekenhuis Maastricht
City
Maastricht
ZIP/Postal Code
NL-6202 AZ
Country
Netherlands
Facility Name
Sint Antonius Ziekenhuis
City
Nieuwegein
ZIP/Postal Code
NL-3430 EM
Country
Netherlands
Facility Name
University Medical Center St. Radboud
City
Nijmegen
ZIP/Postal Code
NL-6500 HB
Country
Netherlands
Facility Name
Erasmus Medical Center - Centrum
City
Rotterdam
ZIP/Postal Code
NL-3075 EA
Country
Netherlands
Facility Name
Erasmus Medical Center Daniel
City
Rotterdam
ZIP/Postal Code
NL-3075 EA
Country
Netherlands
Facility Name
Isala Klinieken, Sophia
City
Zwolle
ZIP/Postal Code
NL-8000 GK
Country
Netherlands
Facility Name
Radium Hospital
City
Oslo
ZIP/Postal Code
N-0310
Country
Norway
Facility Name
Stavanger University Hospital
City
Stavanger
ZIP/Postal Code
N-4068
Country
Norway
Facility Name
University Hospital of Nothern Norway
City
Tromsoe
ZIP/Postal Code
N-9038
Country
Norway
Facility Name
St. Olavs Hospital
City
Trondheim
ZIP/Postal Code
N-7030
Country
Norway
Facility Name
Marie Sklodowska-Curie Memorial Institute Cancer Center
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Facility Name
IPO Lisboa
City
Lisbon
ZIP/Postal Code
1099-023
Country
Portugal
Facility Name
IPO Porto
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
Sunderby Hospital
City
Lulea
ZIP/Postal Code
S-971 80
Country
Sweden
Facility Name
Lund University Hospital
City
Lund
ZIP/Postal Code
S-221 85
Country
Sweden
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
S-141 86
Country
Sweden
Facility Name
Norrlands University Hospital
City
Umea
ZIP/Postal Code
S-901 85
Country
Sweden
12. IPD Sharing Statement
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Alemtuzumab and CHOP in T-cell Lymphoma
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