Alemtuzumab and CHOP in T-cell Lymphoma (ACT-1)

February 27, 2019 updated by: Aarhus University Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

136

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Linz, Austria, 4020
        • Krankenhaus der Elisabethinen
      • Linz, Austria, 4020
        • AKH Linz
      • Salzburg, Austria, 5020
        • Center for Clinical Cancer and Immunology Trials
      • Vienna, Austria, 1140
        • Hanusch Krankenhaus
  • Belgium
      • Antwerpen, Belgium, 2020
        • ZNA Middelheim
      • Antwerpen, Belgium, 2020
        • ZNA Stuivenberg
      • Brugge, Belgium, 8000
        • AZ St Jan
      • Brussels, Belgium, 1200
        • Cliniques universitaires Saint-Luc
      • Brussels, Belgium, 1090
        • UZ VUB
      • Charleroi, Belgium, 6000
        • Grand Hôpital de Charleroi
      • Haine-St-Paul, Belgium, 7100
        • Hopital De Jolimont
      • Leuven, Belgium, 3000
        • UZ Gasthuisberg
      • Liége, Belgium, 4000
        • CHR de la Citadelle
      • Ottignies, Belgium, 1340
        • Clinique St Pierre
      • Roeselare, Belgium, 8800
        • Heilig-Hartziekenhuis
      • Yvoir, Belgium, 5530
        • Clinique de Mont-Godinne
  • Czechia
      • Brno, Czechia, 625 00
        • University Hospital Brno
      • Olomouc, Czechia, 775 20
        • University hospital Olomouc
      • Ostrava, Czechia, 70852
        • University Hospital Ostrava
      • Prague, Czechia, 100 34
        • University Hospital Kralovske Vinohrady
      • Prague, Czechia, 150 00
        • University Hospital Motol
  • Denmark
      • Aalborg, Denmark, 9000
        • Aalborg Hospital
      • Aarhus, Denmark, 8000
        • Aarhus University Hospital
      • Copenhagen, Denmark, DK-2100
        • Rigshospitalet
      • Herlev, Denmark, DK-2730
        • Herlev Hospital
      • Odense, Denmark, DK-5000
        • Odense University Hospital
      • Vejle, Denmark, DK-7100
        • Vejle Hospital
  • Finland
      • Helsinki, Finland, 00029
        • Helsinki University Central Hospital
      • Kuopio, Finland, 70211
        • Kuopio University Hospital
      • Oulu, Finland, 90029
        • Oulu University Hospital
      • Tampere, Finland, 33521
        • Tampere University Hospital
      • Turku, Finland, 20521
        • Turku University Central Hospital
  • Germany
      • Berlin, Germany, D-13353
        • Charité Universitätsmedizin Berlin
      • Frankfurt, Germany, D-60488
        • Krankenhaus Nordwest
      • Regensburg, Germany, D-93042
        • University Hospital Regensburg
  • Netherlands
      • Amersfoort, Netherlands, NL-3800 BM
        • Meander Medical Center
      • Amsterdam, Netherlands, NL-1007 MB
        • Vrije University Medical Center
      • Amsterdam, Netherlands, NL-1100 DD
        • Academisch Medisch Centrum
      • Den Haag, Netherlands, NL-2504 LN
        • Haga Ziekenhuis, loc. Leyenburg
      • Enschede, Netherlands, NL-7500 KA
        • Medisch Spectrum Twente
      • Groningen, Netherlands, NL-9700 RB
        • University Medical Center Groningen
      • Leiden, Netherlands, NL-2300 RC
        • Leids University Medical Center
      • Maastricht, Netherlands, NL-6202 AZ
        • Academisch Ziekenhuis Maastricht
      • Nieuwegein, Netherlands, NL-3430 EM
        • Sint Antonius Ziekenhuis
      • Nijmegen, Netherlands, NL-6500 HB
        • University Medical Center St. Radboud
      • Rotterdam, Netherlands, NL-3075 EA
        • Erasmus Medical Center - Centrum
      • Rotterdam, Netherlands, NL-3075 EA
        • Erasmus Medical Center Daniel
      • Zwolle, Netherlands, NL-8000 GK
        • Isala Klinieken, Sophia
  • Norway
      • Oslo, Norway, N-0310
        • Radium Hospital
      • Stavanger, Norway, N-4068
        • Stavanger University Hospital
      • Tromsoe, Norway, N-9038
        • University Hospital of Nothern Norway
      • Trondheim, Norway, N-7030
        • St. Olavs Hospital
  • Poland
      • Warsaw, Poland, 02-781
        • Marie Sklodowska-Curie Memorial Institute Cancer Center
  • Portugal
      • Lisbon, Portugal, 1099-023
        • Ipo Lisboa
      • Porto, Portugal, 4200-072
        • IPO Porto
  • Sweden
      • Lulea, Sweden, S-971 80
        • Sunderby Hospital
      • Lund, Sweden, S-221 85
        • Lund University Hospital
      • Stockholm, Sweden, S-141 86
        • Karolinska University Hospital
      • Umea, Sweden, S-901 85
        • Norrlands University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm B
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
ACTIVE_COMPARATOR: Arm A
Drug: CHOP14 chemotherapy (see specification under Arm B) plus G-CSF
6 cycles of CHOP every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Event-free Survival
Time Frame: The EFS is defined by the time between day of randomization until an event occurs, up to 96 months
The EFS is defined by the time between day of randomization until an event occurs, up to 96 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: From the time of randomisation to date of last follow-up or death, up to 96 months
From the time of randomisation to date of last follow-up or death, up to 96 months
Overall response rate
Time Frame: from date of randomization to date of primary response assessment, up to 96 months
from date of randomization to date of primary response assessment, up to 96 months
Overall response rate related to the CD52 expression
Time Frame: From date of randomization to date of primary response assessment, up to 96 months
From date of randomization to date of primary response assessment, up to 96 months
Tumor control or time-to-progression
Time Frame: time of randomization to last follow-up or time of disease progression, up to 96 months
time of randomization to last follow-up or time of disease progression, up to 96 months
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
from randomization to closure of study, up to 96 months
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
from start of priming regimen to time of assessment of stem cell harvest, up to 96 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aarhus University Hospital

Collaborators

GCP-unit at Aarhus University Hospital, Aarhus, Denmark

Investigators

  • Principal Investigator: Francesco d'Amore, Prof, Dept. of Hematology, Århus University Hospital, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 1, 2008

Primary Completion (ACTUAL)

December 31, 2016

Study Completion (ACTUAL)

December 31, 2016

Study Registration Dates

First Submitted

February 14, 2008

First Submitted That Met QC Criteria

March 26, 2008

First Posted (ESTIMATE)

March 31, 2008

Study Record Updates

Last Update Posted (ACTUAL)

March 1, 2019

Last Update Submitted That Met QC Criteria

February 27, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006-006130-17

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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