ACT-1: Alemtuzumab and CHOP in T-cell Lymphoma

• Sponsor: Aarhus University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00646854
• Collaborator: GCP-unit at Aarhus University Hospital, Aarhus, Denmark (Other)
• Enrollment: 136
• Locations: 59
• Arms: 2
• Actual Duration (Months): 103
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, T-Cell, Peripheral	Drug: CHOP14 chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristin, prednison) plus G-CSF, combined with alemtuzumab; Drug: CHOP14 chemotherapy (see specification under Arm B) plus G-CSF	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 136 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Dec 31, 2016
• Actual Study Completion Date: Dec 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A	Drug: CHOP14 chemotherapy (see specification under Arm B) plus G-CSF; 6 cycles of CHOP every 2 weeks
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

Outcome Measures

Primary Outcome Measures

1. Event-free Survival [The EFS is defined by the time between day of randomization until an event occurs, up to 96 months]

Secondary Outcome Measures

1. Overall survival [From the time of randomisation to date of last follow-up or death, up to 96 months]

2. Overall response rate [from date of randomization to date of primary response assessment, up to 96 months]

3. Overall response rate related to the CD52 expression [From date of randomization to date of primary response assessment, up to 96 months]

4. Tumor control or time-to-progression [time of randomization to last follow-up or time of disease progression, up to 96 months]

5. Safety measured as number of adverse events (AEs) and serious adverse events (SAEs) [from randomization to closure of study, up to 96 months]

6. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AKH Linz	Linz		Austria	4020
2	Krankenhaus der Elisabethinen	Linz		Austria	4020
3	Center for Clinical Cancer and Immunology Trials	Salzburg		Austria	5020
4	Hanusch Krankenhaus	Vienna		Austria	1140
5	ZNA Middelheim	Antwerpen		Belgium	2020
6	ZNA Stuivenberg	Antwerpen		Belgium	2020
7	AZ St Jan	Brugge		Belgium	8000
8	UZ VUB	Brussels		Belgium	1090
9	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
10	Grand Hôpital de Charleroi	Charleroi		Belgium	6000
11	Hôpital de Jolimont	Haine-St-Paul		Belgium	7100
12	UZ Gasthuisberg	Leuven		Belgium	3000
13	CHR de la Citadelle	Liége		Belgium	4000
14	Clinique St Pierre	Ottignies		Belgium	1340
15	Heilig-Hartziekenhuis	Roeselare		Belgium	8800
16	Clinique de Mont-Godinne	Yvoir		Belgium	5530
17	University Hospital Brno	Brno		Czechia	625 00
18	University Hospital Olomouc	Olomouc		Czechia	775 20
19	University Hospital Ostrava	Ostrava		Czechia	70852
20	University Hospital Kralovske Vinohrady	Prague		Czechia	100 34
21	University Hospital Motol	Prague		Czechia	150 00
22	Aalborg Hospital	Aalborg		Denmark	9000
23	Aarhus University Hospital	Aarhus		Denmark	8000
24	Rigshospitalet	Copenhagen		Denmark	DK-2100
25	Herlev Hospital	Herlev		Denmark	DK-2730
26	Odense University Hospital	Odense		Denmark	DK-5000
27	Vejle Hospital	Vejle		Denmark	DK-7100
28	Helsinki University Central Hospital	Helsinki		Finland	00029
29	Kuopio University Hospital	Kuopio		Finland	70211
30	Oulu University Hospital	Oulu		Finland	90029
31	Tampere University Hospital	Tampere		Finland	33521
32	Turku University Central Hospital	Turku		Finland	20521
33	Charite Universitätsmedizin Berlin	Berlin		Germany	D-13353
34	Krankenhaus Nordwest	Frankfurt		Germany	D-60488
35	University Hospital Regensburg	Regensburg		Germany	D-93042
36	Meander Medical Center	Amersfoort		Netherlands	NL-3800 BM
37	Vrije University Medical Center	Amsterdam		Netherlands	NL-1007 MB
38	Academisch Medisch Centrum	Amsterdam		Netherlands	NL-1100 DD
39	Haga Ziekenhuis, loc. Leyenburg	Den Haag		Netherlands	NL-2504 LN
40	Medisch Spectrum Twente	Enschede		Netherlands	NL-7500 KA
41	University Medical Center Groningen	Groningen		Netherlands	NL-9700 RB
42	Leids University Medical Center	Leiden		Netherlands	NL-2300 RC
43	Academisch Ziekenhuis Maastricht	Maastricht		Netherlands	NL-6202 AZ
44	Sint Antonius Ziekenhuis	Nieuwegein		Netherlands	NL-3430 EM
45	University Medical Center St. Radboud	Nijmegen		Netherlands	NL-6500 HB
46	Erasmus Medical Center - Centrum	Rotterdam		Netherlands	NL-3075 EA
47	Erasmus Medical Center Daniel	Rotterdam		Netherlands	NL-3075 EA
48	Isala Klinieken, Sophia	Zwolle		Netherlands	NL-8000 GK
49	Radium Hospital	Oslo		Norway	N-0310
50	Stavanger University Hospital	Stavanger		Norway	N-4068
51	University Hospital of Nothern Norway	Tromsoe		Norway	N-9038
52	St. Olavs Hospital	Trondheim		Norway	N-7030
53	Marie Sklodowska-Curie Memorial Institute Cancer Center	Warsaw		Poland	02-781
54	IPO Lisboa	Lisbon		Portugal	1099-023
55	IPO Porto	Porto		Portugal	4200-072
56	Sunderby Hospital	Lulea		Sweden	S-971 80
57	Lund University Hospital	Lund		Sweden	S-221 85
58	Karolinska University Hospital	Stockholm		Sweden	S-141 86
59	Norrlands University Hospital	Umea		Sweden	S-901 85

Sponsors and Collaborators

• Aarhus University Hospital
• GCP-unit at Aarhus University Hospital, Aarhus, Denmark

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Aarhus University Hospital
• ClinicalTrials.gov Identifier: NCT00646854
• Other Study ID Numbers: 2006-006130-17
• First Posted: Mar 31, 2008
• Last Update Posted: Mar 1, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Aarhus University Hospital: Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; MabCampath; Campath; CHOP-14; CD52 expression
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Cyclophosphamide; Alemtuzumab; Doxorubicin; Liposomal doxorubicin; Vincristine; Lenograstim

Study Results

No Results Posted as of Mar 1, 2019