Alemtuzumab and CHOP in T-Cell Lymphoma - Full Text View

Sponsors and Collaborators:	Aarhus University Hospital GCP-unit at Aarhus University Hospital, Aarhus, Denmark
Information provided by:	University of Aarhus
ClinicalTrials.gov Identifier:	NCT00646854

Purpose

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	Intervention	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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Cyclophosphamide Campath Granulocyte colony-stimulating factor Alemtuzumab

U.S. FDA Resources

Further study details as provided by University of Aarhus:

Primary Outcome Measures:

Event-free Survival [ Time Frame: The EFS is defined by the time between day of randomization until an event occurs ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Time Frame: From the time of randomisation to date of last follow-up or death ] [ Designated as safety issue: Yes ]
Progression-free survival [ Time Frame: From date of randomization to date of last follow-up or disease progression ] [ Designated as safety issue: No ]
Overall response rate [ Time Frame: from date of randomization to date of primary response assessment ] [ Designated as safety issue: No ]
Overall response rate related to the CD52 expression [ Time Frame: From date of randomization to date of primary response assessment ] [ Designated as safety issue: No ]
Tumor control or time-to-progression [ Time Frame: time of randomization to last follow-up or time of disease progression ] [ Designated as safety issue: No ]
Safety [ Time Frame: from randomization to closure of study ] [ Designated as safety issue: Yes ]
Feasibility of successful stem cell harvest. [ Time Frame: from start of priming regimen to time of assessment of stem cell harvest ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	308
Study Start Date:	November 2007
Estimated Study Completion Date:	February 2014
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm A: Active Comparator	Drug: CHOP14 chemotherapy (see specification under Arm B) plus G-CSF 6 cycles of CHOP every 2 weeks
Arm B: Experimental	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 and 2 of each CHOP-14 cycle

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 and day 2 in combination with each chemotherapy cycle. 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 anaplastic large cell lymphoma Planned Sample Size: 308 young patients (18-65 yrs) registered and randomized Total Number of Centers: This study will be proposed to main European and Australian Study Groups.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
Primary systemic, alk-negative anaplastic large cell lymphoma (T- or null phenotype)
Subcutaneous panniculitis-like T-NHL
Hepatosplenic T-cell lymphoma
Extranodal NK/T cell lymphoma, nasal type
Age 18-65 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 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
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00646854

Contacts

Contact: Francesco d'Amore, Associate Professor, Dr.med

+ 45 8949 7567

OVL05FD@as.aaa.dk

Locations

Denmark
Aarhus University Hospital	Recruiting
Aarhus, Denmark, 8000
Contact: Francesco d'Amore, M.D. + 45 8949 7567 OVL05FD@as.aaa.dk
Principal Investigator: Francesco d'Amore, M.D.
Vejle Hospital	Recruiting
Vejle, Denmark, DK-7100
Contact: Ole Gadeberg +45 7940 6310 ole.vestergaard.gadeberg@vgs.regionsyddanmark.dk
Principal Investigator: Ole Gadeberg, MD
Rigshospitalet	Recruiting
Copenhagen, Denmark, DK-2100
Contact: Peter Brown, MD peter.brown@rh.regionh.dk
Principal Investigator: Peter Brown, MD
Herlev Hospital	Recruiting
Herlev, Denmark, DK-2730
Contact: Per Hansen, MD peboha01@heh.regionh.dk
Principal Investigator: Per Hansen, MD
Portugal
IPO Lisboa	Recruiting
Lisbon, Portugal, 1099-023
Contact: Maria Gomes da Silva, MD mgsilva@ipolisboa.minsaude.pt
Principal Investigator: Maria Gomes da Silva, MD
Hospital de Santa Maria	Not yet recruiting
Lisbon, Portugal, 1649-035
Contact: Joao Raposo, MD joao.raposo@hsm.minsaude.pt
Principal Investigator: Joao Raposo, MD
IPO Porto	Not yet recruiting
Porto, Portugal, 4200-072
Contact: Jose Mariz, MD mariz@ipoporto.minsaude.pt
Principal Investigator: Jose Mariz, MD
Sweden
Lund University Hospital	Recruiting
Lund, Sweden, S-221 85
Contact: Thomas Relander, MD thomas.relander@med.lu.se
Principal Investigator: Thomas Relander, MD
Malmo University Hospital	Recruiting
Malmo, Sweden, S-205 02
Contact: Anders Radlund, MD anders.radlund@skane.se
Principal Investigator: Anders Radlund, MD
Norrlands University Hospital	Recruiting
Umea, Sweden, S-901 85
Contact: Martin Erlanson, MD martin.erlanson@vll.se
Principal Investigator: Martin Erlanson, MD
Karolinska University Hospital	Recruiting
Stockholm, Sweden, S-141 86
Contact: Mats Merup, MD mats.merup@ki.se
Principal Investigator: Mats Merup, MD
Sunderby Hospital	Recruiting
Lulea, Sweden, S-971 80
Contact: Lena Brandefors, MD lena.brandefors@nll.se
Principal Investigator: Lena Brandefors, MD

Sponsors and Collaborators

Aarhus University Hospital

GCP-unit at Aarhus University Hospital, Aarhus, Denmark

Investigators

Principal Investigator:

Francesco d'Amore, Associate Professor, Dr.med

Dept. of Hematology, Århus University Hospital, Denmark

More Information

No publications provided

Responsible Party:	Aarhus University Hospital ( Associate professor Francesco d'Amore )
Study ID Numbers:	2006-006130-17
Study First Received:	February 14, 2008
Last Updated:	November 10, 2008
ClinicalTrials.gov Identifier:	NCT00646854 History of Changes
Health Authority:	Denmark: Danish Medicines Agency; Denmark: Ethics Committee; Denmark: Danish Dataprotection Agency

Keywords provided by University of Aarhus:

Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
MabCampath

Campath
CHOP-14
CD52 expression

Study placed in the following topic categories:

Prednisone
Peripheral T-cell Lymphoma
Immunoproliferative Disorders
Immunologic Factors
Cyclophosphamide
Immunosuppressive Agents
Lymphoma, T-Cell, Peripheral
Antibodies, Monoclonal
Lymphatic Diseases
Antibodies

Lymphoma, T-Cell
Alemtuzumab
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Alkylating Agents
Lymphoma
Immunoglobulins

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Lymphoma, T-Cell, Peripheral
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases

Neoplasms
Therapeutic Uses
Lymphoma, T-Cell
Alemtuzumab
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Alkylating Agents
Lymphoma

ClinicalTrials.gov processed this record on July 06, 2009