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

Sponsor:	Aarhus University Hospital
Collaborator:	GCP-unit at Aarhus University Hospital, Aarhus, Denmark
Information provided by (Responsible Party):	University of Aarhus ( Aarhus University Hospital )
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 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride 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, up to 96 months ] [ 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, up to 96 months ] [ Designated as safety issue: Yes ]
Overall response rate [ Time Frame: from date of randomization to date of primary response assessment, up to 96 months ] [ 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, up to 96 months ] [ 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, up to 96 months ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	308
Study Start Date:	June 2008
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	18 Years to 60 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
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

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

Contacts

Contact: Francesco d'Amore, Prof

+ 45 8949 7567

frandamo@rm.dk

Show 61 Study Locations

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

More Information

No publications provided

Responsible Party:	University of Aarhus ( Aarhus University Hospital )
ClinicalTrials.gov Identifier:	NCT00646854 History of Changes
Other Study ID Numbers:	2006-006130-17
Study First Received:	February 14, 2008
Last Updated:	March 20, 2012
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

Additional relevant MeSH terms:

Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Campath 1G
Alemtuzumab

Doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on May 22, 2012