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

Aarhus University Hospital

Status and phase

Completed

Phase 3

Conditions

Lymphoma, T-Cell, Peripheral

Treatments

Drug: CHOP14 chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristin, prednison) plus G-CSF, combined with alemtuzumab

Drug: CHOP14 chemotherapy (see specification under Arm B) plus G-CSF

Study type

Interventional

Funder types

Other

Identifiers

NCT00646854

2006-006130-17

Details and patient eligibility

About

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.

Full 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.

Enrollment

136 patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

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).