Alemtuzumab and CHOP in T-cell Lymphoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Lymphoma, T-Cell, Peripheral

Intervention / Treatment
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* Drug: CHOP14 chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristin, prednison) plus G-CSF, combined with alemtuzumab
* Drug: CHOP14 chemotherapy (see specification under Arm B) plus G-CSF


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br> | Drug: CHOP14 chemotherapy (see specification under Arm B) plus G-CSF<br>* 6 cycles of CHOP every 2 weeks<br>|
| Experimental: Arm B<br> | Drug: CHOP14 chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristin, prednison) plus G-CSF, combined with alemtuzumab<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From the time of randomisation to date of last follow-up or death, up to 96 months | 
| Overall response rate |  | from date of randomization to date of primary response assessment, up to 96 months | 
| Overall response rate related to the CD52 expression |  | From date of randomization to date of primary response assessment, up to 96 months | 
| Tumor control or time-to-progression |  | 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) |  | from randomization to closure of study, up to 96 months | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD52 expression, Lymphoma, T-Cell, Lymphoma, T-Cell, Peripheral, MabCampath, Campath, CHOP-14