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
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Aarhus University Hospital
- Enrollment
- 136
- Locations
- 59
- Primary Endpoint
- Event-free Survival
Overview
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.
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
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
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
Arms & Interventions
Arm A
Intervention: CHOP14 chemotherapy (see specification under Arm B) plus G-CSF (Drug)
Arm B
Intervention: CHOP14 chemotherapy (cyclophosphamide, hydroxydaunorubicin, vincristin, prednison) plus G-CSF, combined with alemtuzumab (Drug)
Outcomes
Primary Outcomes
Event-free Survival
Time Frame: The EFS is defined by the time between day of randomization until an event occurs, up to 96 months
Secondary Outcomes
- 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)
- Tumor control or time-to-progression(time of randomization to last follow-up or time of disease progression, 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)
- 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)