Alemtuzumab and CHOP Chemotherapy for Aggressive Histological Peripheral T-Cell Lymphomas (ACCAPELA)
The primary objectives of this study are to:
- establish the safety and dose limiting toxicities of combining alemtuzumab with CHOP chemotherapy for patients with newly diagnosed aggressive T-cell lymphomas; and
- to measure the pharmacokinetics of alemtuzumab used in different subcutaneous doses and schedules.
This will then determine the dose with the highest achievable drug levels with acceptable toxicities worthy of further investigation.
The secondary objectives are to:
- establish the efficacy of combination alemtuzumab with CHOP chemotherapy; and
- to measure the effects of combination alemtuzumab with CHOP chemotherapy on T-cell reconstitution and cytomegalovirus (CMV) reactivation.
Peripheral T-cell Lymphomas
Drug: Alemtuzumab (Campath-1H)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Alemtuzumab and CHOP Chemotherapy for Aggressive Histological Peripheral T-Cell Lymphomas: A Multi-centre Phase I and II Study|
- toxicity [ Time Frame: 8 cycles of treatment ] [ Designated as safety issue: Yes ]
- efficacy [ Time Frame: Post cycle 3 and Post cycle 8 ] [ Designated as safety issue: Yes ]
- tumour response [ Time Frame: Post Cycle 3 and Post Cycle 8 Q 6 months in Followup ] [ Designated as safety issue: Yes ]
- pharmacokinetic analysis [ Time Frame: Day 1 of 8 Cycles of treatment and Post Last Dose on Day 3,6,10,13 ] [ Designated as safety issue: Yes ]
- immunological monitoring [ Time Frame: Baseline Day 1 On Treatment Day 1 Cycle 4 and Cycle 8 and 6 months Follow-up ] [ Designated as safety issue: No ]
|Study Start Date:||September 2006|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Drug: Alemtuzumab (Campath-1H)
Aggressive peripheral T-cell lymphomas account for 10 - 15% of all Non-Hodgkin's Lymphoma (NHL) and present with more adverse prognostic features than aggressive histology B-cell NHL . Correspondingly, they have an overall poorer prognosis than B-cell lymphomas, achieving lower complete response rates, freedom from progression and overall survival with conventional anthracycline-based CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. Fewer than 30% of patients are cured with therapy. New treatments that replicate the improved survivals with chemo-immunotherapy for B-cell lymphomas are needed. Alemtuzumab is a humanized murine antibody that binds to a ubiquitous lymphoid marker CD52 and is efficacious (as monotherapy) in related lymphoproliferative diseases. Combining alemtuzumab with CHOP chemotherapy may improve the response rates and outcomes of patients with this sub-type of NHL. The combination must be first tested in a dose escalation fashion to establish the dosage of the doublet because of the potential for overlapping or exaggerated toxicities.
This prospective, multi-center, open label Phase I-II study will enroll 22-84 patients with newly diagnosed previously untreated aggressive histology peripheral T-cell lymphomas. In the Phase I component, patients will be sequentially enrolled in cohorts of three patients and treated with increasing doses of alemtuzumab administered in combination with standard CHOP chemotherapy. When the maximal tolerated dose is determined, this dose and schedule will then be tested in up to 46 patients using a Simon two stage Phase II design.
|Canada, British Columbia|
|St. Paul's Hospital|
|Vancouver, British Columbia, Canada, V6Z 1Y6|
|Juravinski Cancer Centre|
|Hamilton, Ontario, Canada, L8V 5C2|
|London Health Sciences Centre|
|London, Ontario, Canada, N6A 4G5|
|Sunnybrook Health Sciences Centre, Odette Cancer Centre|
|Toronto, Ontario, Canada, M4N 3M5|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Rena Buckstein, MD||Sunnybrook Health Sciences Centre, Odette Cancer Centre|