Subcutaneous Alemtuzumab Combined With Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allo-SCT in CLL With 17p- or Refractory to Fludarabine
Aims and objectives
- Assessment of the efficacy of the study treatment in the study population in terms of response rate, progression-free survival, failure-free survival and overall survival.
- Acquisition of further data to expand the data base on the toxicity of the study treatment.
- Assessment of the efficacy of the study treatment in biological risk groups.
- Assessment of response in terms of minimal residual disease. Number of patients and estimated duration Total no. of patients: 122 (~29 with 17p deletion for first-line therapy, ~29 with 17p deletion for second- or higher-line treatment, ~65 fludarabine-refractory irrespective of 17p status).
Duration for each patient: Max. 12 weeks of treatment in three 4-week cycles, then up to two years maintenance treatment.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Prospective, Multi-center Phase II Study of Subcutaneous Alemtuzumab Combined With Oral Dexamethasone, Followed by Alemtuzumab Maintenance or Allogeneic Stem-cell Transplantation, in Chronic Lymphocytic Leukemia Which is Associated With 17p Deletion or is Refractory to Fludarabine|
- Response rate [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
Time points for response evaluation according to NCI criteria will be:
- The end of each treatment cycle: after 12 doses (4 weeks actual treatment), 24 doses (8 weeks actual treatment), and 36 doses (12 weeks actual treatment) of alemtuzumab
- During maintenance therapy, every three months
- During follow-up, every three months
- A final response assessment will be made at the end of study treatment if the patient's participation is ended at a point other than one of those specified above.
- Progression-free-survival [ Time Frame: up to five years ] [ Designated as safety issue: No ]Progression-free survival: time from study entry to the detection of progressive disease according to NCI criteria or death of any cause, whichever occurs first.
- Failure-free survival [ Time Frame: up to five years ] [ Designated as safety issue: No ]Failure-free survival: time from study entry until next treatment, detection of progressive disease according to NCI criteria or death of any cause, whichever occurs first.
- Overall survival [ Time Frame: up to five years ] [ Designated as safety issue: No ]Time from study entry to death of any cause.
- Number of participants with Adverse Events as a measure of safety and tolerability [ Time Frame: up to 2.5 years ] [ Designated as safety issue: Yes ]Acquisition of further data to expand the data base on the toxicity of the study treatment. (Type, frequency, severity, timing and relatedness of AEs and laboratory abnormalities observed during different treatment cycles)
|Study Start Date:||February 2008|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
30 mg alemtuzumab will be administered subcutaneously 3 times weekly for 4 weeks (total of 12 doses of 30 mg alemtuzumab) with premedication (as needed) and infection prophylaxis; combined with oral dexamethasone 40 mg total dose for 4 days every 2 weeks; evaluation at end of cycle (i.e. after 12 doses of 30 mg alemtuzumab).
If CR is documented after week 4 (12 doses of 30 mg alemtuzumab) or 8 (24 doses of 30 mg alemtuzumab), maintenance treatment with alemtuzumab or withdrawal from the study and stem cell transplantation will be instituted at this time point.
After a maximum of three 4-week cycles (total of 36 doses of 30 mg alemtuzumab, in case of interruptions this may take longer than 12 weeks), maintenance treatment with alemtuzumab or withdrawal from the study and stem cell transplantation will be instituted. Maintenance treatment with alemtuzumab will continue for a maximum of two years, with evaluation every three months, unless there is PD.
Alemtuzumab 30 mg s.c. 3 × weekly for 28 days (Days 1, 3, 5; 8, 10, 12; etc.)
Show Detailed Description
|Centre Hospitalier de la Côte Basque|
|Bobigny Cedex, France, 93009|
|Hôpital Henri Mondor, Creteil -APHP|
|CRETEIL Cedex, France|
|CHU de Grenoble|
|CHU Claude Huriez|
|Hôpital Edouard Herriot Lyon|
|CHU de Nancy|
|NANCY Cedex, France|
|Hôpital Pitié Salpêtrière Paris-APHP|
|Hôpital Saint-Louis Paris -APHP|
|Centre Hospitalier Marechal Joffre Hôpital Saint-Jean Perpignan|
|PERPIGNAN Cedex, France|
|CHU de Poitiers|
|POITIERS Cedex, France|
|Reims, France, 51092|
|CHU de Tours|
|Charité CBF Berlin|
|University of Cologne|
|Dresden Universtiy Hospital|
|AK St. Georg Hamburg|
|Hannover medical school (MHH)|
|Dr. Soeling Kassel|
|Nuernberg University Hospital|
|Universtiy of Tuebingen|
|University of ulm|
|Ulm, Germany, 89081|
|University Hospital Wuerzburg|
|Dr. Schlag Wuerzburg|
|Principal Investigator:||Stephan Stilgenbauer, Prof Dr med||University of Ulm|