Weekly Subcutaneous Alemtuzumab and Rituximab for Relapsed CLL
The purpose of this study is to determine whether the combination of alemtuzumab and rituximab is safe and effective in treating patients with relapsed Chronic Lymphocytic Leukemia (CLL) and to determine whether alemtuzumab can be given as a single weekly subcutaneous dose, together with rituximab.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Weekly Subcutaneous Alemtuzumab and Rituximab for Relapsed CLL|
- Maximum tolerated dose of alemtuzumab given once weekly [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Response rate of combined rituximab and subcutaneous alemtuzumab (complete or partial response) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Dose limiting toxicities defined as non-hematologic toxicity of grade 3 or greater or irreversible grade 2 renal, neurologic or cardiac toxicity or infectious toxicities if grade 4 or greater [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Dose limiting toxicities defined as hematologic toxicities of grade 3 or greater neutropenia or thrombocytopenia for greater than 2 weeks OR ANC < 250 or platelets < 20,000 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Response rate as measured by Chest/abdominal/pelvic (+/- neck) CT 4 to 8 weeks following conclusion of 8 Weeks of therapy or at time of study withdrawal [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Response rate as measured by physical exam of lymph nodes at 4 to 8 weeks following conclusion of 8 Weeks of therapy or at time of study withdrawal, then every 3 months until disease progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||May 2006|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Alemtuzumab & Rituximab
Alemtuzumab Dosage will vary during Phase I of trial: Given intravenously on days 1, 3, and 5 for weeks one and two, on days 1 and 4 for weeks three and four and on day 1 for weeks five through eight. Participants may receive either one eight-week course of treatment or two eight-week courses of treatment (16 weeks)
Rituximab- Given intravenously on day 1 of every week for eight weeks (or 16 weeks)
Given intravenously on day 1 of every week for eight weeks (or 16 weeks)Drug: Alemtuzumab
Drug: Alemtuzumab Dosage will vary during Phase I of trial: Given intravenously on days 1, 3, and 5 for weeks one and two, on days 1 and 4 for weeks three and four and on day 1 for weeks five through eight. Participants may receive either one eight-week course of treatment or two eight-week courses of treatment (16 weeks).
This study proposes to combine alemtuzumab, which effectively treats peripheral blood and bone marrow disease in CLL, with rituximab, which has activity in lymph node disease, in a streamlined and convenient administration schedule. Preclinical data support synergistic interaction of the two. The primary objectives are (1) to determine the overall and complete response (CR) rate in patients with relapsed CLL and to determine the safety of the combination, and (2) the safety of higher doses of alemtuzumab at less frequent intervals. Secondary objectives are (1) to describe the duration of response, progression-free survival, and overall survival in patients not proceeding to allo transplant, (2) to determine the improvement in overall and complete response associated with administration of a 2nd eight week course of therapy, and (3) to assess minimal residual disease in certain patients and to correlate those results with survival. If at least 16 responses are observed among 35 patients, then the treatment will be considered promising.
The development of antibody therapies has held promise for CLL, since CLL therapies have been palliative, with no established therapy shown to improve survival. Studies have suggested that in contrast to what is seen with fludarabine and alkylating agents, response rates to alemtuzumab are maintained in CLL subjects with P53 mutations. Tolerability of rituximab and its major activity in nodes make it an attractive candidate for combination with alemtuzumab.
This is a single center (DF/HCC), single arm, multi cohort, phase I study, with treatment on an outpatient basis. If the initial alemtuzumab dose of 30 mg sc d1, 3,and 5 is tolerated, there will be dose escalations in cohorts of 3, up to 90 mg d1 per week. Following determination of a maximum tolerated dose, accrual of all remaining patients will occur at that dose. Subjects will be restaged after 8 weeks of therapy, and may proceed to transplant. If deriving benefit, but not in CR, subjects may receive another 8 weeks of therapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00330252
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Jennifer R Brown, MD, PhD||Dana-Farber Cancer Institute|