Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the signaling molecules needed for cell growth. Monoclonal antibodies, such as alemtuzumab, can bind to and kill malignant lymphocytes.
PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with alemtuzumab and will see how well they work in treating patients with recurrent chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL).
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Everolimus (RAD001) and Alemtuzumab: A Phase I/II Study|
- Clinical Response (Complete or Partial Remission) [ Time Frame: After 2 courses of treatment ]CR requires all of the following for a period of at least 2months:Absence of lymphadenopathy.No hepatomegaly or splenomegaly.Absence of constitutional symptoms.• Neutrophils>1500/ul•Platelets>100,000/ul • Hemoglobin >11.0gm/dl• Peripheral blood lymphocytes <4000/uLBonemarrow. normocellular with<30%of nucleated cells being lymphocytes.PR requires two for 2+months.≥50%decrease in peripheral blood lymphocyte count from the pretreatment baseline value.≥ 50%reduction in the sum of the products of the maximal perpendicular diameters of the largest measured node or nodal masses in the right and left cervical, axillary, and inguinal lymph node regions.≥ 50%reduction in size of liver and/or spleen noting the maximal distance below the respective costal margins of palpable hepatosplenomegaly during rest.Neutrophils>1500/ul or50%improvement over baseline. Platelets>100,000/ul or50%increase over baseline. Hemoglobin>11.0 gm/dl or50%increase over baseline without transfusions
- Number of Participants With Dose-Limiting Toxicities [ Time Frame: 1 Month ]
The maximum tolerated dose is the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. Dose-limiting toxicity will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria.
Hematologic: ANC ≤ 0.3 x 109/L or platelet count < 10 x 109/L Other nonhematologic: ≥grade 3 as per NCI Common Terminology Criteria for Adverse Events v3.0 except for fatigue, hyperlipidemia, and hyperglycemia.
- Test the Safety and Tolerability of the Combination of Everolimus and Alemtuzumab. [ Time Frame: Up to 12 months past final treatment ]The number and severity of all adverse events will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group. Below is the number of patients that experienced a grade 3+ Adverse event that was at least possibly related to Treatment.
- Survival Time [ Time Frame: up to 5 years ]Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier
- Progression-free Survival [ Time Frame: up to 5 years ]Progression-free survival time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier
- Duration of Response [ Time Frame: up to 5 years ]Duration of response is defined for all evaluable patients who have achieved a clinical response as the date at which the patient's objective status is first noted to be a Complete Response or Partial Response to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier
- Time to Subsequent Therapy [ Time Frame: up to 5 years ]
|Study Start Date:||July 2009|
|Study Completion Date:||December 2015|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Other Names:Drug: everolimus
Please refer to this study by its ClinicalTrials.gov identifier: NCT00935792
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Clive S. Zent, M.D.||Mayo Clinic|
|Principal Investigator:||Jose F. Leis, M.D.||Mayo Clinic|