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Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

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ClinicalTrials.gov Identifier: NCT00935792
Recruitment Status : Completed
First Posted : July 9, 2009
Results First Posted : December 12, 2016
Last Update Posted : September 26, 2017
Sponsor:
Information provided by (Responsible Party):
Mayo Clinic

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphocytic Leukemia
Interventions Drug: alemtuzumab
Drug: everolimus
Enrollment 28
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1, Dose Level 1 Phase 1, Dose Level 2 Phase 2, Dose Level 1
Hide Arm/Group Description Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks. Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks. Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Period Title: Overall Study
Started 7 9 12
Completed 6 6 12
Not Completed 1 3 0
Arm/Group Title Phase 1, Dose Level 1 Phase 1, Dose Level 2 Phase 2, Dose Level 1 Total
Hide Arm/Group Description Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks. Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks. Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 6 6 12 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 12 participants 24 participants
72.5
(66 to 78)
73
(54 to 82)
71
(61 to 82)
72
(54 to 82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants 24 participants
Female
4
  66.7%
4
  66.7%
4
  33.3%
12
  50.0%
Male
2
  33.3%
2
  33.3%
8
  66.7%
12
  50.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 6 participants 12 participants 24 participants
6 6 12 24
Previouse number of regimens  
Median (Full Range)
Unit of measure:  Regimens
Number Analyzed 6 participants 6 participants 12 participants 24 participants
2
(1 to 6)
3.5
(1 to 5)
3
(1 to 10)
3
(1 to 10)
1.Primary Outcome
Title Clinical Response (Complete or Partial Remission)
Hide Description 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
Time Frame After 2 courses of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.
Arm/Group Title Phase 1, Dose Level 1 Phase 1, Dose Level 2 Phase 2, Dose Level 1
Hide Arm/Group Description:
Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Overall Number of Participants Analyzed 6 6 12
Measure Type: Number
Unit of Measure: participants
Complete Response 0 1 0
Partial Response 3 1 3
2.Primary Outcome
Title Number of Participants With Dose-Limiting Toxicities
Hide Description

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.

Time Frame 1 Month
Hide Outcome Measure Data
Hide Analysis Population Description
All phase 1 patients are evaluable
Arm/Group Title Phase 1, Dose Level 1 Phase 1, Dose Level 2
Hide Arm/Group Description:
Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Overall Number of Participants Analyzed 6 6
Measure Type: Number
Unit of Measure: participants with DLTs
1 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 1, Dose Level 1, Phase 1, Dose Level 2
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Other Statistical Analysis Estimated maximum tolerated dose was 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
3.Primary Outcome
Title Test the Safety and Tolerability of the Combination of Everolimus and Alemtuzumab.
Hide Description 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.
Time Frame Up to 12 months past final treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Evaluable Patients
Hide Arm/Group Description:
Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
16
4.Secondary Outcome
Title Survival Time
Hide Description 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
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Evaluable Patients
Hide Arm/Group Description:
Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Overall Number of Participants Analyzed 24
Median (95% Confidence Interval)
Unit of Measure: Months
29.5
(11.9 to 36.8)
5.Secondary Outcome
Title Progression-free Survival
Hide Description 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
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Evaluable Patients
Hide Arm/Group Description:
Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Overall Number of Participants Analyzed 24
Median (95% Confidence Interval)
Unit of Measure: Months
4.9
(3.4 to 8.1)
6.Secondary Outcome
Title Duration of Response
Hide Description 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 Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
These are 8 patients with verified complete or partial responses(used in primary outcome measure) as well as 2 non verified partial responses.
Arm/Group Title All Evaluable Patients
Hide Arm/Group Description:
Patients are only evaluable for duration of response when they have already been noted as a complete response or partial response.
Overall Number of Participants Analyzed 10
Median (95% Confidence Interval)
Unit of Measure: Months
4.6
(.7 to 28.4)
7.Secondary Outcome
Title Time to Subsequent Therapy
Hide Description [Not Specified]
Time Frame up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Evaluable Patients
Hide Arm/Group Description:
Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Overall Number of Participants Analyzed 24
Median (95% Confidence Interval)
Unit of Measure: Months
13.9
(5.5 to 26.3)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase 1, Dose Level 1 Phase 1, Dose Level 2 Phase 2, Dose Level 1
Hide Arm/Group Description Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks. Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks. Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
All-Cause Mortality
Phase 1, Dose Level 1 Phase 1, Dose Level 2 Phase 2, Dose Level 1
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1, Dose Level 1 Phase 1, Dose Level 2 Phase 2, Dose Level 1
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/7 (0.00%)      1/9 (11.11%)      0/12 (0.00%)    
Vascular disorders       
Thrombosis  1  0/7 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase 1, Dose Level 1 Phase 1, Dose Level 2 Phase 2, Dose Level 1
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/7 (100.00%)      8/9 (88.89%)      12/12 (100.00%)    
Blood and lymphatic system disorders       
Febrile neutropenia  1  1/7 (14.29%)  1 2/9 (22.22%)  2 2/12 (16.67%)  2
Hemoglobin decreased  1  5/7 (71.43%)  7 3/9 (33.33%)  4 1/12 (8.33%)  2
Hemolysis  1  0/7 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Ear and labyrinth disorders       
Hearing loss  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Gastrointestinal disorders       
Abdominal pain  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  2
Diarrhea  1  1/7 (14.29%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Ear, nose and throat examination abnormal  1  1/7 (14.29%)  1 0/9 (0.00%)  0 2/12 (16.67%)  2
Gastrointestinal disorder  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Oral hemorrhage  1  0/7 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Upper gastrointestinal hemorrhage  1  1/7 (14.29%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
General disorders       
Chills  1  1/7 (14.29%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Fatigue  1  4/7 (57.14%)  4 3/9 (33.33%)  3 2/12 (16.67%)  2
Fever  1  4/7 (57.14%)  8 2/9 (22.22%)  2 4/12 (33.33%)  4
Immune system disorders       
Hypersensitivity  1  0/7 (0.00%)  0 2/9 (22.22%)  2 0/12 (0.00%)  0
Infections and infestations       
Bladder infection  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Bronchitis  1  2/7 (28.57%)  3 0/9 (0.00%)  0 3/12 (25.00%)  3
Colitis, infectious (e.g., Clostridium difficile)  1  1/7 (14.29%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Esophageal infection  1  1/7 (14.29%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Mucosal infection  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Opportunistic infection  1  1/7 (14.29%)  2 1/9 (11.11%)  1 4/12 (33.33%)  6
Pharyngitis  1  1/7 (14.29%)  2 1/9 (11.11%)  1 0/12 (0.00%)  0
Pneumonia  1  1/7 (14.29%)  3 1/9 (11.11%)  1 2/12 (16.67%)  2
Sepsis  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Sinusitis  1  0/7 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Skin infection  1  2/7 (28.57%)  3 0/9 (0.00%)  0 1/12 (8.33%)  1
Upper respiratory infection  1  4/7 (57.14%)  5 2/9 (22.22%)  3 4/12 (33.33%)  4
Injury, poisoning and procedural complications       
Fracture  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Investigations       
Bilirubin increased  1  0/7 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Leukocyte count decreased  1  5/7 (71.43%)  7 8/9 (88.89%)  14 11/12 (91.67%)  28
Lymphocyte count decreased  1  1/7 (14.29%)  1 5/9 (55.56%)  12 11/12 (91.67%)  29
Neutrophil count decreased  1  5/7 (71.43%)  9 5/9 (55.56%)  9 7/12 (58.33%)  19
Platelet count decreased  1  5/7 (71.43%)  6 5/9 (55.56%)  6 5/12 (41.67%)  9
Metabolism and nutrition disorders       
Anorexia  1  1/7 (14.29%)  1 1/9 (11.11%)  1 1/12 (8.33%)  1
Blood glucose increased  1  0/7 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Blood uric acid increased  1  0/7 (0.00%)  0 0/9 (0.00%)  0 2/12 (16.67%)  2
Dehydration  1  1/7 (14.29%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Serum calcium increased  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Serum triglycerides increased  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  3
Musculoskeletal and connective tissue disorders       
Joint pain  1  1/7 (14.29%)  1 1/9 (11.11%)  1 0/12 (0.00%)  0
Nervous system disorders       
Peripheral motor neuropathy  1  1/7 (14.29%)  2 0/9 (0.00%)  0 0/12 (0.00%)  0
Peripheral sensory neuropathy  1  1/7 (14.29%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Psychiatric disorders       
Psychosis  1  0/7 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  2
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/7 (14.29%)  1 1/9 (11.11%)  1 0/12 (0.00%)  0
Dyspnea  1  2/7 (28.57%)  2 0/9 (0.00%)  0 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders       
Rash desquamating  1  1/7 (14.29%)  1 2/9 (22.22%)  3 6/12 (50.00%)  10
Sweating  1  1/7 (14.29%)  1 0/9 (0.00%)  0 1/12 (8.33%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Timothy Call, M.D.
Organization: Mayo Clinic
Phone: 5076682050
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00935792     History of Changes
Other Study ID Numbers: MC088C
MC088C ( Other Identifier: Mayo Clinic Cancer Center )
NCI-2009-00935 ( Registry Identifier: NCI's CTRO )
08-008775 ( Other Identifier: Mayo Clinic IRB )
First Submitted: July 6, 2009
First Posted: July 9, 2009
Results First Submitted: April 29, 2016
Results First Posted: December 12, 2016
Last Update Posted: September 26, 2017