Trial Outcomes & Findings for Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (NCT NCT00935792)

Last Updated: 2017-09-26

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

28 participants

Primary outcome timeframe

After 2 courses of treatment

Results posted on

2017-09-26

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1, Dose Level 1 Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Overall Study STARTED	7	9	12
Overall Study COMPLETED	6	6	12
Overall Study NOT COMPLETED	1	3	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1, Dose Level 1 n=6 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 n=6 Participants Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 n=12 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Total n=24 Participants Total of all reporting groups
Age, Continuous	72.5 years n=5 Participants	73 years n=7 Participants	71 years n=5 Participants	72 years n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants	24 participants n=4 Participants
Previouse number of regimens	2 regimens n=5 Participants	3.5 regimens n=7 Participants	3 regimens n=5 Participants	3 regimens n=4 Participants

PRIMARY outcome

Timeframe: After 2 courses of treatment

Population: All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.

Outcome measures

Outcome measures
Measure	Phase 1, Dose Level 1 n=6 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 n=6 Participants Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 n=12 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Clinical Response (Complete or Partial Remission) Complete Response	0 participants	1 participants	0 participants
Clinical Response (Complete or Partial Remission) Partial Response	3 participants	1 participants	3 participants

PRIMARY outcome

Timeframe: 1 Month

Population: All phase 1 patients are evaluable

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.

Outcome measures

Outcome measures
Measure	Phase 1, Dose Level 1 n=6 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 n=6 Participants Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Number of Participants With Dose-Limiting Toxicities	1 participants with DLTs	2 participants with DLTs	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase 1, Dose Level 1 n=24 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Test the Safety and Tolerability of the Combination of Everolimus and Alemtuzumab.	16 participants	—	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Phase 1, Dose Level 1 n=24 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Survival Time	29.5 Months Interval 11.9 to 36.8	—	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Phase 1, Dose Level 1 n=24 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Progression-free Survival	4.9 Months Interval 3.4 to 8.1	—	—

SECONDARY outcome

Timeframe: up to 5 years

Population: These are 8 patients with verified complete or partial responses(used in primary outcome measure) as well as 2 non verified partial responses.

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

Outcome measures

Outcome measures
Measure	Phase 1, Dose Level 1 n=10 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Duration of Response	4.6 Months Interval 0.7 to 28.4	—	—

SECONDARY outcome

Timeframe: up to 5 years

Outcome measures

Outcome measures
Measure	Phase 1, Dose Level 1 n=24 Participants Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Time to Subsequent Therapy	13.9 Months Interval 5.5 to 26.3	—	—

Adverse Events

Phase 1, Dose Level 1

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Phase 1, Dose Level 2

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Phase 2, Dose Level 1

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1, Dose Level 1 n=7 participants at risk Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 n=9 participants at risk Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 n=12 participants at risk Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Vascular disorders Thrombosis	0.00% 0/7	11.1% 1/9 • Number of events 1	0.00% 0/12

Other adverse events

Other adverse events
Measure	Phase 1, Dose Level 1 n=7 participants at risk Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 1, Dose Level 2 n=9 participants at risk Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Phase 2, Dose Level 1 n=12 participants at risk Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Blood and lymphatic system disorders Febrile neutropenia	14.3% 1/7 • Number of events 1	22.2% 2/9 • Number of events 2	16.7% 2/12 • Number of events 2
Blood and lymphatic system disorders Hemoglobin decreased	71.4% 5/7 • Number of events 7	33.3% 3/9 • Number of events 4	8.3% 1/12 • Number of events 2
Blood and lymphatic system disorders Hemolysis	0.00% 0/7	11.1% 1/9 • Number of events 1	0.00% 0/12
Ear and labyrinth disorders Hearing loss	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 1
Gastrointestinal disorders Abdominal pain	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 2
Gastrointestinal disorders Diarrhea	14.3% 1/7 • Number of events 1	0.00% 0/9	0.00% 0/12
Gastrointestinal disorders Ear, nose and throat examination abnormal	14.3% 1/7 • Number of events 1	0.00% 0/9	16.7% 2/12 • Number of events 2
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 1
Gastrointestinal disorders Oral hemorrhage	0.00% 0/7	11.1% 1/9 • Number of events 1	0.00% 0/12
Gastrointestinal disorders Upper gastrointestinal hemorrhage	14.3% 1/7 • Number of events 1	0.00% 0/9	0.00% 0/12
General disorders Chills	14.3% 1/7 • Number of events 1	0.00% 0/9	0.00% 0/12
General disorders Fatigue	57.1% 4/7 • Number of events 4	33.3% 3/9 • Number of events 3	16.7% 2/12 • Number of events 2
General disorders Fever	57.1% 4/7 • Number of events 8	22.2% 2/9 • Number of events 2	33.3% 4/12 • Number of events 4
Immune system disorders Hypersensitivity	0.00% 0/7	22.2% 2/9 • Number of events 2	0.00% 0/12
Infections and infestations Bladder infection	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 1
Infections and infestations Bronchitis	28.6% 2/7 • Number of events 3	0.00% 0/9	25.0% 3/12 • Number of events 3
Infections and infestations Colitis, infectious (e.g., Clostridium difficile)	14.3% 1/7 • Number of events 1	0.00% 0/9	0.00% 0/12
Infections and infestations Esophageal infection	14.3% 1/7 • Number of events 1	0.00% 0/9	0.00% 0/12
Infections and infestations Mucosal infection	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 1
Infections and infestations Opportunistic infection	14.3% 1/7 • Number of events 2	11.1% 1/9 • Number of events 1	33.3% 4/12 • Number of events 6
Infections and infestations Pharyngitis	14.3% 1/7 • Number of events 2	11.1% 1/9 • Number of events 1	0.00% 0/12
Infections and infestations Pneumonia	14.3% 1/7 • Number of events 3	11.1% 1/9 • Number of events 1	16.7% 2/12 • Number of events 2
Infections and infestations Sepsis	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 1
Infections and infestations Sinusitis	0.00% 0/7	11.1% 1/9 • Number of events 1	0.00% 0/12
Infections and infestations Skin infection	28.6% 2/7 • Number of events 3	0.00% 0/9	8.3% 1/12 • Number of events 1
Infections and infestations Upper respiratory infection	57.1% 4/7 • Number of events 5	22.2% 2/9 • Number of events 3	33.3% 4/12 • Number of events 4
Injury, poisoning and procedural complications Fracture	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 1
Investigations Bilirubin increased	0.00% 0/7	11.1% 1/9 • Number of events 1	0.00% 0/12
Investigations Leukocyte count decreased	71.4% 5/7 • Number of events 7	88.9% 8/9 • Number of events 14	91.7% 11/12 • Number of events 28
Investigations Lymphocyte count decreased	14.3% 1/7 • Number of events 1	55.6% 5/9 • Number of events 12	91.7% 11/12 • Number of events 29
Investigations Neutrophil count decreased	71.4% 5/7 • Number of events 9	55.6% 5/9 • Number of events 9	58.3% 7/12 • Number of events 19
Investigations Platelet count decreased	71.4% 5/7 • Number of events 6	55.6% 5/9 • Number of events 6	41.7% 5/12 • Number of events 9
Metabolism and nutrition disorders Anorexia	14.3% 1/7 • Number of events 1	11.1% 1/9 • Number of events 1	8.3% 1/12 • Number of events 1
Metabolism and nutrition disorders Blood glucose increased	0.00% 0/7	11.1% 1/9 • Number of events 1	0.00% 0/12
Metabolism and nutrition disorders Blood uric acid increased	0.00% 0/7	0.00% 0/9	16.7% 2/12 • Number of events 2
Metabolism and nutrition disorders Dehydration	14.3% 1/7 • Number of events 1	0.00% 0/9	0.00% 0/12
Metabolism and nutrition disorders Serum calcium increased	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 1
Metabolism and nutrition disorders Serum triglycerides increased	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 3
Musculoskeletal and connective tissue disorders Joint pain	14.3% 1/7 • Number of events 1	11.1% 1/9 • Number of events 1	0.00% 0/12
Nervous system disorders Peripheral motor neuropathy	14.3% 1/7 • Number of events 2	0.00% 0/9	0.00% 0/12
Nervous system disorders Peripheral sensory neuropathy	14.3% 1/7 • Number of events 1	0.00% 0/9	0.00% 0/12
Psychiatric disorders Psychosis	0.00% 0/7	0.00% 0/9	8.3% 1/12 • Number of events 2
Respiratory, thoracic and mediastinal disorders Cough	14.3% 1/7 • Number of events 1	11.1% 1/9 • Number of events 1	0.00% 0/12
Respiratory, thoracic and mediastinal disorders Dyspnea	28.6% 2/7 • Number of events 2	0.00% 0/9	0.00% 0/12
Skin and subcutaneous tissue disorders Rash desquamating	14.3% 1/7 • Number of events 1	22.2% 2/9 • Number of events 3	50.0% 6/12 • Number of events 10
Skin and subcutaneous tissue disorders Sweating	14.3% 1/7 • Number of events 1	0.00% 0/9	8.3% 1/12 • Number of events 2

Additional Information

Timothy Call, M.D.

Mayo Clinic

Phone: 5076682050

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place