Trial Outcomes & Findings for Study of Lenalidomide in Previously Untreated, Symptomatic Chronic Lymphocytic Leukemia (CLL) (NCT NCT00751296)
NCT ID: NCT00751296
Last Updated: 2016-06-16
Results Overview
The primary endpoint was objective response to lenalidomide (Complete response +Partial response) evaluated as per the revised 1996 National Cancer Institute Working Group Guidelines. Complete response: absence of lymphadenopathy and organomegaly by physical exam and radiology, absence of constitutional symptoms, normal CBC. Bone marrow to be done 2 months after the above criteria are met, must be normocellular, with \<30% lymphocytes. Partial Response: ≥ 50% decrease in the peripheral blood lymphocytes from pre-treatment value, ≥ 50% reduction in lymphadenopathy and organomegaly by physical exam or on CT scan. one or more of the following: neutrophils ≥ 1.5 x109/L, platelets \> 100 x109/L or 50% improvement over baseline, hemoglobin \> 110 g/L or 50% improvement over baseline (without transfusion).
TERMINATED
PHASE2
27 participants
Patients will be treated with lenalidomide until disease progression or 2 cycles past CR (no maximum of cycles). Participants were followed upto 53.2 months for the final data analysis.
2016-06-16
Participant Flow
This was a single site, Investigator initiated study. Patients gave informed consent according to institutional and university human experimentation committee requirements. Previously untreated B-cell CLL patients \>/= 18 years of age were eligible if they met the eligibility criteria.
Study was halted and the protocol amended after severe toxicities were noted in the first 2 study patients when they were dosed as per the initial protocol dosing guidelines. Their data was not included in the analysis and additional 25 eligible patients were enrolled and their data was analyzed.
Participant milestones
| Measure |
Lenalidiomide
Lenalidomide target dose of 10 mg PO OD X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28-day cycle.
Lenalidomide: Subjects will receive lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle. Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).
Dose escalation beyond 10 mg daily to a maximum of 25 mgs daily was permitted for nonresponders.
|
|---|---|
|
Overall Study
STARTED
|
27
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Lenalidiomide
Lenalidomide target dose of 10 mg PO OD X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28-day cycle.
Lenalidomide: Subjects will receive lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle. Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).
Dose escalation beyond 10 mg daily to a maximum of 25 mgs daily was permitted for nonresponders.
|
|---|---|
|
Overall Study
Adverse Event
|
2
|
Baseline Characteristics
Study of Lenalidomide in Previously Untreated, Symptomatic Chronic Lymphocytic Leukemia (CLL)
Baseline characteristics by cohort
| Measure |
Lenalidiomide
n=25 Participants
Lenalidomide target dose of 10 mg PO OD X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28-day cycle.
Lenalidomide: Subjects will receive lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle. Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
8 Participants
n=5 Participants
|
|
Age, Continuous
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
25 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Patients will be treated with lenalidomide until disease progression or 2 cycles past CR (no maximum of cycles). Participants were followed upto 53.2 months for the final data analysis.Population: Severe toxicities were seen in the first two patients enrolled on the initial protocol. The study was halted and the protocol amended to use a starting dose of lenalidomide 2.5 mg with monthly escalations to a target dose of 10 mg, extended tumor lysis prophylaxis and monitoring. 25 response evaluable patients were enrolled on the amended protocol.
The primary endpoint was objective response to lenalidomide (Complete response +Partial response) evaluated as per the revised 1996 National Cancer Institute Working Group Guidelines. Complete response: absence of lymphadenopathy and organomegaly by physical exam and radiology, absence of constitutional symptoms, normal CBC. Bone marrow to be done 2 months after the above criteria are met, must be normocellular, with \<30% lymphocytes. Partial Response: ≥ 50% decrease in the peripheral blood lymphocytes from pre-treatment value, ≥ 50% reduction in lymphadenopathy and organomegaly by physical exam or on CT scan. one or more of the following: neutrophils ≥ 1.5 x109/L, platelets \> 100 x109/L or 50% improvement over baseline, hemoglobin \> 110 g/L or 50% improvement over baseline (without transfusion).
Outcome measures
| Measure |
Lenalidiomide
n=25 Participants
Lenalidomide target dose of 10 mg PO OD X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28-day cycle.
Lenalidomide: Subjects will receive lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle. Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).
Dose escalation beyond 10 mg daily to a maximum of 25 mgs daily was permitted for nonresponders.
|
|---|---|
|
To Assess the Efficacy (Response Rate) of Oral Lenalidomide in the Treatment of Patients With Symptomatic, Previously Untreated, Chronic Lymphocytic Leukemia (CLL)
Complete response
|
5 participants
|
|
To Assess the Efficacy (Response Rate) of Oral Lenalidomide in the Treatment of Patients With Symptomatic, Previously Untreated, Chronic Lymphocytic Leukemia (CLL)
Partial response
|
13 participants
|
|
To Assess the Efficacy (Response Rate) of Oral Lenalidomide in the Treatment of Patients With Symptomatic, Previously Untreated, Chronic Lymphocytic Leukemia (CLL)
Stable Disease
|
6 participants
|
SECONDARY outcome
Timeframe: Patients will be treated with lenalidomide until disease progression or 2 cycles past CR (no maximum of cycles). Participants were followed upto 53.2 months for the final data analysis.Assess the time to disease progression and overall survival. (Progressive disease is defined as at least one of the following: more than or equal to 50% increase in the sum of the products of the greatest diameters of at least 2 lymph nodes on 2 consecutive determinations 2 weeks apart (at least one node must be ≥ 2 cm) or new palpable lymph nodes, more than or equal to 50% increase in the size of the liver and/or spleen as determined by measurement below the costal margin or appearance of palpable hepatomegaly or splenomegaly not previously present, more than or equal to 50% increase in the absolute number of circulating lymphocytes to at least 5.0 x109/L, OR transformation to a more aggressive histology (e.g. Richter's syndrome or prolymphocytic leukemia with \>55% prolymphocytes)).
Outcome measures
| Measure |
Lenalidiomide
n=25 Participants
Lenalidomide target dose of 10 mg PO OD X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28-day cycle.
Lenalidomide: Subjects will receive lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle. Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).
Dose escalation beyond 10 mg daily to a maximum of 25 mgs daily was permitted for nonresponders.
|
|---|---|
|
Percentage of Participants With Progression-free Survival (PFS) and Overall Survival (OS).
Overall survival
|
85.3 percentage of participants
Interval 71.1 to 100.0
|
|
Percentage of Participants With Progression-free Survival (PFS) and Overall Survival (OS).
Progression free survival
|
64.6 percentage of participants
Interval 47.5 to 87.8
|
Adverse Events
Lenalidiomide
Serious adverse events
| Measure |
Lenalidiomide
n=25 participants at risk
Lenalidomide target dose of 10 mg PO OD X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28-day cycle.
Lenalidomide: Subjects will receive lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle. Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).
Dose escalation beyond 10 mg daily to a maximum of 25 mgs daily was permitted for nonresponders.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
16.0%
4/25 • Number of events 4
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Infections and infestations
Disseminated Zoster
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Cardiac disorders
Coronary Artery disease
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Cardiac disorders
Atrial Fibrillation
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
General disorders
Fever
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
In-situ Squamous cell carcinoma
|
8.0%
2/25 • Number of events 2
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Thrombocytopenia
|
8.0%
2/25 • Number of events 2
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Infections and infestations
Community Acquired pneumonia
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Infections and infestations
Ear infection
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Infections and infestations
Bacteremia
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Injury, poisoning and procedural complications
Fracture
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Metabolism and nutrition disorders
Diabetic Ketoacidosis
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Cytopenias
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Relapse of lung cancer
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Skin and subcutaneous tissue disorders
Skin Rash
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma
|
4.0%
1/25 • Number of events 1
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
Other adverse events
| Measure |
Lenalidiomide
n=25 participants at risk
Lenalidomide target dose of 10 mg PO OD X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28-day cycle.
Lenalidomide: Subjects will receive lenalidomide, starting at 2.5 mg daily x 3 weeks (days 1-21) and escalating up to a target dose of 10 mg daily X 3 weeks (days 1-21) followed by 1 week off therapy (days 22-28) on a 28 day cycle. Patients will be treated with lenalidomide until disease progression or 2 cycles past CR. (no maximum of cycles).
Dose escalation beyond 10 mg daily to a maximum of 25 mgs daily was permitted for nonresponders.
|
|---|---|
|
Blood and lymphatic system disorders
Tumor Flare
|
88.0%
22/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
General disorders
Fatigue
|
72.0%
18/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Skin and subcutaneous tissue disorders
Rash
|
60.0%
15/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
40.0%
10/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
32.0%
8/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Gastrointestinal disorders
Diarrhea
|
32.0%
8/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Gastrointestinal disorders
Constipation
|
24.0%
6/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Nervous system disorders
Sensory neuropathy
|
16.0%
4/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Blood and lymphatic system disorders
Leg edema
|
12.0%
3/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Nervous system disorders
Dizziness
|
12.0%
3/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Musculoskeletal and connective tissue disorders
Generalized Muscle weakness
|
12.0%
3/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
12.0%
3/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Elevated Creatinine
|
44.0%
11/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Hypocalcemia
|
44.0%
11/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Hypokalemia
|
40.0%
10/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Hypophosphatemia
|
40.0%
10/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Elevated AST or ALT
|
36.0%
9/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Hypernatremia
|
20.0%
5/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Hyponatremia
|
16.0%
4/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
4.0%
1/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Infections and infestations
Skin infection
|
16.0%
4/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Neutropenia
|
72.0%
18/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Blood and lymphatic system disorders
Anemia
|
24.0%
6/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Investigations
Thrombocytopenia
|
28.0%
7/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
|
Infections and infestations
Upper Respiratory/Sinus infection
|
8.0%
2/25
CTCAE Version 3.0 was used for adverse event grading and categorizing
|
Additional Information
Dr. Christine Chen
University Health Network - Princess Margaret Cancer Centre
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60