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Trial record 67 of 495 for:    LENALIDOMIDE AND every 28 days

Study of Lenalidomide in Previously Untreated, Symptomatic Chronic Lymphocytic Leukemia (CLL) (Rev-CLL)

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ClinicalTrials.gov Identifier: NCT00751296
Recruitment Status : Terminated (Seven years of follow-up & final analysis done in Dec 2012.)
First Posted : September 11, 2008
Results First Posted : May 12, 2016
Last Update Posted : June 16, 2016
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
University Health Network, Toronto

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Lymphocytic Leukaemia
Intervention Drug: Lenalidomide
Enrollment 27
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Lenalidiomide
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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.

Period Title: Overall Study
Started 27 [1]
Completed 25
Not Completed 2
Reason Not Completed
Adverse Event             2
[1]
The start date of the study was 25 August 2006.
Arm/Group Title Lenalidiomide
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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).

Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
<=18 years
0
   0.0%
Between 18 and 65 years
17
  68.0%
>=65 years
8
  32.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 25 participants
60
(33 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
9
  36.0%
Male
16
  64.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Canada Number Analyzed 25 participants
25
1.Primary Outcome
Title To Assess the Efficacy (Response Rate) of Oral Lenalidomide in the Treatment of Patients With Symptomatic, Previously Untreated, Chronic Lymphocytic Leukemia (CLL)
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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).

Time Frame 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.
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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.
Arm/Group Title Lenalidiomide
Hide Arm/Group Description:

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 Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
Complete response 5
Partial response 13
Stable Disease 6
2.Secondary Outcome
Title Percentage of Participants With Progression-free Survival (PFS) and Overall Survival (OS).
Hide Description 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)).
Time Frame 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.
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lenalidiomide
Hide Arm/Group Description:

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 Number of Participants Analyzed 25
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Overall survival
85.3
(71.1 to 100)
Progression free survival
64.6
(47.5 to 87.8)
Time Frame [Not Specified]
Adverse Event Reporting Description CTCAE Version 3.0 was used for adverse event grading and categorizing
 
Arm/Group Title Lenalidiomide
Hide Arm/Group Description

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.

All-Cause Mortality
Lenalidiomide
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Lenalidiomide
Affected / at Risk (%) # Events
Total   17/25 (68.00%)    
Blood and lymphatic system disorders   
Febrile Neutropenia   4/25 (16.00%)  4
Cardiac disorders   
Coronary Artery disease   1/25 (4.00%)  1
Atrial Fibrillation   1/25 (4.00%)  1
General disorders   
Fever   1/25 (4.00%)  1
Infections and infestations   
Disseminated Zoster   1/25 (4.00%)  1
Community Acquired pneumonia   1/25 (4.00%)  1
Ear infection   1/25 (4.00%)  1
Bacteremia   1/25 (4.00%)  1
Injury, poisoning and procedural complications   
Fracture  1  1/25 (4.00%)  1
Investigations   
Thrombocytopenia   2/25 (8.00%)  2
Cytopenias   1/25 (4.00%)  1
Metabolism and nutrition disorders   
Diabetic Ketoacidosis   1/25 (4.00%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
In-situ Squamous cell carcinoma   2/25 (8.00%)  2
Relapse of lung cancer   1/25 (4.00%)  1
Basal Cell Carcinoma   1/25 (4.00%)  1
Endometrial adenocarcinoma   1/25 (4.00%)  1
Respiratory, thoracic and mediastinal disorders   
Cough   1/25 (4.00%)  1
Skin and subcutaneous tissue disorders   
Skin Rash   1/25 (4.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, Fracture after fall
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Lenalidiomide
Affected / at Risk (%) # Events
Total   25/25 (100.00%)    
Blood and lymphatic system disorders   
Tumor Flare  1 [1]  22/25 (88.00%) 
Leg edema  [1]  3/25 (12.00%) 
Febrile Neutropenia  [1]  1/25 (4.00%) 
Anemia  [1]  6/25 (24.00%) 
Gastrointestinal disorders   
Diarrhea  [1]  8/25 (32.00%) 
Constipation  [1]  6/25 (24.00%) 
General disorders   
Fatigue  1 [1]  18/25 (72.00%) 
Infections and infestations   
Skin infection  1 [1]  4/25 (16.00%) 
Upper Respiratory/Sinus infection  1 [1]  2/25 (8.00%) 
Investigations   
Elevated Creatinine  1 [1]  11/25 (44.00%) 
Hypocalcemia  [1]  11/25 (44.00%) 
Hypokalemia  [1]  10/25 (40.00%) 
Hypophosphatemia  [1]  10/25 (40.00%) 
Elevated AST or ALT  [1]  9/25 (36.00%) 
Hypernatremia  [1]  5/25 (20.00%) 
Hyponatremia  [1]  4/25 (16.00%) 
Neutropenia  [1]  18/25 (72.00%) 
Thrombocytopenia  [1]  7/25 (28.00%) 
Musculoskeletal and connective tissue disorders   
Myalgia  [1]  10/25 (40.00%) 
Generalized Muscle weakness  [1]  3/25 (12.00%) 
Nervous system disorders   
Sensory neuropathy  [1]  4/25 (16.00%) 
Dizziness  [1]  3/25 (12.00%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea  [1]  3/25 (12.00%) 
Skin and subcutaneous tissue disorders   
Rash  [1]  15/25 (60.00%) 
Pruritus  [1]  8/25 (32.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE Version 3.0
[1]
Drug related
Original study protocol used a starting lenalidomide dose of 10mg OD for 21days of a 28-day cycle, escalating weekly by 5mg to a target of 25mg daily. Toxicities reported with the first two enrolled patients lead to the current protocol amendment.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Christine Chen
Organization: University Health Network - Princess Margaret Cancer Centre
Phone: 416-946-2827
EMail: Christine.Chen@uhn.ca
Layout table for additonal information
Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00751296     History of Changes
Other Study ID Numbers: Rev-06-0099
RV-CLL-PI-0099 ( Other Identifier: Study sponsor )
First Submitted: September 10, 2008
First Posted: September 11, 2008
Results First Submitted: December 29, 2015
Results First Posted: May 12, 2016
Last Update Posted: June 16, 2016