Trial Outcomes & Findings for Alternating Thalidomide and Lenalidomide Therapy Plus Rituximab (ThRiL) as Initial Treatment for Patients With CLL (NCT NCT01125176)

Last Updated: 2022-01-21

Results Overview

Response will be evaluated in this study using the International Workshop on CLL (IWCLL) update of the 1996 NCI-Working Group criteria for CLL, which includes assessment of the following: clonal lymphocytes in the peripheral blood by flow cytometry, blood tests for neutrophil count, hemoglobin, and platelet count, CT examination for lymphadenopathy, hepatomegaly, splenomegaly, constitutional symptoms, bone marrow assessment via biopsy/aspirate, and evaluation for disease transformation.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

From date of study drug initiation until date of best response, assessed up to 6 years.

Results posted on

2022-01-21

Participant Flow

Participants were accrued to the study at Weill Cornell Medical College between March 2012 and September 2013.

One participant was deemed ineligible for the study following the completion of the informed consent process.

Participant milestones

Participant milestones
Measure	All Subjects In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) Thalidomide: 50 mg oral dosing every other day Lenalidomide: varying oral doses every other day (max 25 mg/day) Rituximab: 375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Treatment Phase STARTED	14
Treatment Phase COMPLETED	13
Treatment Phase NOT COMPLETED	1
Post-treatment Follow-up Phase STARTED	13
Post-treatment Follow-up Phase COMPLETED	2
Post-treatment Follow-up Phase NOT COMPLETED	11

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Alternating Thalidomide and Lenalidomide Therapy Plus Rituximab (ThRiL) as Initial Treatment for Patients With CLL

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Subjects n=14 Participants In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) Thalidomide: 50 mg oral dosing every other day Lenalidomide: varying oral doses every other day (max 25 mg/day) Rituximab: 375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Age, Categorical <=18 years	0 Participants n=39 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=39 Participants
Age, Categorical >=65 years	3 Participants n=39 Participants
Sex: Female, Male Female	8 Participants n=39 Participants
Sex: Female, Male Male	6 Participants n=39 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=39 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=39 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants
Race (NIH/OMB) Asian	0 Participants n=39 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants
Race (NIH/OMB) Black or African American	0 Participants n=39 Participants
Race (NIH/OMB) White	14 Participants n=39 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants

PRIMARY outcome

Timeframe: From date of study drug initiation until date of best response, assessed up to 6 years.

Outcome measures

Outcome measures
Measure	All Subjects n=14 Participants In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) Thalidomide: 50 mg oral dosing every other day Lenalidomide: varying oral doses every other day (max 25 mg/day) Rituximab: 375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Overall Response Rate as Defined as the Number of Patients Who Experience a Response (Complete or Partial) to Treatment at the Time of Best Response	12 Participants

SECONDARY outcome

Timeframe: From date of study drug initiation until date of progression or death, whichever occurs first, assessed through study completion up to 100 months.

Population: The one not assessable came off treatment prior to having an assessment.

Measured from time of study drug administration to progression or death, measured in months.

Outcome measures

Outcome measures
Measure	All Subjects n=13 Participants In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) Thalidomide: 50 mg oral dosing every other day Lenalidomide: varying oral doses every other day (max 25 mg/day) Rituximab: 375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Progression Free Survival	48 months Interval 22.0 to 54.0

SECONDARY outcome

Timeframe: From date of end of treatment to progression or death, whichever occurs first, assessed through study completion up to 100 months.

Population: The one not assessable came off treatment prior to having an assessment.

Measured from end of treatment to progression or death, measured in months.

Outcome measures

Outcome measures
Measure	All Subjects n=13 Participants In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) Thalidomide: 50 mg oral dosing every other day Lenalidomide: varying oral doses every other day (max 25 mg/day) Rituximab: 375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Duration of Response	70 months Interval 34.0 to 85.0

SECONDARY outcome

Timeframe: From date of study drug initiation to date of initial response, assessed up to 12 months.

Measured from time of study drug administration to initial response (partial or complete), measured in months.

Outcome measures

Outcome measures
Measure	All Subjects n=14 Participants In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) Thalidomide: 50 mg oral dosing every other day Lenalidomide: varying oral doses every other day (max 25 mg/day) Rituximab: 375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Time to Response	10 months Interval 3.0 to 12.0

SECONDARY outcome

Timeframe: From date of study drug initiation to date of death, assessed through study completion up to 105 months.

Measured from time of study drug administration to death, measured in months.

Outcome measures

Outcome measures
Measure	All Subjects n=14 Participants In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) Thalidomide: 50 mg oral dosing every other day Lenalidomide: varying oral doses every other day (max 25 mg/day) Rituximab: 375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Overall Survival	97 months Interval 13.0 to 105.0

Adverse Events

All Subjects

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Subjects n=14 participants at risk In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) Thalidomide: 50 mg oral dosing every other day Lenalidomide: varying oral doses every other day (max 25 mg/day) Rituximab: 375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Infections and infestations Pneumonia	7.1% 1/14 • Number of events 14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Renal and urinary disorders Acute renal insufficiency	7.1% 1/14 • Number of events 14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
General disorders Fever	7.1% 1/14 • Number of events 14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	7.1% 1/14 • Number of events 14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.

Other adverse events

Other adverse events
Measure	All Subjects n=14 participants at risk In Cycle -1, even numbered patients will receive oral lenalidomide daily on days 1-14 and then no treatment on days 15-28. In Cycle -1, odd numbered patients will receive oral thalidomide daily days 1-14 followed by no treatment on days 15-28. Starting with cycle 1, all patients will alternate daily thalidomide (every odd day) with daily lenalidomide (every even day) for days 1-28. Rituximab will be given on days 1, 8, 15, and 22 starting with Cycle 1, and then again every 6th cycle thereafter (cycles 7, 13, 19, etc.) Thalidomide: 50 mg oral dosing every other day Lenalidomide: varying oral doses every other day (max 25 mg/day) Rituximab: 375 mg/m2 intravenously on days 1, 8, 15, and 22 of cycle 1. Then, repeated on days 1, 8, 15, and 22 of every 6th cycle thereafter (Cycle 7, 13, 19, etc.)
Blood and lymphatic system disorders Anemia	42.9% 6/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Investigations Platelet count decreased	50.0% 7/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Blood and lymphatic system disorders Lymph node pain	35.7% 5/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Metabolism and nutrition disorders Hypocalcemia	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Gastrointestinal disorders Nausea	21.4% 3/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Investigations Blood bilirubin increased	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Investigations Lymphocyte count increased	21.4% 3/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Respiratory, thoracic and mediastinal disorders Sinus congestion	21.4% 3/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
General disorders Fever	28.6% 4/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Gastrointestinal disorders Constipation	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Gastrointestinal disorders Diarrhea	57.1% 8/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Investigations Lymphocyte count decreased	21.4% 3/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Skin and subcutaneous tissue disorders Rash	35.7% 5/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Metabolism and nutrition disorders Hypomagnesemia	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Musculoskeletal and connective tissue disorders Arthralgias	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Cardiac disorders Paroxysmal atrial fibrillation	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
General disorders Malaise	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Investigations Neutrophil count decreased	50.0% 7/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Investigations Creatinine increased	28.6% 4/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Infections and infestations Upper Respiratory infection	35.7% 5/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Investigations Aspartate aminotransferase increased	21.4% 3/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Nervous system disorders Headache	28.6% 4/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Investigations White blood cell decreased	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Metabolism and nutrition disorders Hypoalbuminemia	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Nervous system disorders Dizziness	21.4% 3/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Infections and infestations Sinusitis	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Gastrointestinal disorders Stomach pain	21.4% 3/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Metabolism and nutrition disorders Tumor lysis syndrome	7.1% 1/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Nervous system disorders Intermittent hemorhoidal hemorrhage	7.1% 1/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Nervous system disorders Neuropathy	42.9% 6/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Immune system disorders Allergic reaction	7.1% 1/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Musculoskeletal and connective tissue disorders Back pain	7.1% 1/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
General disorders Edema Face	7.1% 1/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
General disorders Localized edema	21.4% 3/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Musculoskeletal and connective tissue disorders Bone pain	7.1% 1/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	14.3% 2/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.
Cardiac disorders Aortic valve disease	7.1% 1/14 • From date of study drug initiation to 30 days post-date of last dose of study drug, assessed over an average of 3 years, 6 months.

Additional Information

Richard Furman, MD

Weill Cornell Medical College

Phone: 646-962-2064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place