Trial Outcomes & Findings for Fludarabine, Rituximab, and Lenalidomide in Minimally Treated/Untreated Patients With Chronic Lymphocytic Leukemia (CLL) (NCT NCT00536341)
NCT ID: NCT00536341
Last Updated: 2017-01-16
Results Overview
Recorded from first treatment until 30 days after last treatment and assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
64 participants
Primary outcome timeframe
63 months
Results posted on
2017-01-16
Participant Flow
Participant milestones
| Measure |
Dose Level 1
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 all cycles 1-6
|
Dose Level 2
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 cycle 1, 5.0 mg PO days 8-28 cycles 2-6
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
54
|
|
Overall Study
COMPLETED
|
5
|
43
|
|
Overall Study
NOT COMPLETED
|
5
|
11
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Fludarabine, Rituximab, and Lenalidomide in Minimally Treated/Untreated Patients With Chronic Lymphocytic Leukemia (CLL)
Baseline characteristics by cohort
| Measure |
Dose Level 1
n=10 Participants
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 all cycles 1-6
|
Dose Level 2
n=54 Participants
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 cycle 1, 5.0 mg PO days 8-28 cycles 2-6
|
Total
n=64 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67 years
n=5 Participants
|
63 years
n=7 Participants
|
64 years
n=5 Participants
|
|
Gender
Female
|
2 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Gender
Male
|
8 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
54 participants
n=7 Participants
|
64 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 63 monthsPopulation: All treated patients
Recorded from first treatment until 30 days after last treatment and assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Outcome measures
| Measure |
Dose Level 1
n=10 Participants
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 all cycles 1-6
|
Dose Level 2
n=54 Participants
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 cycle 1, 5.0 mg PO days 8-28 cycles 2-6
|
|---|---|---|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Fatigue
|
8 participants
|
40 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Neutropenia
|
7 participants
|
41 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Anemia
|
8 participants
|
34 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Leukopenia
|
7 participants
|
34 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Thrombocytopenia
|
8 participants
|
30 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Rash
|
6 participants
|
27 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Nausea
|
7 participants
|
25 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Constipation
|
3 participants
|
15 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Anorexia
|
4 participants
|
12 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Fever
|
3 participants
|
13 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Hyperhidrosis
|
3 participants
|
13 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Arthralgia
|
1 participants
|
14 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Edema Limbs
|
3 participants
|
12 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Pruritus
|
0 participants
|
15 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Back pain
|
3 participants
|
11 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Headache
|
1 participants
|
13 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Chills
|
2 participants
|
11 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Insomnia
|
2 participants
|
11 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Vomiting
|
2 participants
|
11 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Dysgeusia
|
1 participants
|
11 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Abdominal Pain
|
2 participants
|
9 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Allergic Reaction
|
4 participants
|
7 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Diarrhea
|
3 participants
|
8 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Cough
|
2 participants
|
8 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Dizziness
|
2 participants
|
8 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Dyspnea
|
0 participants
|
10 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Hypotension
|
1 participants
|
9 participants
|
|
Number of Adverse Events as a Measure of Safety and Tolerability
Myalgia
|
2 participants
|
8 participants
|
PRIMARY outcome
Timeframe: At 12 weeks during treatment and 2 months post-treatment until disease progression, projected 8 monthsPopulation: All patients deemed evaluable and evaluated for response
An improvement in complete response to at least 60% following treatment, assessed using CT scans, clinical/lab examinations, and bone marrow aspirations, as defined by National Cancer Institute Working Group Response Criteria.
Outcome measures
| Measure |
Dose Level 1
n=9 Participants
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 all cycles 1-6
|
Dose Level 2
n=41 Participants
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 cycle 1, 5.0 mg PO days 8-28 cycles 2-6
|
|---|---|---|
|
Complete Response Rate
|
4 participants
|
9 participants
|
SECONDARY outcome
Timeframe: Every 3 months during treatment until disease progression and every 6 months thereafter, up to 5 yearsPopulation: All treated patients, all dose levels
Measured from first treatment to disease progression and assessed using Kaplan-Meier methods.
Outcome measures
| Measure |
Dose Level 1
n=64 Participants
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 all cycles 1-6
|
Dose Level 2
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 cycle 1, 5.0 mg PO days 8-28 cycles 2-6
|
|---|---|---|
|
Progression-Free Survival
|
24.64 months
Interval 21.125 to
Not reached at this time
|
—
|
SECONDARY outcome
Timeframe: Every 3 months until treatment discontinuation, expected average of 6 months and then every 6 months thereafter up to 5 yearsPopulation: All treated patients, all dose levels
Defined as the time from Day 1 of treatment administration to date of death from any cause, estimated using Kaplan-Meier methods.
Outcome measures
| Measure |
Dose Level 1
n=64 Participants
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 all cycles 1-6
|
Dose Level 2
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 cycle 1, 5.0 mg PO days 8-28 cycles 2-6
|
|---|---|---|
|
Overall Survival
|
NA months
Median OS not reached at this time
|
—
|
Adverse Events
Dose Level 1
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
Dose Level 2
Serious events: 16 serious events
Other events: 54 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dose Level 1
n=10 participants at risk
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 all cycles 1-6
|
Dose Level 2
n=54 participants at risk
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 cycle 1, 5.0 mg PO days 8-28 cycles 2-6
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
1/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Immune system disorders
Allergic Reaction
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Infections and infestations
Bronchial Infection
|
0.00%
0/10 • 63 months
|
3.7%
2/54 • 63 months
|
|
General disorders
Chills
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
General disorders
Edema limbs
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
General disorders
Fatigue
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
General disorders
Fever
|
0.00%
0/10 • 63 months
|
3.7%
2/54 • 63 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Infections and infestations
Infections and infestations - Other, gastrointestinal infection NOS
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Infections and infestations
Infections and infestations - Other, pneumonia
|
10.0%
1/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Infections and infestations
Infections and infestations - Other, unspecified
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Gastrointestinal disorders
Mucositis
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/10 • 63 months
|
3.7%
2/54 • 63 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Metabolism and nutrition disorders
Tumor Lysis Syndrome
|
0.00%
0/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Investigations
White blood cell decreased
|
0.00%
0/10 • 63 months
|
3.7%
2/54 • 63 months
|
Other adverse events
| Measure |
Dose Level 1
n=10 participants at risk
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 all cycles 1-6
|
Dose Level 2
n=54 participants at risk
Rituximab 375 mg/m\^2 cycle 1 (split over Day 1 \& Day 2), 500 mg/m\^2 Day 1 of cycles 2-6 Fludarabine 25 mg/m\^2 on days 1, 2 and 3 Lenalidomide 2.5 mg PO daily Days 8-28 cycle 1, 5.0 mg PO days 8-28 cycles 2-6
|
|---|---|---|
|
General disorders
Fatigue
|
80.0%
8/10 • 63 months
|
74.1%
40/54 • 63 months
|
|
Investigations
Neutrophil count decreased
|
70.0%
7/10 • 63 months
|
75.9%
41/54 • 63 months
|
|
Blood and lymphatic system disorders
Anemia
|
80.0%
8/10 • 63 months
|
63.0%
34/54 • 63 months
|
|
Investigations
White blood cell decreased
|
70.0%
7/10 • 63 months
|
63.0%
34/54 • 63 months
|
|
Investigations
Platelet count decreased
|
80.0%
8/10 • 63 months
|
55.6%
30/54 • 63 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
60.0%
6/10 • 63 months
|
50.0%
27/54 • 63 months
|
|
Gastrointestinal disorders
Nausea
|
70.0%
7/10 • 63 months
|
46.3%
25/54 • 63 months
|
|
Gastrointestinal disorders
Constipation
|
30.0%
3/10 • 63 months
|
27.8%
15/54 • 63 months
|
|
Metabolism and nutrition disorders
Anorexia
|
40.0%
4/10 • 63 months
|
22.2%
12/54 • 63 months
|
|
General disorders
Fever
|
30.0%
3/10 • 63 months
|
24.1%
13/54 • 63 months
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
30.0%
3/10 • 63 months
|
24.1%
13/54 • 63 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
1/10 • 63 months
|
25.9%
14/54 • 63 months
|
|
General disorders
Edema limbs
|
30.0%
3/10 • 63 months
|
22.2%
12/54 • 63 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/10 • 63 months
|
27.8%
15/54 • 63 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
30.0%
3/10 • 63 months
|
20.4%
11/54 • 63 months
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • 63 months
|
24.1%
13/54 • 63 months
|
|
General disorders
Chills
|
20.0%
2/10 • 63 months
|
20.4%
11/54 • 63 months
|
|
Psychiatric disorders
Insomnia
|
20.0%
2/10 • 63 months
|
20.4%
11/54 • 63 months
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
2/10 • 63 months
|
20.4%
11/54 • 63 months
|
|
Nervous system disorders
dysgeusia
|
10.0%
1/10 • 63 months
|
20.4%
11/54 • 63 months
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
2/10 • 63 months
|
16.7%
9/54 • 63 months
|
|
Immune system disorders
Allergic reaction
|
40.0%
4/10 • 63 months
|
13.0%
7/54 • 63 months
|
|
Gastrointestinal disorders
Diarrhea
|
30.0%
3/10 • 63 months
|
14.8%
8/54 • 63 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
2/10 • 63 months
|
14.8%
8/54 • 63 months
|
|
Nervous system disorders
Dizziness
|
20.0%
2/10 • 63 months
|
14.8%
8/54 • 63 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/10 • 63 months
|
18.5%
10/54 • 63 months
|
|
Vascular disorders
Hypotension
|
10.0%
1/10 • 63 months
|
16.7%
9/54 • 63 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
20.0%
2/10 • 63 months
|
14.8%
8/54 • 63 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
20.0%
2/10 • 63 months
|
13.0%
7/54 • 63 months
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/10 • 63 months
|
14.8%
8/54 • 63 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
10.0%
1/10 • 63 months
|
13.0%
7/54 • 63 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
20.0%
2/10 • 63 months
|
11.1%
6/54 • 63 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.0%
1/10 • 63 months
|
13.0%
7/54 • 63 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
30.0%
3/10 • 63 months
|
7.4%
4/54 • 63 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/10 • 63 months
|
13.0%
7/54 • 63 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
10.0%
1/10 • 63 months
|
11.1%
6/54 • 63 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/10 • 63 months
|
13.0%
7/54 • 63 months
|
|
Investigations
Alanine aminotransferase increased
|
10.0%
1/10 • 63 months
|
9.3%
5/54 • 63 months
|
|
Investigations
Alkaline phosphatase increased
|
10.0%
1/10 • 63 months
|
9.3%
5/54 • 63 months
|
|
Gastrointestinal disorders
Mucositis
|
0.00%
0/10 • 63 months
|
11.1%
6/54 • 63 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/10 • 63 months
|
9.3%
5/54 • 63 months
|
|
Psychiatric disorders
depression
|
0.00%
0/10 • 63 months
|
9.3%
5/54 • 63 months
|
|
Infections and infestations
Infections and infestations - Other, unspecified
|
10.0%
1/10 • 63 months
|
7.4%
4/54 • 63 months
|
|
Investigations
Investigations - Other, LDH increased
|
0.00%
0/10 • 63 months
|
9.3%
5/54 • 63 months
|
|
Nervous system disorders
Tremor
|
10.0%
1/10 • 63 months
|
7.4%
4/54 • 63 months
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/10 • 63 months
|
7.4%
4/54 • 63 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/10 • 63 months
|
7.4%
4/54 • 63 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/10 • 63 months
|
7.4%
4/54 • 63 months
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
10.0%
1/10 • 63 months
|
5.6%
3/54 • 63 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/10 • 63 months
|
7.4%
4/54 • 63 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
10.0%
1/10 • 63 months
|
5.6%
3/54 • 63 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, erythema
|
30.0%
3/10 • 63 months
|
1.9%
1/54 • 63 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
20.0%
2/10 • 63 months
|
3.7%
2/54 • 63 months
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/10 • 63 months
|
7.4%
4/54 • 63 months
|
Additional Information
John D Hainsworth, MD
Sarah Cannon Research Institute
Phone: 1-877-691-7274
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 but =180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
- Publication restrictions are in place
Restriction type: OTHER