Trial Outcomes & Findings for Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory CLL and SLL (NCT NCT01173679)
NCT ID: NCT01173679
Last Updated: 2017-04-14
Results Overview
To describe the response rate of complete response (CR) and partial response (PR) to treatment with this drug combination (SD=stable disease, PD=progressive disease)
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
2 years
Results posted on
2017-04-14
Participant Flow
Participant milestones
| Measure |
Dasatinib, Rituximab, Fludarabine
Single-arm
dasatinib: Taken orally once a day on days 1-14 of each 28-day cycle
Rituximab: Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).
fludarabine: Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
|
|---|---|
|
Overall Study
STARTED
|
10
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Dasatinib, Rituximab, Fludarabine
Single-arm
dasatinib: Taken orally once a day on days 1-14 of each 28-day cycle
Rituximab: Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).
fludarabine: Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
|
|---|---|
|
Overall Study
Death
|
1
|
Baseline Characteristics
Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory CLL and SLL
Baseline characteristics by cohort
| Measure |
Dasatinib, Rituximab, Fludarabine
n=10 Participants
Single-arm
dasatinib: Taken orally once a day on days 1-14 of each 28-day cycle
Rituximab: Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).
fludarabine: Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
|
|---|---|
|
Age, Continuous
|
68 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
10 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 2 yearsTo describe the response rate of complete response (CR) and partial response (PR) to treatment with this drug combination (SD=stable disease, PD=progressive disease)
Outcome measures
| Measure |
Dasatinib, Rituximab, Fludarabine
n=10 Participants
Single-arm, open-label
dasatinib: Taken orally once a day on days 1-14 of each 28-day cycle
Rituximab: Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).
fludarabine: Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
|
|---|---|
|
Response Rate
CR
|
2 Participants
|
|
Response Rate
PR
|
2 Participants
|
|
Response Rate
SD
|
5 Participants
|
|
Response Rate
PD
|
1 Participants
|
SECONDARY outcome
Timeframe: 2 yearsTo describe the progression-free and overall surivial
Outcome measures
| Measure |
Dasatinib, Rituximab, Fludarabine
n=10 Participants
Single-arm, open-label
dasatinib: Taken orally once a day on days 1-14 of each 28-day cycle
Rituximab: Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).
fludarabine: Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
|
|---|---|
|
Progression-Free and Overall Survival
Progression-free survival
|
8.75 months
Interval 2.75 to 13.0
|
|
Progression-Free and Overall Survival
Overall survival
|
24 months
Interval 16.25 to 24.0
|
SECONDARY outcome
Timeframe: 2 yearsDasatinib may enhance the myelosuppression expected from fludarabine. This toxicity will be monitored with frequent CBC's. If after Day 21 of a cycle there is a grade 4 cytopenia, a dose reduction will occur in the next cycle of treatment, and that cycle cannot start until the ANC \> 1,000 and the platelets \> 25,000. There is also a risk for pleural effusions with dasatinib, but the risk will be low, since there is a break from dasatinib dosing on days 15-28 of each cycle. Nevertheless, if a grade 2 pleural effusion occurs, there will be a dose reduction in the next cycle of treatment.
Outcome measures
| Measure |
Dasatinib, Rituximab, Fludarabine
n=10 Participants
Single-arm, open-label
dasatinib: Taken orally once a day on days 1-14 of each 28-day cycle
Rituximab: Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).
fludarabine: Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
|
|---|---|
|
Toxicities
Pleural effusion · 5
|
0 Participants
|
|
Toxicities
Platelets · 3
|
4 Participants
|
|
Toxicities
Platelets · 4
|
3 Participants
|
|
Toxicities
Platelets · 5
|
0 Participants
|
|
Toxicities
Platelets · Did not have any
|
3 Participants
|
|
Toxicities
Neutropenia · 3
|
3 Participants
|
|
Toxicities
Neutropenia · 4
|
3 Participants
|
|
Toxicities
Neutropenia · 5
|
0 Participants
|
|
Toxicities
Neutropenia · Did not have any
|
4 Participants
|
|
Toxicities
Fatigue · 3
|
1 Participants
|
|
Toxicities
Fatigue · 4
|
0 Participants
|
|
Toxicities
Fatigue · 5
|
0 Participants
|
|
Toxicities
Fatigue · Did not have any
|
9 Participants
|
|
Toxicities
Dyspnea · 3
|
1 Participants
|
|
Toxicities
Dyspnea · 4
|
0 Participants
|
|
Toxicities
Dyspnea · 5
|
0 Participants
|
|
Toxicities
Dyspnea · Did not have any
|
9 Participants
|
|
Toxicities
Pleural effusion · 3
|
1 Participants
|
|
Toxicities
Pleural effusion · 4
|
0 Participants
|
|
Toxicities
Pleural effusion · Did not have any
|
9 Participants
|
|
Toxicities
Bleeding · 3
|
1 Participants
|
|
Toxicities
Bleeding · 4
|
0 Participants
|
|
Toxicities
Bleeding · 5
|
0 Participants
|
|
Toxicities
Bleeding · Did not have any
|
9 Participants
|
|
Toxicities
Fever alone · 3
|
1 Participants
|
|
Toxicities
Fever alone · 4
|
0 Participants
|
|
Toxicities
Fever alone · 5
|
0 Participants
|
|
Toxicities
Fever alone · Did not have any
|
9 Participants
|
|
Toxicities
Infection · 3
|
0 Participants
|
|
Toxicities
Infection · 4
|
0 Participants
|
|
Toxicities
Infection · 5
|
1 Participants
|
|
Toxicities
Infection · Did not have any
|
9 Participants
|
Adverse Events
Dasatinib, Rituximab, Fludarabine
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dasatinib, Rituximab, Fludarabine
n=10 participants at risk
Single-arm
dasatinib: Taken orally once a day on days 1-14 of each 28-day cycle
Rituximab: Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).
fludarabine: Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
10.0%
1/10 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
10.0%
1/10 • Number of events 1
|
Other adverse events
| Measure |
Dasatinib, Rituximab, Fludarabine
n=10 participants at risk
Single-arm
dasatinib: Taken orally once a day on days 1-14 of each 28-day cycle
Rituximab: Given intravenously, 375 mg/m2 each cycle (dose split, given on Days 3+4 of cycle 1, variable after that).
fludarabine: Given intravenously, 25 mg/m2/day, for 3 doses per cycle (Days 3-5 in cycle 1, Days 1-3 after that)
|
|---|---|
|
General disorders
Fatigue
|
50.0%
5/10 • Number of events 18
|
|
Blood and lymphatic system disorders
Anemia
|
50.0%
5/10 • Number of events 14
|
|
Investigations
Platelet count decreased
|
50.0%
5/10 • Number of events 14
|
|
Gastrointestinal disorders
Nausea
|
50.0%
5/10 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
40.0%
4/10 • Number of events 12
|
|
Investigations
White blood cell decreased
|
40.0%
4/10 • Number of events 11
|
|
Investigations
Blood bilirubin increased
|
40.0%
4/10 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
40.0%
4/10 • Number of events 9
|
|
General disorders
Chills
|
40.0%
4/10 • Number of events 8
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
40.0%
4/10 • Number of events 8
|
|
Investigations
Neutrophil count decreased
|
40.0%
4/10 • Number of events 5
|
|
Gastrointestinal disorders
Diarrhea
|
40.0%
4/10 • Number of events 4
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
30.0%
3/10 • Number of events 4
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
30.0%
3/10 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal pain
|
30.0%
3/10 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
30.0%
3/10 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
20.0%
2/10 • Number of events 5
|
|
Investigations
Alkaline phosphatase increased
|
20.0%
2/10 • Number of events 4
|
|
Investigations
Aspartate aminotransferase increased
|
20.0%
2/10 • Number of events 4
|
|
General disorders
Edema limbs
|
20.0%
2/10 • Number of events 3
|
|
Infections and infestations
Mucosal infection
|
20.0%
2/10 • Number of events 3
|
|
Investigations
Lymphocyte count increased
|
20.0%
2/10 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
20.0%
2/10 • Number of events 3
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
20.0%
2/10 • Number of events 2
|
|
General disorders
Fever
|
20.0%
2/10 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
20.0%
2/10 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
2/10 • Number of events 2
|
|
Infections and infestations
Upper respiratory infection
|
20.0%
2/10 • Number of events 2
|
|
Infections and infestations
Infections and infestations - Other, specify
|
20.0%
2/10 • Number of events 2
|
|
Investigations
Lymphocyte count decreased
|
20.0%
2/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Dehydration
|
20.0%
2/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
20.0%
2/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
20.0%
2/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatremia
|
20.0%
2/10 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
20.0%
2/10 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness right-sided
|
20.0%
2/10 • Number of events 2
|
|
Blood and lymphatic system disorders
Leukocytosis
|
10.0%
1/10 • Number of events 2
|
|
Investigations
Alanine aminotransferase increased
|
10.0%
1/10 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial stricture
|
10.0%
1/10 • Number of events 2
|
|
Cardiac disorders
Heart failure
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Infusion related reaction
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Pain
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
10.0%
1/10 • Number of events 1
|
|
Endocrine disorders
Hyperthyroidism
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Ascites
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Ileal perforation
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
10.0%
1/10 • Number of events 1
|
|
Immune system disorders
Allergic reaction
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Gum infection
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Skin infection
|
10.0%
1/10 • Number of events 1
|
|
Injury, poisoning and procedural complications
Bruising
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Creatinine increased
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Anorexia
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypernatremia
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalemia
|
10.0%
1/10 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
1/10 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
10.0%
1/10 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Acoustic nerve disorder NOS
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Brachial plexopathy
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Movements involuntary
|
10.0%
1/10 • Number of events 1
|
|
Eye disorders
Conjunctivitis
|
10.0%
1/10 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
10.0%
1/10 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
10.0%
1/10 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Laryngopharyngeal dysesthesia
|
10.0%
1/10 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
10.0%
1/10 • Number of events 1
|
|
Renal and urinary disorders
Acute kidney injury
|
10.0%
1/10 • Number of events 1
|
|
Vascular disorders
Hypertension
|
10.0%
1/10 • Number of events 1
|
|
Blood and lymphatic system disorders
Platelets
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Taste disturbance
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Back- pain
|
10.0%
1/10 • Number of events 1
|
|
General disorders
|
80.0%
8/10 • Number of events 10
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place