Trial Outcomes & Findings for Ibrutinib, Nivolumab and Blinatumomab in Richter Transformation (NCT NCT03121534)
NCT ID: NCT03121534
Last Updated: 2023-02-17
Results Overview
Response is defined as complete remission (CR) plus partial remission (PR). Complete Remission (CR) is Lymph nodes None \>/= 1.5 cm, Spleen size \< 13 cm; normal liver size, the absence of constitutional symptoms, normal circulating lymphocyte count, platelets \>/= 100 x 10\^9/L, Hemoglobin \>/= 11.0 g/dL (absence of transfusion and without erythropoietin) and marrow normocellular, no CLL cells and no B-lymphoid nodules. Partial Remission (PR) is any two of the following must decrease \>/= 50% from baseline: lymph nodes, Liver and/or spleen size, circulating lymphocyte count in addition to one of the following: platelets \>/= 100 x 10\^9/L or \>/= 50% increase from baseline, Hemoglobin \>/= 11.0 g/dL or \>/= 50% increase from baseline or marrow presence of CLL cells, or of B-lymphoid nodules, or not done.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
9 participants
Primary outcome timeframe
2 months
Results posted on
2023-02-17
Participant Flow
Participant milestones
| Measure |
Ibrutinib, Nivolumab and Blinatumomab
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Ibrutinib, Nivolumab and Blinatumomab in Richter Transformation
Baseline characteristics by cohort
| Measure |
Ibrutinib, Nivolumab and Blinatumomab
n=9 Participants
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
|
Age, Continuous
|
66 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 monthsResponse is defined as complete remission (CR) plus partial remission (PR). Complete Remission (CR) is Lymph nodes None \>/= 1.5 cm, Spleen size \< 13 cm; normal liver size, the absence of constitutional symptoms, normal circulating lymphocyte count, platelets \>/= 100 x 10\^9/L, Hemoglobin \>/= 11.0 g/dL (absence of transfusion and without erythropoietin) and marrow normocellular, no CLL cells and no B-lymphoid nodules. Partial Remission (PR) is any two of the following must decrease \>/= 50% from baseline: lymph nodes, Liver and/or spleen size, circulating lymphocyte count in addition to one of the following: platelets \>/= 100 x 10\^9/L or \>/= 50% increase from baseline, Hemoglobin \>/= 11.0 g/dL or \>/= 50% increase from baseline or marrow presence of CLL cells, or of B-lymphoid nodules, or not done.
Outcome measures
| Measure |
Ibrutinib, Nivolumab and Blinatumomab
n=9 Participants
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
|
|---|---|
|
Number of Participants With a Response
|
2 Participants
|
SECONDARY outcome
Timeframe: Up to 4 years, 8 monthsComplete Remission is defined as: Complete Remission (CR) is Lymph nodes None \>/= 1.5 cm, Spleen size \< 13 cm; normal liver size, the absence of constitutional symptoms, normal circulating lymphocyte count, platelets \>/= 100 x 10\^9/L, Hemoglobin \>/= 11.0 g/dL (absence of transfusion and without erythropoietin) and marrow normocellular, no CLL cells and no B-lymphoid nodules.
Outcome measures
| Measure |
Ibrutinib, Nivolumab and Blinatumomab
n=9 Participants
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
|
|---|---|
|
Number of Participants to Achieve Complete Remission
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 4 years, 8 monthsTime from date of treatment start until the date of first objective documentation of disease-relapse.
Outcome measures
| Measure |
Ibrutinib, Nivolumab and Blinatumomab
n=2 Participants
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
|
|---|---|
|
Progression Free Survival
|
1.9 months
Interval 1.0 to 17.0
|
SECONDARY outcome
Timeframe: Up to 4 years, 8 MonthsTime from date of treatment start until date of death due to any cause or last Follow-up.
Outcome measures
| Measure |
Ibrutinib, Nivolumab and Blinatumomab
n=9 Participants
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
|
|---|---|
|
Overall Survival
|
10.3 Months
Interval 5.0 to 48.0
|
Adverse Events
Ibrutinib, Nivolumab and Blinatumomab
Serious events: 9 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ibrutinib, Nivolumab and Blinatumomab
n=9 participants at risk
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
|
|---|---|
|
Immune system disorders
Cytokine Release Syndrome
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
22.2%
2/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Injury, poisoning and procedural complications
Fracture
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Nervous system disorders
Nervous System Disorder
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Investigations
Creatinine Increased
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Infections and infestations
Lung Infection
|
33.3%
3/9 • Number of events 3 • Up to 4 years, 8 months
|
|
General disorders
Chills
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
General disorders
Fatigue
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Vascular disorders
Hypotension
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
General disorders
Fever
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
Other adverse events
| Measure |
Ibrutinib, Nivolumab and Blinatumomab
n=9 participants at risk
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
|
|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Investigations
Alanine aminotransferase increased
|
22.2%
2/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Investigations
Alkaline phosphatase increased
|
33.3%
3/9 • Number of events 3 • Up to 4 years, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Gastrointestinal disorders
Anorexia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Investigations
Aspartate aminotransferase increased
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Cardiac disorders
Atrial fibrillation
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Investigations
Blood bilirubin increased
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Skin and subcutaneous tissue disorders
Bruising
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
General disorders
Chills
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Psychiatric disorders
Confusion
|
22.2%
2/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Investigations
Creatinine increased
|
22.2%
2/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Immune system disorders
Cytokine release syndrome
|
22.2%
2/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Nervous system disorders
Dysgeusia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Nervous system disorders
Dysphasia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
General disorders
Edema
|
22.2%
2/9 • Number of events 3 • Up to 4 years, 8 months
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Injury, poisoning and procedural complications
Fall
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
General disorders
Fatigue
|
44.4%
4/9 • Number of events 5 • Up to 4 years, 8 months
|
|
General disorders
Fever
|
55.6%
5/9 • Number of events 6 • Up to 4 years, 8 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
General disorders
General disorders and administration site conditions
|
22.2%
2/9 • Number of events 3 • Up to 4 years, 8 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Ear and labyrinth disorders
Hearing impaired
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
33.3%
3/9 • Number of events 3 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Vascular disorders
Hypertension
|
22.2%
2/9 • Number of events 3 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
22.2%
2/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
22.2%
2/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
22.2%
2/9 • Number of events 3 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Vascular disorders
Hypotension
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Investigations
Investigations
|
33.3%
3/9 • Number of events 12 • Up to 4 years, 8 months
|
|
Infections and infestations
Lung infection
|
33.3%
3/9 • Number of events 4 • Up to 4 years, 8 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Nervous system disorders
Nervous system disorders
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Gastrointestinal disorders
Oral dysesthesia
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Nervous system disorders
Paresthesia
|
11.1%
1/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Gastrointestinal disorders
cough
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
General disorders
Pain
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Cardiac disorders
Sinus tachycardia
|
22.2%
2/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
11.1%
1/9 • Number of events 2 • Up to 4 years, 8 months
|
|
Reproductive system and breast disorders
Testicular disorder
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Nervous system disorders
Tremor
|
33.3%
3/9 • Number of events 3 • Up to 4 years, 8 months
|
|
Investigations
Weight gain
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
|
Investigations
Weight loss
|
11.1%
1/9 • Number of events 1 • Up to 4 years, 8 months
|
Additional Information
Philip Thompson MD.
The University of Texas MD Anderson Cancer Center
Phone: 713-745-5732
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place