Trial Outcomes & Findings for Nivolumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or High-Risk Untreated Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Richter Transformation (NCT NCT02420912)
NCT ID: NCT02420912
Last Updated: 2024-03-20
Results Overview
Response is Complete Response (CR) + Partial Response (PR). CR = Peripheral blood Lymphocytes \<4000/uL, no lymphadenopathy, no hepatomegaly or splenomegaly by exam or scan, absence of symptoms, neutrophils \> 1,500/uL, Platelets \> 1000,000/uL, hemoglobin \> 11.0 g/dl (untransfused) and normocellular bone marrow \< 30% nucleated cells being lymphocytes, no lymphoid nodules. PR = 1 for \>/= 2 months: \>/= 50% decrease in peripheral lymphocyte count from baseline, \>/= 50% reduction in lymphadenopathy, \>/= 50% reduction in pretreatment enlargement of the spleen or liver by scan. Additionally for PR must have 1 of the following for \>/= 2 months: Neutrophils \> 1,500/uL, Platelets \> 100,000/uL or \>/= 50% improvement over baseline or Hemoglobin \> 11.0 g/dl (untransfused) or \>/= 50% improvement over baseline. Additionally if patients fufill CR but have one of the following, be considered a PR: bone marrow nodules or persistent anemia, thrombocytopenia, neutropenia unrelated to disease.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
37 participants
Primary outcome timeframe
Up to 12 months
Results posted on
2024-03-20
Participant Flow
Participant milestones
| Measure |
Cohort I (Nivolumab, Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
Patients receive nivolumab IV over 1 hour on days 1 and 15 and ibrutinib PO QD on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort II (Nivolumab, Previous Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort III (Nivolumab, Ibrutinib) Richters Transformation (RT)
Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
|---|---|---|---|
|
Overall Study
STARTED
|
7
|
3
|
26
|
|
Overall Study
COMPLETED
|
7
|
3
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nivolumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or High-Risk Untreated Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Richter Transformation
Baseline characteristics by cohort
| Measure |
Cohort I (Nivolumab, Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=7 Participants
Patients receive nivolumab IV over 1 hour on days 1 and 15 and ibrutinib PO QD on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort II (Nivolumab, Previous Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=3 Participants
Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort III (Nivolumab, Ibrutinib) Richters Transformation (RT)
n=26 Participants
Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Age, Continuous
|
57 years
n=5 Participants
|
64 years
n=7 Participants
|
65 years
n=5 Participants
|
64 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
3 participants
n=7 Participants
|
26 participants
n=5 Participants
|
36 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: This outcome measure was only designed for those participants in cohort 1 and 3.
Response is Complete Response (CR) + Partial Response (PR). CR = Peripheral blood Lymphocytes \<4000/uL, no lymphadenopathy, no hepatomegaly or splenomegaly by exam or scan, absence of symptoms, neutrophils \> 1,500/uL, Platelets \> 1000,000/uL, hemoglobin \> 11.0 g/dl (untransfused) and normocellular bone marrow \< 30% nucleated cells being lymphocytes, no lymphoid nodules. PR = 1 for \>/= 2 months: \>/= 50% decrease in peripheral lymphocyte count from baseline, \>/= 50% reduction in lymphadenopathy, \>/= 50% reduction in pretreatment enlargement of the spleen or liver by scan. Additionally for PR must have 1 of the following for \>/= 2 months: Neutrophils \> 1,500/uL, Platelets \> 100,000/uL or \>/= 50% improvement over baseline or Hemoglobin \> 11.0 g/dl (untransfused) or \>/= 50% improvement over baseline. Additionally if patients fufill CR but have one of the following, be considered a PR: bone marrow nodules or persistent anemia, thrombocytopenia, neutropenia unrelated to disease.
Outcome measures
| Measure |
Cohort I (Nivolumab, Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=7 Participants
Patients receive nivolumab IV over 1 hour on days 1 and 15 and ibrutinib PO QD on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort II (Nivolumab, Previous Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort III (Nivolumab, Ibrutinib) Richters Transformation (RT)
n=26 Participants
Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
|---|---|---|---|
|
Number of Participants With a Response for Cohorts 1 and 3
|
5 Participants
|
—
|
10 Participants
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: This outcome measure was designed for participants from Cohort 2, already on ibrutinib treatment.
Complete Response (CR) = Peripheral blood Lymphocytes \<4000/uL, no lymphadenopathy, no hepatomegaly or splenomegaly by exam or scan, absence of symptoms, neutrophils \> 1,500/uL, Platelets \> 1000,000/uL, hemoglobin \> 11.0 g/dl (untransfused) and normocellular bone marrow \< 30% nucleated cells being lymphocytes, no lymphoid nodules. Partial Response (PR) = 1 for \>/= 2 months: \>/= 50% decrease in peripheral lymphocyte count from baseline, \>/= 50% reduction in lymphadenopathy, \>/= 50% reduction in pretreatment enlargement of the spleen or liver by scan. Additionally for PR must have 1 of the following for \>/= 2 months: Neutrophils \> 1,500/uL, Platelets \> 100,000/uL or \>/= 50% improvement over baseline or Hemoglobin \> 11.0 g/dl (untransfused) or \>/= 50% improvement over baseline. Additionally if patients fufill CR but have one of the following, be considered a PR: bone marrow nodules or persistent anemia, thrombocytopenia, neutropenia unrelated to disease.
Outcome measures
| Measure |
Cohort I (Nivolumab, Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
Patients receive nivolumab IV over 1 hour on days 1 and 15 and ibrutinib PO QD on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort II (Nivolumab, Previous Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=3 Participants
Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort III (Nivolumab, Ibrutinib) Richters Transformation (RT)
Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
|---|---|---|---|
|
Number of Participants in Cohort 2 to Convert From a Partial Response (PR) to Complete Response (CR)
|
—
|
1 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to 6 years, 7 monthsPopulation: Two participants in Cohort 3 were not evaluable for response.
Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be presented by median survival, which is the time point at which the cumulative survival drops below 50%. If there is no median survival (not reached), it means the cumulative survival was more than 50%.
Outcome measures
| Measure |
Cohort I (Nivolumab, Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=7 Participants
Patients receive nivolumab IV over 1 hour on days 1 and 15 and ibrutinib PO QD on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort II (Nivolumab, Previous Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=3 Participants
Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort III (Nivolumab, Ibrutinib) Richters Transformation (RT)
n=24 Participants
Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
|---|---|---|---|
|
Overall Survival (OS)
|
NA months
Interval 8.2 to 79.0
The median overall survival for Cohort 1 was Not Reached. insufficient number of participants with events
|
NA months
Interval 78.0 to 79.0
The median overall survival for Cohort 2 was Not Reached. insufficient number of participants with events and zero patients died while they were onstudy.
|
NA months
Interval 1.0 to 19.0
The median overall survival for Cohort 3 was Not Reached. insufficient number of participants with events
|
SECONDARY outcome
Timeframe: Up to 6 years, 7 monthsPopulation: Two participants in Cohort 3 were not evaluable for response.
Time from date of treatment start until the date of first objective documentation of disease-relapse.
Outcome measures
| Measure |
Cohort I (Nivolumab, Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=7 Participants
Patients receive nivolumab IV over 1 hour on days 1 and 15 and ibrutinib PO QD on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort II (Nivolumab, Previous Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=3 Participants
Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort III (Nivolumab, Ibrutinib) Richters Transformation (RT)
n=24 Participants
Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
|---|---|---|---|
|
Progression-free Survival (PFS)
|
50.1 Months
Interval 4.6 to 79.0
|
22.3 Months
Interval 7.8 to 46.7
|
15 Months
Interval 3.5 to 17.5
|
Adverse Events
Cohort I (Nivolumab, Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
Serious events: 3 serious events
Other events: 7 other events
Deaths: 3 deaths
Cohort II (Nivolumab, Previous Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort III (Nivolumab, Ibrutinib) Richters Transformation (RT)
Serious events: 15 serious events
Other events: 19 other events
Deaths: 13 deaths
Serious adverse events
| Measure |
Cohort I (Nivolumab, Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=7 participants at risk
Patients receive nivolumab IV over 1 hour on days 1 and 15 and ibrutinib PO QD on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort II (Nivolumab, Previous Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=3 participants at risk
Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort III (Nivolumab, Ibrutinib) Richters Transformation (RT)
n=26 participants at risk
Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
|---|---|---|---|
|
General disorders
Abdominal pain
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Cardiac disorders
Atrial fibrillation
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 2 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Dehydration
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Diarrhea
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
14.3%
1/7 • Number of events 4 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
General disorders
Fever
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 4 • Up to 6 years, 7 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Infections and infestations
Lung infection
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
19.2%
5/26 • Number of events 8 • Up to 6 years, 7 months
|
|
Blood and lymphatic system disorders
Lymph node pain
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/7 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 3 • Up to 6 years, 7 months
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Metabolism and nutrition disorders
Tumor lysis syndrome
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Infections and infestations
Urinary tract infection
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 2 • Up to 6 years, 7 months
|
Other adverse events
| Measure |
Cohort I (Nivolumab, Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=7 participants at risk
Patients receive nivolumab IV over 1 hour on days 1 and 15 and ibrutinib PO QD on days 1-28 of courses 2-24. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort II (Nivolumab, Previous Ibrutinib) Chronic Lymphocytic Leukemia (CLL)
n=3 participants at risk
Patients receive nivolumab as in Cohort I and continue previous ibrutinib treatment.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
Cohort III (Nivolumab, Ibrutinib) Richters Transformation (RT)
n=26 participants at risk
Patients receive nivolumab and ibrutinib as in cohort I. Ibrutinib may be given earlier than course 2 in case of worsening disease after discussion with study principal investigator. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
|
|---|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Ear and labyrinth disorders
Acute Otitis Media
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 2 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Anorexia
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Psychiatric disorders
Anxiety
|
28.6%
2/7 • Number of events 2 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
71.4%
5/7 • Number of events 7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
23.1%
6/26 • Number of events 6 • Up to 6 years, 7 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
28.6%
2/7 • Number of events 3 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Cardiac disorders
Atrial fibrillation
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Eye disorders
Blurred vision
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Injury, poisoning and procedural complications
Bruising
|
57.1%
4/7 • Number of events 6 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
23.1%
6/26 • Number of events 7 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
11.5%
3/26 • Number of events 3 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
11.5%
3/26 • Number of events 4 • Up to 6 years, 7 months
|
|
General disorders
Decreased Hearing
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Dental caries
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Diarrhea
|
42.9%
3/7 • Number of events 4 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
19.2%
5/26 • Number of events 6 • Up to 6 years, 7 months
|
|
Nervous system disorders
Dizziness
|
42.9%
3/7 • Number of events 3 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Dry Mouth
|
14.3%
1/7 • Number of events 2 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Nervous system disorders
Dysphasia
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
28.6%
2/7 • Number of events 2 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Injury, poisoning and procedural complications
Fall
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 2 • Up to 6 years, 7 months
|
|
General disorders
Fatigue
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
66.7%
2/3 • Number of events 2 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 2 • Up to 6 years, 7 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
14.3%
1/7 • Number of events 4 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 2 • Up to 6 years, 7 months
|
|
General disorders
Fever
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
11.5%
3/26 • Number of events 7 • Up to 6 years, 7 months
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/7 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 2 • Up to 6 years, 7 months
|
|
Nervous system disorders
Headache
|
28.6%
2/7 • Number of events 2 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Vascular disorders
Hypertension
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Psychiatric disorders
Insomnia
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Infections and infestations
Lung infection
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
19.2%
5/26 • Number of events 6 • Up to 6 years, 7 months
|
|
General disorders
Malaise
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
14.3%
1/7 • Number of events 2 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 2 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Nausea
|
42.9%
3/7 • Number of events 3 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
15.4%
4/26 • Number of events 4 • Up to 6 years, 7 months
|
|
Nervous system disorders
Nervous system disorders
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
66.7%
2/3 • Number of events 2 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
General disorders
Pain
|
28.6%
2/7 • Number of events 5 • Up to 6 years, 7 months
|
100.0%
3/3 • Number of events 4 • Up to 6 years, 7 months
|
15.4%
4/26 • Number of events 7 • Up to 6 years, 7 months
|
|
Cardiac disorders
Palpitations
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/7 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/7 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 2 • Up to 6 years, 7 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
57.1%
4/7 • Number of events 4 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
30.8%
8/26 • Number of events 8 • Up to 6 years, 7 months
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders
|
0.00%
0/7 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Runny Nose
|
0.00%
0/7 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Infections and infestations
Sinusitis
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
42.9%
3/7 • Number of events 3 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 2 • Up to 6 years, 7 months
|
11.5%
3/26 • Number of events 5 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
28.6%
2/7 • Number of events 2 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
General disorders
Sweats
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Nervous system disorders
Syncope
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/7 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/7 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Infections and infestations
Urinary tract infection
|
57.1%
4/7 • Number of events 5 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 3 • Up to 6 years, 7 months
|
|
Eye disorders
Uveitis
|
0.00%
0/7 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
3.8%
1/26 • Number of events 1 • Up to 6 years, 7 months
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
0.00%
0/7 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
2/7 • Number of events 2 • Up to 6 years, 7 months
|
0.00%
0/3 • Up to 6 years, 7 months
|
7.7%
2/26 • Number of events 2 • Up to 6 years, 7 months
|
|
Gastrointestinal disorders
Weight loss
|
14.3%
1/7 • Number of events 1 • Up to 6 years, 7 months
|
33.3%
1/3 • Number of events 1 • Up to 6 years, 7 months
|
0.00%
0/26 • Up to 6 years, 7 months
|
Additional Information
Nitin Jain, MD/Associate Professor
The University of Texas MD Anderson Cancer Center
Phone: 713-745-6080
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place