Trial Outcomes & Findings for Ibrutinib and Rituxan for Chronic GVHD (NCT NCT04235036)
NCT ID: NCT04235036
Last Updated: 2024-12-13
Results Overview
The primary objective is to evaluate the efficacy of the combination of rituximab and ibrutinib versus the historical experience with rituximab alone in the upfront treatment of cGVHD. Patients will be followed for 12 months following the initiation of treatment to see if they remain off immunosuppressive therapy.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
15 participants
Primary outcome timeframe
12 months following initiation of treatment
Results posted on
2024-12-13
Participant Flow
Participant milestones
| Measure |
Rituximab + Ibrutinib
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Rituximab + Ibrutinib
n=15 Participants
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
Region of Enrollment
United States
|
15 participants
n=15 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=15 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=15 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=15 Participants
|
|
Age, Continuous
|
58 years
n=15 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=15 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=15 Participants
|
PRIMARY outcome
Timeframe: 12 months following initiation of treatmentThe primary objective is to evaluate the efficacy of the combination of rituximab and ibrutinib versus the historical experience with rituximab alone in the upfront treatment of cGVHD. Patients will be followed for 12 months following the initiation of treatment to see if they remain off immunosuppressive therapy.
Outcome measures
| Measure |
Rituximab + Ibrutinib
n=15 Participants
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
The Number of Patients Who Remain Off Immunosuppressive Therapy at 12 Months After the Initiation of Treatment.
|
4 Participants
|
SECONDARY outcome
Timeframe: 12 months following initiation of treatmentTo estimate chronic GVHD response (CR + PR, both individual organ response and overall response, according to 2014 NIH Response Criteria Working Group Report \[CR - resolution of all manifestations in each organ or site; PR - improvement in at least 1 organ or site without progression in any other organ or site\])
Outcome measures
| Measure |
Rituximab + Ibrutinib
n=15 Participants
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
The Number of Patients Who Respond to Treatment Assessed by NIH Response Criteria Working Group Report.
|
11 Participants
|
SECONDARY outcome
Timeframe: Up to 32 monthsTo estimate time to discontinuation of systemic immunosuppression (defined as the date that all systemic IST has been discontinued after resolution of all reversible manifestations of cGVHD).
Outcome measures
| Measure |
Rituximab + Ibrutinib
n=15 Participants
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
How Long it Takes for Patients to Discontinue Treatment Defined as the Date All Systemic Immunosuppressive Therapy is Discontinued After Resolution of GVHD.
|
15 months
Interval 0.0 to 31.0
|
SECONDARY outcome
Timeframe: 12 months following initiation of treatmentTo estimate failure-free survival (defined as being alive without the requirement for second-line cGVHD therapy).
Outcome measures
| Measure |
Rituximab + Ibrutinib
n=15 Participants
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
How Many Patients Are Still Alive Without the Requirement for Second-line cGVHD Therapy Measured by Overall Survival at 12 Months Following the Initiation of Treatment.
|
7 Participants
|
SECONDARY outcome
Timeframe: 12 months following initiation of treatmentTo estimate non-relapse mortality
Outcome measures
| Measure |
Rituximab + Ibrutinib
n=15 Participants
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
How Many Patients Have Not Relapsed Measured by Progression-free Survival at 12 Months Following the Initiation of Treatment.
|
11 Participants
|
SECONDARY outcome
Timeframe: 12 months following initiation of treatmentTo estimate overall survival
Outcome measures
| Measure |
Rituximab + Ibrutinib
n=15 Participants
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
How Many Patients Have Not Died Measured by Overall Survival at 12 Months Following the Initiation of Treatment.
|
13 Participants
|
SECONDARY outcome
Timeframe: 12 months following initiation of treatmentTo estimate the incidence of grade 3 or greater adverse events, possibly or probably related to either ibrutinib and/or rituximab.
Outcome measures
| Measure |
Rituximab + Ibrutinib
n=15 Participants
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
Number of Patients With Treatment-related Adverse Events Grade 3 or Greater as Assessed by CTCAE v.4.0.
|
9 Participants
|
SECONDARY outcome
Timeframe: 12 months following initiation of treatmentTo evaluate the safety and tolerability of combination of rituximab and ibrutinib versus the historical experience with rituximab alone in the upfront treatment of cGVHD.
Outcome measures
| Measure |
Rituximab + Ibrutinib
n=15 Participants
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
Number of Patients With Treatment-related Adverse Events Total as Assessed by CTCAE v.4.0.
|
13 Participants
|
Adverse Events
Rituximab + Ibrutinib
Serious events: 4 serious events
Other events: 15 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Rituximab + Ibrutinib
n=15 participants at risk
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
Blood and lymphatic system disorders
Right hepatic hematoma
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Blood and lymphatic system disorders
Right hepatic mass
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Gastrointestinal disorders
CMV colitis
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Investigations
Fever
|
6.7%
1/15 • Number of events 1 • 12 months
|
Other adverse events
| Measure |
Rituximab + Ibrutinib
n=15 participants at risk
Eligible patients will be those with a first episode of symptomatic cGVHD, requiring systemic immunosuppression for control of symptoms. Following study entry, patients will be started on rituximab plus ibrutinib.
Rituximab: Rituximab is given IV weekly x 4 weeks (to be started on study day 7 ± 3 days), then IV q3months x 4 doses (months 4, 7, 10, 13).
Ibrutinib: Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
COVID-19 Infection
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Gastrointestinal disorders
Vomiting
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
46.7%
7/15 • Number of events 7 • 12 months
|
|
Metabolism and nutrition disorders
Increased ALT
|
20.0%
3/15 • Number of events 3 • 12 months
|
|
Blood and lymphatic system disorders
Lymphopenia
|
60.0%
9/15 • Number of events 9 • 12 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
60.0%
9/15 • Number of events 9 • 12 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
53.3%
8/15 • Number of events 8 • 12 months
|
|
Metabolism and nutrition disorders
Increased AST
|
26.7%
4/15 • Number of events 4 • 12 months
|
|
Cardiac disorders
Hypertension
|
20.0%
3/15 • Number of events 3 • 12 months
|
|
Blood and lymphatic system disorders
Nose bleed
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
26.7%
4/15 • Number of events 4 • 12 months
|
|
Eye disorders
Blurred vision
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Skin and subcutaneous tissue disorders
Skin tightness
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Infections and infestations
Bacteremia
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Gastrointestinal disorders
Mouth sores
|
20.0%
3/15 • Number of events 3 • 12 months
|
|
Blood and lymphatic system disorders
Anemia
|
46.7%
7/15 • Number of events 7 • 12 months
|
|
Metabolism and nutrition disorders
Hypergylcemia
|
40.0%
6/15 • Number of events 6 • 12 months
|
|
Gastrointestinal disorders
Anorexia
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Muscle pain
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Metabolism and nutrition disorders
Increased GGT
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
20.0%
3/15 • Number of events 3 • 12 months
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
20.0%
3/15 • Number of events 3 • 12 months
|
|
Gastrointestinal disorders
Nausea
|
33.3%
5/15 • Number of events 5 • 12 months
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Metabolism and nutrition disorders
Increased alkaline phosphatase
|
20.0%
3/15 • Number of events 3 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Myalgias
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Skin and subcutaneous tissue disorders
Right upper lip laceration
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Metabolism and nutrition disorders
Weight loss
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
20.0%
3/15 • Number of events 3 • 12 months
|
|
Cardiac disorders
Chest tightness
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Infections and infestations
Chills
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Infections and infestations
Fever
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Gastrointestinal disorders
Constipation
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Cardiac disorders
Hypotension
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Gastrointestinal disorders
Diarrhea
|
26.7%
4/15 • Number of events 4 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Orthopnea
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
26.7%
4/15 • Number of events 4 • 12 months
|
|
Gastrointestinal disorders
Taste alterations
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
General disorders
Fatigue
|
20.0%
3/15 • Number of events 3 • 12 months
|
|
General disorders
Headache
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Cardiac disorders
Pericardial effusion
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Gastrointestinal disorders
Early satiety
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Gastrointestinal disorders
Anal pain
|
6.7%
1/15 • Number of events 2 • 12 months
|
|
Eye disorders
Dry eyes
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Blood and lymphatic system disorders
Bruising
|
20.0%
3/15 • Number of events 3 • 12 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
13.3%
2/15 • Number of events 2 • 12 months
|
|
Cardiac disorders
Bilateral lower extremity edema
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Infections and infestations
Urinary tract infection
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Infections and infestations
C. diff infection
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Gastrointestinal disorders
Pharyngitis
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
General disorders
Alopecia
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Renal and urinary disorders
Urinary frequency
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Skin and subcutaneous tissue disorders
Hypopigmentation
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Infections and infestations
Bilateral toe paronychia
|
6.7%
1/15 • Number of events 1 • 12 months
|
|
Skin and subcutaneous tissue disorders
Cellulitis
|
6.7%
1/15 • Number of events 1 • 12 months
|
Additional Information
Dr. Scott Solomon
The Blood and Marrow Transplant Group of Georgia
Phone: 404-255-1930
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place