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Low Recruitment
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| Name | Class |
|---|---|
| Pharmacyclics LLC. | INDUSTRY |
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This is a phase II trial evaluating the safety and efficacy of the combination of Ibrutinib and Rituximab as primary treatment of chronic GVHD. We plan to enroll 35 patients on this study. Patients will be formally monitored monthly for 12 months to evaluate for outcome and safety endpoints. All other assessments will be done at the physician's discretion or institutional standards. All patients, responders and treatment failures, will be followed for a period of one year from the time of initiation of therapy. The primary endpoint will be the proportion of patients that are alive and off all systemic IST at 12 months following initiation of treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rituximab + Ibrutinib | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rituximab | Drug | 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). |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Patients Who Remain Off Immunosuppressive Therapy at 12 Months After the Initiation of Treatment. | 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. | 12 months following initiation of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Patients Who Respond to Treatment Assessed by NIH Response Criteria Working Group Report. | To 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]) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Scott R Solomon, MD | Northside Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northside Hospital | Atlanta | Georgia | 30342 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Number of Patients Who Remain Off Immunosuppressive Therapy at 12 Months After the Initiation of Treatment. | 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. | Posted | Count of Participants | Participants | 12 months following initiation of treatment |
|
12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Right hepatic hematoma | Blood and lymphatic system disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 Infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Scott Solomon | The Blood and Marrow Transplant Group of Georgia | 404-255-1930 | ssolomon@bmtga.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 12, 2022 | Oct 16, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| D000092122 | Bronchiolitis Obliterans Syndrome |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D000092124 | Organizing Pneumonia |
| D001989 | Bronchiolitis Obliterans |
| D001988 | Bronchiolitis |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| C551803 | ibrutinib |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Ibrutinib | Drug | Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles. |
|
| 12 months following initiation of treatment |
| How Long it Takes for Patients to Discontinue Treatment Defined as the Date All Systemic Immunosuppressive Therapy is Discontinued After Resolution of GVHD. | To 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). | Up to 32 months |
| 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. | To estimate failure-free survival (defined as being alive without the requirement for second-line cGVHD therapy). | 12 months following initiation of treatment |
| How Many Patients Have Not Relapsed Measured by Progression-free Survival at 12 Months Following the Initiation of Treatment. | To estimate non-relapse mortality | 12 months following initiation of treatment |
| How Many Patients Have Not Died Measured by Overall Survival at 12 Months Following the Initiation of Treatment. | To estimate overall survival | 12 months following initiation of treatment |
| Number of Patients With Treatment-related Adverse Events Grade 3 or Greater as Assessed by CTCAE v.4.0. | To estimate the incidence of grade 3 or greater adverse events, possibly or probably related to either ibrutinib and/or rituximab. | 12 months following initiation of treatment |
| Number of Patients With Treatment-related Adverse Events Total as Assessed by CTCAE v.4.0. | To evaluate the safety and tolerability of combination of rituximab and ibrutinib versus the historical experience with rituximab alone in the upfront treatment of cGVHD. | 12 months following initiation of treatment |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | The Number of Patients Who Respond to Treatment Assessed by NIH Response Criteria Working Group Report. | To 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]) | Posted | Count of Participants | Participants | 12 months following initiation of treatment |
|
|
|
| Secondary | How Long it Takes for Patients to Discontinue Treatment Defined as the Date All Systemic Immunosuppressive Therapy is Discontinued After Resolution of GVHD. | To 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). | Posted | Median | Full Range | months | Up to 32 months |
|
|
|
| Secondary | 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. | To estimate failure-free survival (defined as being alive without the requirement for second-line cGVHD therapy). | Posted | Count of Participants | Participants | 12 months following initiation of treatment |
|
|
|
| Secondary | How Many Patients Have Not Relapsed Measured by Progression-free Survival at 12 Months Following the Initiation of Treatment. | To estimate non-relapse mortality | Posted | Count of Participants | Participants | 12 months following initiation of treatment |
|
|
|
| Secondary | How Many Patients Have Not Died Measured by Overall Survival at 12 Months Following the Initiation of Treatment. | To estimate overall survival | Posted | Count of Participants | Participants | 12 months following initiation of treatment |
|
|
|
| Secondary | Number of Patients With Treatment-related Adverse Events Grade 3 or Greater as Assessed by CTCAE v.4.0. | To estimate the incidence of grade 3 or greater adverse events, possibly or probably related to either ibrutinib and/or rituximab. | Posted | Count of Participants | Participants | 12 months following initiation of treatment |
|
|
|
| Secondary | Number of Patients With Treatment-related Adverse Events Total as Assessed by CTCAE v.4.0. | To evaluate the safety and tolerability of combination of rituximab and ibrutinib versus the historical experience with rituximab alone in the upfront treatment of cGVHD. | Posted | Count of Participants | Participants | 12 months following initiation of treatment |
|
|
|
| 2 |
| 15 |
| 4 |
| 15 |
| 15 |
| 15 |
| Right hepatic mass | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| CMV colitis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Fever | Investigations | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Increased ALT | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Increased AST | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypertension | Cardiac disorders | Non-systematic Assessment |
|
| Nose bleed | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Blurred vision | Eye disorders | Non-systematic Assessment |
|
| Skin tightness | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Bacteremia | Infections and infestations | Non-systematic Assessment |
|
| Mouth sores | Gastrointestinal disorders | Non-systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Hypergylcemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Anorexia | Gastrointestinal disorders | Non-systematic Assessment |
|
| Muscle pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Increased GGT | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Increased alkaline phosphatase | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Myalgias | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Right upper lip laceration | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Weight loss | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Hypomagnesemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Chest tightness | Cardiac disorders | Non-systematic Assessment |
|
| Chills | Infections and infestations | Non-systematic Assessment |
|
| Fever | Infections and infestations | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
|
| Hypotension | Cardiac disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Orthopnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Taste alterations | Gastrointestinal disorders | Non-systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Headache | General disorders | Non-systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | Non-systematic Assessment |
|
| Early satiety | Gastrointestinal disorders | Non-systematic Assessment |
|
| Anal pain | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dry eyes | Eye disorders | Non-systematic Assessment |
|
| Bruising | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Bilateral lower extremity edema | Cardiac disorders | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Non-systematic Assessment |
|
| C. diff infection | Infections and infestations | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
|
| Pharyngitis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Alopecia | General disorders | Non-systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | Non-systematic Assessment |
|
| Hypopigmentation | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Bilateral toe paronychia | Infections and infestations | Non-systematic Assessment |
|
| Cellulitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
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| D001991 |
| Bronchitis |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |