Graft Vs Host DiseasePhase 2NCT04235036
Ibrutinib and Rituxan for Chronic GVHD
A Phase 2 study testing Rituximab and Ibrutinib in people with Graft Vs Host Disease, run by Northside Hospital, Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Vs Host Disease
- What is being tested?
- Rituximab and Ibrutinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Dec 2019to 23 Dec 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- First episode of systemic immunosuppression-requiring cGVHD, defined as classic or overlap cGVHD by the NIH consensus criteria.
- Previously untreated cGVHD, defined by having received <10 days of corticosteroids or alternative systemic immunosuppressive agent started specifically for a new diagnosis of cGVHD.
- KPS 70% or greater
Who cannot join
- Late persistent or recurrent acute GVHD
- Active uncontrolled infection
- History of HIV infection; active HBV or HCV infection
- Inability to tolerate oral medications
- Progressive or recurrent malignancy following allogeneic transplant
- Exposure to BTK inhibitor following transplant
- Received prior treatment with ECP for cGVHD
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial Evaluating the Safety and Efficacy of Combined CD20- and BTK-Targeted B Cell Depleting Therapy With Rituximab and Ibrutinib in the Primary Treatment of Chronic Graft-Versus-Host Disease
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.
- Conditions
- Graft Vs Host Disease
- Keywords
- ibrutinib, rituximab, cGVHD, chronic GVHD
- Medical subject headings
- Graft vs Host Disease, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
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).
IbrutinibDrug
Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Rituximab; Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months following initiation of treatment
Secondary outcomes (7)
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])
Measured: 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).
Measured: 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).
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 12 months following initiation of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2020
- Study start16 Dec 2019
- Primary completion23 Dec 2022
- Study completion23 Dec 2022
Why it stopped: Low Recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft Vs Host DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northside Hospital, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Responsible party
- Sponsor
- Investigators
- Scott R Solomon, MD, Principal investigator, Northside Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04235036
- Sponsor's protocol ID
- NSH 1219
- Status last verified
- Dec 2024
- First submitted
- 19 Aug 2019
- Last updated
- 13 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Evaluating the Safety and Efficacy of Combined CD20- and BTK-Targeted B Cell Depleting Therapy With Rituximab and Ibrutinib in the Primary Treatment of Chronic Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT04235036
- Acronym / sponsor ID
- NSH 1219
- Conditions
- Graft Vs Host Disease
- Keywords
- ibrutinib, rituximab, cGVHD, chronic GVHD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Recruitment
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Northside Hospital, Inc.University, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Study start
- 16 Dec 2019 (actual)
- Primary completion
- 23 Dec 2022 (actual)
- Study completion
- 23 Dec 2022 (actual)
- First posted
- 21 Jan 2020 (actual)
- Results
- Posted 13 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab + Ibrutinib | Experimental | Drug: Rituximab, Drug: IbrutinibEligible 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- First episode of systemic immunosuppression-requiring cGVHD, defined as classic or overlap cGVHD by the NIH consensus criteria.
- Previously untreated cGVHD, defined by having received <10 days of corticosteroids or alternative systemic immunosuppressive agent started specifically for a new diagnosis of cGVHD.
- KPS 70% or greater
Key exclusion criteria (7 listed)
- Late persistent or recurrent acute GVHD
- Active uncontrolled infection
- History of HIV infection; active HBV or HCV infection
- Inability to tolerate oral medications
- Progressive or recurrent malignancy following allogeneic transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabRituximab 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). | Drug | Rituximab + Ibrutinib |
| IbrutinibIbrutinib is given orally every day (28-day cycles) for a total of 12 cycles. | Drug | Rituximab + Ibrutinib |
Primary outcome
The Number of Patients Who Remain Off Immunosuppressive Therapy at 12 Months After the Initiation of Treatment.
Time frame: 12 months following 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.
7 secondary outcomes
The Number of Patients Who Respond to Treatment Assessed by NIH Response Criteria Working Group Report.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 12 months following initiation of treatment
How Many Patients Have Not Died Measured by Overall Survival at 12 Months Following the Initiation of Treatment.
Time frame: 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.
Time frame: 12 months following initiation of treatment
Number of Patients With Treatment-related Adverse Events Total as Assessed by CTCAE v.4.0.
Time frame: 12 months following initiation of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott R Solomon, MD principal investigator
Northside Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab and Ibrutinib in people with Graft Vs Host Disease, run by Northside Hospital, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Patients Who Remain Off Immunosuppressive Therapy at 12 Months After the Initiation of Treatment. (time frame: 12 months following initiation of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2024.