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Ibrutinib and Rituxan for Chronic GVHD

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ClinicalTrials.gov Identifier: NCT04235036
Recruitment Status : Recruiting
First Posted : January 21, 2020
Last Update Posted : August 31, 2021
Sponsor:
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Northside Hospital, Inc.

Study Description
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Brief 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. 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.

Condition or disease Intervention/treatment Phase
Graft Vs Host Disease Drug: Rituximab Drug: Ibrutinib Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 16, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2023

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Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: 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).

Drug: Ibrutinib
Ibrutinib is given orally every day (28-day cycles) for a total of 12 cycles.


Outcome Measures
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Primary Outcome Measures :
  1. The number of patients who remain off immunosuppressive therapy at 8 weeks 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 for at least 8 weeks.


Secondary Outcome Measures :
  1. The number of patients who respond to treatment assessed by NIH Response Criteria Working Group Report. [ Time Frame: 12 months following initiation of treatment ]
    To estimate chronic GVHD response (CR + PR, both individual organ response and overall response, according to 2014 NIH Response Criteria Working Group Report)

  2. The total cumulative steroid exposure measured by total milligrams received by each patient. [ Time Frame: 12 months following initiation of treatment ]
    To estimate cumulative steroid exposure (total mg methylprednisolone or equivalent)

  3. 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: 12 months following initiation of treatment ]
    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).

  4. 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 ]
    To estimate failure-free survival (defined as being alive without the requirement for second-line cGVHD therapy).

  5. 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 ]
    To estimate non-relapse mortality

  6. 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 ]
    To estimate overall survival

  7. 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 ]
    To estimate the incidence of grade 3 or greater adverse events, possibly or probably related to either ibrutinib and/or rituximab.

  8. Number of patients with treatment-related adverse events total as assessed by CTCAE v.4.0. [ Time Frame: 12 months following initiation of treatment ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04235036


Contacts
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Contact: Scott R Solomon, MD 404-255-1930 ssolomon@bmtga.com
Contact: Stacey Brown 404-780-7965 stacey.brown@northside.com

Locations
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United States, Georgia
Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Stacey Brown, BA    404-780-7965    stacey.brown@northside.com   
Contact: Caitlin Guzowski, MBA, MHA    404-851-8523    caitlin.guzowski@northside.com   
Sub-Investigator: H. Kent Holland, MD         
Sub-Investigator: Asad Bashey, MD         
Sub-Investigator: Lawrence E Morris, MD         
Sub-Investigator: Scott Solomon, MD         
Principal Investigator: Melhem Solh, MD         
Sponsors and Collaborators
Northside Hospital, Inc.
Pharmacyclics LLC.
Investigators
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Principal Investigator: Scott R Solomon, MD Northside Hospital
More Information
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Responsible Party: Northside Hospital, Inc.
ClinicalTrials.gov Identifier: NCT04235036    
Other Study ID Numbers: NSH 1219
First Posted: January 21, 2020    Key Record Dates
Last Update Posted: August 31, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Northside Hospital, Inc.:
ibrutinib
rituximab
cGVHD
chronic GVHD
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Rituximab
Antineoplastic Agents, Immunological
 Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents