Ibrutinib and Rituxan for Chronic GVHD

Sponsor
Northside Hospital, Inc. (Other)
Overall Status
Recruiting
CT.gov ID
NCT04235036
Collaborator
Pharmacyclics LLC. (Industry)
35
Enrollment
1
Location
1
Arm
60.5
Anticipated Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Anticipated 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 :
Dec 16, 2019
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Dec 31, 2024

Arms and Interventions

ArmIntervention/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

Primary Outcome Measures

  1. The number of patients who remain off immunosuppressive therapy at 8 weeks after the initiation of treatment. [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. [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. [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. [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. [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. [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. [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. [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. [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

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

SiteCityStateCountryPostal Code
1Northside HospitalAtlantaGeorgiaUnited States30342

Sponsors and Collaborators

  • Northside Hospital, Inc.
  • Pharmacyclics LLC.

Investigators

  • Principal Investigator: Scott R Solomon, MD, Northside Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Northside Hospital, Inc.
ClinicalTrials.gov Identifier:
NCT04235036
Other Study ID Numbers:
  • NSH 1219
First Posted:
Jan 21, 2020
Last Update Posted:
Apr 5, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Northside Hospital, Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 5, 2022