Ibrutinib and Rituxan for Chronic GVHD

NCT04235036 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: NSH 1219
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft Vs Host Disease

Keywords

ibrutinib; rituximab; cGVHD; chronic GVHD

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• The Number of Patients Who Respond to Treatment Assessed by NIH Response Criteria Working Group Report.

  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.

  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.

  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.

  12 months following initiation of treatment

• How Many Patients Have Not Died Measured by Overall Survival at 12 Months Following the Initiation of Treatment.

  12 months following initiation of treatment

Study Arms (1)

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.

Drug: Rituximab; Drug: Ibrutinib

Interventions

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).

Rituximab + Ibrutinib

Ibrutinib DRUG

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

Rituximab + Ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northside Hospital, Inc.: lead
• Pharmacyclics LLC.: collaborator

Study Sites (1)

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease; Bronchiolitis Obliterans Syndrome

Interventions

Rituximab; ibrutinib

Condition Hierarchy (Ancestors)

Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Scott Solomon
• Organization: The Blood and Marrow Transplant Group of Georgia

ssolomon@bmtga.com

404-255-1930

Study Officials

• Scott R Solomon, MD

  Northside Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: January 21, 2020
• Study Start: December 16, 2019
• Primary Completion: December 23, 2022
• Study Completion: December 23, 2022
• Last Updated: December 13, 2024
• Results First Posted: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)