Front Line Ibrutinib Without Corticosteroids for Newly Diagnosed Chronic Graft-versus-Host Disease

Summary

Background:

\- Chronic Graft Versus Host Disease (cGVHD) can occur after a person has had a stem cell or bone marrow transplant. In cGVHD, the donor cells attack the recipient's body. Researchers want to see if a drug called ibrutinib can block one of the proteins that lead to the immune reaction that causes cGVHD.

Objective:

\- To see if ibrutinib as a first-line treatment can help people with newly diagnosed cGVHD.

Eligibility:

\- People age 18 and older with newly diagnosed moderate or severe cGVHD

Design:

* Participants will be screened with:
* Medical and medicine histories
* Physical exam and vital signs
* Electrocardiograms (to measure heart function)
* Assessment of their ability to perform daily activities
* Blood and urine tests
* Assessment of their general well-being.
* Participants will visit the Clinical Center every 2 weeks for the first 2 months. Then they will visit every 4 weeks.
* Participants will take ibrutinib by mouth once every day of every cycle. One cycle is 28 days. Treatment will last up to 2 years. Participants will keep a medicine diary.
* Participants will take tests to measure lung function. They may have computed tomography scans of their chest. They will complete questionnaires about their symptoms and how cGVHD is affecting their body and quality of life. They will repeat the screening tests.
* Participants may have optional blood tests and/or skin biopsies to better understand the drugs effect on the body.
* Participants will be contacted by phone 30 days after treatment ends. They will also be contacted once a year for 2 years to discuss how they are feeling and if they have taken any other medicines to treat cGVHD.

Conditions

• Chronic GVHD

Interventions

DRUG

Ibrutinib

140 mg capsules for a dose of 420 mg daily by mouth for up to 12 months.

DIAGNOSTIC_TEST

ECG

At screening.

DIAGNOSTIC_TEST

PFT's

Participants should have PFTs if not performed ≤3 months prior to start of study treatment and Cycle 7, Day 1 (6 months). Optional at Cycle 12, Day 28 (12 months) and Cycle 24, Day 28 (24 months).

DIAGNOSTIC_TEST

CT

Non-contrast CT at baseline and later during the study if clinically indicated.

DRUG

Steroid pulse (prednisone)

0.5-2mg/kg/day allowed for clinical disease stabilization during first 4 weeks after starting Ibrutinib.

DRUG

Voriconazole

At any dose.

DRUG

Posaconazole

As clinically indicated. At doses less than or equal to suspension 200 mg twice a day (BID) if ibrutinib dose modified to 280 mg once daily. OR Posaconazole suspension 200 mg three times a day (TID) or 400 mg BID if Ibrutinib dose modified to 140 mg once daily. OR Posaconazole injection intravenous (IV) injection 300 mg once daily; or delayed-release capsules 300 mg once daily if Ibrutinib dose modified to 140 mg once daily..

DRUG

Azithromycin

Treat or prevent bronchiolitis obliterans.

DRUG

Montelukast

Treat or prevent bronchiolitis obliterans.

DRUG

Budesonide

Treat or prevent gastrointestinal acute graft-versus host disease (GvHD).

DRUG

Beclomethasone

Treat or prevent gastrointestinal acute graft-versus host disease (GvHD).

OTHER

Filgrastim

Neutrophil growth factor permitted per institutional policy

OTHER

Pegfilgrastim

Neutrophil growth factor permitted per institutional policy.

OTHER

Erythropoietin

Red cell growth factor permitted per institutional policy.

OTHER

Transfusions

According to institutional policy.

PROCEDURE

Oral/Skin biopsy

Optional. Baseline, Cycle 7, Day 1 (6 months), Cycle 12, Day 28 (12 months) and Cycle 24, Day 28.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven Z Pavletic, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-05-10

Primary Completion

2024-06-24

Completion

2024-10-01

FDA Drug

Yes

Countries

• United States

Study Locations