Ibrutinib for the Prevention of Chronic Graft-Versus-Host Disease in Patients Undergoing Donor Stem Cell Transplant

NCT06271616 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: MC1873NCI-2024-0106118-008754
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well ibrutinib works in preventing chronic graft-versus-host disease (GVHD) in patients undergoing donor (allogeneic) hematopoietic cell transplantation (HCT). An allogeneic hematopoietic cell transplantation (allo-HCT) is a treatment in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical donor. When healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets. However, sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD). Giving ibrutinib after the transplant may stop that from happening. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking a protein in the blood called Bruton's tyrosine kinase (BTK). By blocking BTK, ibrutinib inhibits certain immune cells that play a role in cGVHD. Giving ibrutinib after an allo-HCT may prevent the development of chronic GVHD.

Conditions

Chronic Graft Versus Host Disease; Hematopoietic and Lymphatic System Neoplasm

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of NIH moderate/severe chronic graft-versus-host disease (GVHD)

  The cumulative incidence of National Institutes of Health (NIH) moderate/severe chronic GVHD will be estimated from the date of registration using a competing risk model, with death and relapse without NIH moderate/severe chronic GVHD as the competing risks.

  At 1 year post registration

Secondary Outcomes (11)

• Cumulative incidence of non-relapse mortality (NRM)

  Up to 1 year after last dose of study drug

• Cumulative incidence of relapse

  Up to 1 year after last dose of study drug

• Cumulative incidence of moderate/severe chronic GVHD

  Up to 1 year after last dose of study drug

• Cumulative incidence of moderate/severe chronic GVHD

  Up to 1 year after last dose of study drug

• Cumulative incidence of chronic GVHD of all grades

  Up to 1 year after last dose of study drug

Study Arms (1)

Prevention (ibrutinib)

EXPERIMENTAL

Patients receive ibrutinib PO QD on days 1-30 of each cycle. Cycles repeat every 30 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo an echocardiography prior to registration on study.

Procedure: Echocardiography Test; Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Prevention (ibrutinib)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Prevention (ibrutinib)

Eligibility Criteria

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

You may qualify if:

• to 110 days post-transplant prior to registration
• Age ≥ 18 years
• HLA matched-related, matched unrelated donors (defined as 8/8 \[class I: HLA A, B, C, and class II: DRB1\]), or HLA-mismatched-unrelated donors (defined as 7/8 \[with single mismatch at class I: HLA A, B, C, or class II: DRB1\])
• Karnofsky performance status (PS) ≥ 70
• Hemoglobin ≥ 8.0 g/dL (untransfused) (obtained ≤ 7 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1000/mm\^3 (without growth factor support) (obtained ≤ 7 days prior to registration)
• Platelet count ≥ 50,000/mm\^3 (untransfused) (obtained ≤ 7 days prior to registration)
• Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 7 days prior to registration)
• Total bilirubin ≤ 1.5 x ULN (unless it is due to Gilbert's syndrome or causes other than liver) OR alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2 x ULN (unless it is due to Gilbert's syndrome or causes other than liver) (obtained ≤ 7 days prior to registration)
• Calculated creatinine clearance ≥ 40 ml/min using the Cockcroft-Gault formula (obtained ≤ 7 days prior to registration)
• Adequate cardiac and pulmonary function at baseline (may be based on pre-transplant vital organ work up):
• Cardiac evaluation to determine left ventricular ejection fraction (LV-EF) if there is any clinical reason (for example an ischemic event or hypovolemic shock) to suspect that the LV-EF was affected from the time of the prior measurement of baseline (required ≥ 45%)
• Pulmonary evaluation to determine adequate pulmonary function with a diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 50% predicted value, forced expiratory volume in 1 second (FEV1) ≥ 50% predicted value and forced vital capacity (FVC) ≥ 50% predicted value
• Persons of childbearing potential must have negative serum pregnancy test ≤ 7 days prior to registration. Persons of non-reproductive potential are defined as follows: post-menopausal by history - no menses for ≥ 1 year; or status post (s/p) hysterectomy; or s/p bilateral tubal ligation; or history of bilateral oophorectomy
• All subjects agreeable to using both a highly effective method of birth control \[for example, implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), or sterilized partner\] and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug

You may not qualify if:

• Uncontrolled acute GVHD at time of registration.
• Note: Uncontrolled is defined as unable to tolerate tapering down of steroids or other therapies or requiring additional therapies or increase in doses of prescribed therapies
• Evidence of NIH chronic GVHD preceding registration or at time of registration
• Relapsed/progressive disease compared to prior to transplant and prior to registration. In this case, baseline represents the baseline disease staging (if no other disease staging has been performed prior to enrollment); or a post-transplant disease staging if that represents the most immediate staging prior to enrollment. In the event that both had been performed, the latest one performed (i.e. the one closest in time to the enrollment to this trial) will be considered the baseline for comparison.
• Note: Relapse and progression definitions for each hematologic malignancy/ disorder will follow standard definition
• Uncontrolled active systemic fungal, viral, bacterial, or other infection Note: Infections are considered controlled if appropriate therapy has been instituted and at the time of registration have no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection
• Unable to swallow capsules or impairment/disease significantly affecting gastrointestinal function that may significantly alter the absorption of the drugs (e.g., gastric bypass surgeries, Celiac or Whipple disease)
• Any of the following because this study involves) an agent that has known genotoxic, mutagenic and teratogenic effects:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• History of stroke or intracranial hemorrhage ≤ 6 months prior to registration
• Active involvement of the central nervous system with malignancy.
• Note: Previous central nervous system (CNS) involvement is allowed if clearance of CNS disease has been documented prior to registration
• Require anticoagulation with warfarin or other Vitamin K antagonists

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Officials

• Mohamed A. Kharfan Dabaja, MD, MBA

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

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

Study Record Dates

• First Submitted: February 14, 2024
• First Posted: February 22, 2024
• Study Start: December 13, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: December 26, 2025

Record last verified: 2025-12

Locations

US (1)