Trial Title:
Ibrutinib for the Prevention of Chronic Graft-Versus-Host Disease in Patients Undergoing Donor Stem Cell Transplant
NCT ID:
NCT06271616
Condition:
Chronic Graft Versus Host Disease
Hematopoietic and Lymphatic System Neoplasm
Conditions: Official terms:
Bronchiolitis Obliterans Syndrome
Graft vs Host Disease
Ibrutinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Prevention (ibrutinib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo echocardiography
Arm group label:
Prevention (ibrutinib)
Other name:
EC
Intervention type:
Drug
Intervention name:
Ibrutinib
Description:
Given PO
Arm group label:
Prevention (ibrutinib)
Other name:
BTK Inhibitor PCI-32765
Other name:
CRA-032765
Other name:
Imbruvica
Other name:
PCI-32765
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.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the efficacy of ibrutinib in reducing the incidence of National Institutes
of Health (NIH) moderate/severe chronic GVHD by 1-year post-registration. (Phase II
Trial)
SECONDARY OBJECTIVES:
I. To determine the safety of ibrutinib when prescribed as prophylaxis for chronic GVHD.
II. To determine the cumulative incidence of non-relapse mortality (NRM). III. To
determine the cumulative incidence of relapse (CIR). IV. To determine the cumulative
incidence of chronic GVHD (moderate/severe and all grades).
V. To determine the cumulative incidence of late acute GVHD (LA GVHD). VI. To determine
1-year overall survival (OS) from time of transplantation. VII. To determine NIH
moderate/severe chronic GVHD and relapse free survival (CRFS).
VIII. To determine immune suppressive therapy required for therapy of chronic GVHD.
IX. To determine the cumulative incidence of complete immune suppression (IS)
discontinuation.
CORRELATIVE OBJECTIVES:
I. To describe immune reconstitution post-transplant through serial measure of immune
cell subsets and quantitative immunoglobulins.
II. To determine the efficiency of B-cell receptor (BCR) signaling blockades using
multiparameter time of flight cytometry (CyTOF) that has been optimized for BTK and
IL2-inducible T-cell kinase (ITK) phosphorylation assessment.
III. To investigate development of allogeneic antibodies and alloantigen specific B cells
in F-M patients before and after ibrutinib.
IV. To investigate the effects ibrutinib treatment on development of allogeneic B cells.
OUTLINE:
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-30 of each cycle. Cycles
repeat every 30 days for up to 12 cycles on study. Additionally, patients undergo an
echocardiography prior to registration and blood sample collection throughout study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 50 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
- Provide written informed consent
- Willingness to provide mandatory blood specimens for correlative research
- Willingness to return to enrolling institution for follow-up (during the active
monitoring phase of the study). Note: During the active monitoring phase of a study
(i.e., active treatment and clinical follow-up), participants must be willing to
return to the consenting institution for follow-up
Exclusion Criteria:
- 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
- Any of the following prior therapies:
- Administration of anti-thymocyte globulin (or equivalent), alemtuzumab, or post
transplant cyclophosphamide as part of the conditioning regimen or ≤ 1 month of
allograft. Patients must not have received T-cell depletion or CD-34 selection
- Administration of a strong cytochrome P450 (CYP) 3A inhibitor ≤ 7 days prior to
the first dose or subjects who require continuous treatment with a strong CYP3A
inhibitor
- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens
- Patients known to have tested positive on HIV antibody test
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance
with study requirements
- Chronic liver disease with hepatic impairment Child Pugh class B or C
- Active hepatitis B or C infection. Note: A detailed assessment of hepatitis B/C
medical history and risk factors must be done at screening for all patients.
hepatitis B immunoglobulin M antibody (HBcIgM Ab), hepatitis B surface antigen
(HBsAg) and hepatitis C virus antibody (HCV Ab) screen (scrn) w/reflex testing are
required at screening for all patients with a positive medical history based on risk
factors and/or confirmation of prior hepatitis B virus (HBV) infection
- Receiving any chemotherapy, anticancer immunotherapy, experimental therapy, or
radiotherapy is prohibited while the subject is receiving study treatment with
ibrutinib. The sponsor-investigator must be notified in advance (or as soon as
possible thereafter) of any instances in which prohibited therapies are
administered. EXCEPTIONS: Patients will be allowed to receive antimicrobial
prophylaxis appropriate for allogeneic HCT recipients, according to institutional
standards of practice (SOP) or common clinical practice
- Other active malignancy ≤ 5 years prior to registration. EXCEPTIONS: Non-melanotic
skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of prior
malignancy, they must not be receiving other treatment for their cancer
- History of myocardial infarction ≤ 6 months, or uncontrolled cardiac arrhythmias
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Mohamed A. Kharfan Dabaja, M.D., M.B.A.
Email:
Principal Investigator
Start date:
November 1, 2024
Completion date:
June 30, 2027
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06271616
https://www.mayo.edu/research/clinical-trials
