What is the mechanism of action of this treatment?

Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, works by blocking a protein that plays a crucial role in the immune response, thereby reducing the immune system's attack on the recipient's body in chronic Graft-versus-Host Disease (cGVHD). This is significant for GVHD patients as it helps to mitigate the immune-mediated damage to tissues and organs. Other common treatments include corticosteroids, which suppress the overall immune response, and immunosuppressive agents like cyclosporine and tacrolimus, which inhibit T-cell activation. These mechanisms are vital as they help to control the overactive immune response, reducing inflammation and preventing further tissue damage in GVHD patients.

What side effects are associated with this type of intervention?

Common treatments for Graft-versus-Host Disease (GVHD) include corticosteroids, calcineurin inhibitors (such as cyclosporine and tacrolimus), and monoclonal antibodies (like rituximab). Corticosteroids can cause side effects such as increased infection risk, high blood sugar, and bone thinning. Calcineurin inhibitors may lead to kidney toxicity, high blood pressure, and neurological symptoms. Monoclonal antibodies can result in infusion reactions, increased infection risk, and cytopenias. Ibrutinib, which is being studied for cGVHD, can cause side effects including diarrhea, fatigue, and an increased risk of bleeding and infections.

What prior FDA approvals exist?

Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has been approved by the FDA for the treatment of chronic Graft-versus-Host Disease (cGVHD) after failure of one or more lines of systemic therapy. This approval is based on its ability to block proteins involved in the immune reaction causing cGVHD. Other drugs that have been approved for GVHD include corticosteroids and immunosuppressive agents like cyclosporine and tacrolimus, which are used to manage the immune response. Additionally, ruxolitinib, a Janus kinase (JAK) inhibitor, has been approved for steroid-refractory acute GVHD, highlighting the trend towards targeted therapies in managing GVHD.

What other types of research exist?

Promising novel alternatives to Ibrutinib for treating Graft-versus-Host Disease (GVHD) include Bruton tyrosine kinase inhibitors (BTKi) like acalabrutinib and zanubrutinib, as well as anti-CD20 monoclonal antibodies such as Rituximab. Additionally, FcRn blockers like SYNT001 are emerging as potential options based on their efficacy in autoimmune conditions.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Ibrutinib for Chronic Graft-versus-Host Disease

Phase 2

Waitlist Available

Led By Steven Z Pavletic, M.D.

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

History of prior allogeneic Hematopoietic Stem Cell Transplant (HSCT) (any donors, conditioning regimens and graft sources are allowed)

Newly diagnosed moderate or severe chronic Graft versus Host Disease (GvHD) (according to the 2014 NIH Consensus Criteria, requiring systemic immunosuppression)

Must not have

Uncontrolled infections or bleeding disorder

Relapsed or progressive malignant disease (other than minimal residual disease)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ibrutinib, a pill that blocks a protein causing harmful immune reactions, in adults with newly diagnosed moderate or severe chronic graft-versus-host disease (cGVHD). The goal is to see if this drug can help control the disease by reducing the immune system's attack on the body. Ibrutinib was the first agent approved by the U.S. Food and Drug Administration for the treatment of chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.

Who is the study for?

Adults over 18 with newly diagnosed moderate or severe chronic Graft-versus-Host Disease after a stem cell or bone marrow transplant can join. They must be responding to current treatments, agree to use birth control, and have no uncontrolled infections, bleeding disorders, other cancers (with some exceptions), heart issues, hepatitis B/C, or known allergy to Ibrutinib.

What is being tested?

The trial is testing if Ibrutinib can help as a first-line treatment for cGVHD without needing steroids. Participants will take the drug daily for up to two years and attend regular check-ups including physical exams and lung function tests while keeping a medicine diary.

What are the potential side effects?

Ibrutinib may cause side effects such as diarrhea, muscle pain, rash, fever; it might also affect blood counts leading to increased bruising or risk of infection. Heart rhythm problems are possible too.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had a stem cell transplant from a donor.

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I have been newly diagnosed with moderate or severe chronic GvHD and need systemic immunosuppression.

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I am 18 years old or older.

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I can care for myself but may need occasional help.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any uncontrolled infections or bleeding disorders.

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My cancer has returned or worsened.

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I have severe liver problems (Child-Pugh class C).

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I have been treated for chronic GvHD with drugs other than a specific dose of prednisone.

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My heart does not function properly.

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I have hepatitis B or C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To evaluate the efficacy of ibrutinib as a first-line treatment for persons with newly diagnosed chronic graft-versus-host disease (GvHD) by measuring the overall response rate

Secondary study objectives

To evaluate 24 months post-treatment follow-up for survival

To evaluate failure-free survival (FFS)

To evaluate safety of ibrutinib for newly diagnosed chronic GvHD

Side effects data

From 2022 Phase 3 trial • 201 Patients • NCT03053440

37%

Diarrhoea

32%

Upper respiratory tract infection

29%

Muscle spasms

28%

Contusion

24%

Arthralgia

24%

Hypertension

22%

Oedema peripheral

22%

Anaemia

21%

Epistaxis

20%

Cough

19%

Rash

19%

Fatigue

18%

Back pain

18%

Atrial fibrillation

17%

Urinary tract infection

16%

Neutropenia

16%

Thrombocytopenia

15%

Nausea

15%

Headache

15%

Vomiting

14%

Pneumonia

14%

Dizziness

13%

Haematuria

12%

Peripheral swelling

12%

Pyrexia

12%

Constipation

11%

Localised infection

10%

Pain in extremity

10%

Onychoclasis

10%

Fall

10%

Oropharyngeal pain

10%

Lower respiratory tract infection

10%

Sinusitis

10%

Palpitations

Insomnia

Nasopharyngitis

Hyperuricaemia

Dyspnoea

Haematoma

Skin laceration

Paraesthesia

Dyspepsia

Dry skin

Cellulitis

Conjunctivitis

Skin infection

Iron deficiency

Anxiety

Rhinitis

Cataract

Conjunctival haemorrhage

Pruritus

Hypokalaemia

Syncope

Vision blurred

Abdominal pain

Abdominal pain upper

Nail infection

Neck pain

Purpura

Asthenia

Abdominal discomfort

Chest pain

Gingival bleeding

Mouth ulceration

Stomatitis

Onychomycosis

Rhinorrhoea

Actinic keratosis

Dermatitis

Petechiae

Influenza like illness

COVID-19

Gastroenteritis

Tooth infection

Limb injury

Squamous cell carcinoma of skin

Peripheral sensory neuropathy

Rosacea

Increased tendency to bruise

Gout

Basal cell carcinoma

Folliculitis

Oral herpes

Gastrooesophageal reflux disease

Retinal haemorrhage

Angina pectoris

Dry mouth

Vertigo

Haemorrhoids

Ecchymosis

Sepsis

Chills

Bronchitis

Furuncle

Joint injury

Blood alkaline phosphatase increased

Neutrophil count decreased

Decreased appetite

Joint swelling

Depression

Productive cough

Skin ulcer

Atrial flutter

Hyperglycaemia

Herpes zoster

Abdominal distension

Tinnitus

Bladder transitional cell carcinoma

Rotator cuff syndrome

Sinus bradycardia

Inguinal hernia

Dysphagia

Dry eye

Dysuria

Pollakiuria

Hypoalbuminaemia

Osteoporosis

Erythema

Acute myocardial infarction

Malaise

Cystitis

Alanine aminotransferase increased

Gamma-glutamyltransferase increased

Musculoskeletal chest pain

Seborrhoeic keratosis

Neuralgia

Benign prostatic hyperplasia

Dyspnoea exertional

Nasal congestion

Pneumonitis

Psoriasis

Skin fissures

Skin lesion

Laryngitis

Respiratory tract infection

Bradycardia

Acute kidney injury

Wound infection

Myalgia

Skin toxicity

Ear infection

Paronychia

Osteoarthritis

Pericarditis

Sciatica

Ocular hyperaemia

Nail disorder

Pleural effusion

Rectal haemorrhage

Cholecystitis

COVID-19 pneumonia

Drug withdrawal syndrome

Seasonal allergy

Vitamin D deficiency

Rash maculo-papular

Hypotension

Death

Loss of consciousness

Post procedural haemorrhage

Laryngeal oedema

Stress fracture

Lumbar vertebral fracture

Haemolytic anaemia

Haemorrhagic disorder

Viral infection

Wound infection staphylococcal

Cardiac failure acute

Wheezing

Colitis

Oral blood blister

Upper gastrointestinal haemorrhage

Drug-induced liver injury

Bacterial sepsis

Brain abscess

Device related infection

Gastrointestinal infection

Neurocryptococcosis

Septic shock

Streptococcal bacteraemia

Femoral neck fracture

Femur fracture

Subdural haematoma

Lethargy

Subarachnoid haemorrhage

Chronic kidney disease

Urinary bladder haemorrhage

Prostatitis

Acute pulmonary oedema

Hyponatraemia

Muscular weakness

Rash erythematous

Hyperviscosity syndrome

Melaena

Clostridium difficile infection

Post procedural sepsis

Pyelonephritis

Cerebrovascular accident

Respiratory disorder

Lymphadenopathy

Streptococcal sepsis

Amyloidosis

Influenza

Pneumonia viral

Coronary artery disease

Pericardial haemorrhage

Urosepsis

Spinal stenosis

100%

80%

60%

40%

20%

Study treatment Arm

Arm A: Ibrutinib

Arm B: Zanubrutinib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: InterventionExperimental Treatment1 Intervention

Determine response rate via continuous daily dose by mouth to determine efficacy

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ibrutinib

2014

Completed Phase 4

~2060

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, works by blocking a protein that plays a crucial role in the immune response, thereby reducing the immune system's attack on the recipient's body in chronic Graft-versus-Host Disease (cGVHD). This is significant for GVHD patients as it helps to mitigate the immune-mediated damage to tissues and organs. Other common treatments include corticosteroids, which suppress the overall immune response, and immunosuppressive agents like cyclosporine and tacrolimus, which inhibit T-cell activation. These mechanisms are vital as they help to control the overactive immune response, reducing inflammation and preventing further tissue damage in GVHD patients.