Abatacept to Treat Steroid Refractory Chronic Graft Versus Host Disease (cGVHD)

Chronic Graft Versus Host Disease Clinical Trial

Official title: A Phase I Study of Abatacept in the Treatment of Patients With Steroid Refractory Chronic Graft Versus Host Disease (cGVHD)

Status Completed

Clinical Trial Summary

The participant is invited to take part in this study because they have chronic Graft versus Host Disease (cGVHD) that is not responding to standard treatment with steroids. This research study is a way of gaining new knowledge about the treatment of patients with cGVHD. This research study is evaluating a drug called abatacept.

Abatacept is a drug that alters and suppresses the immune system. Abatacept is approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe active rheumatoid arthritis in adults and of severe juvenile idiopathic arthritis (JIA) in patients who have failed prior therapy with disease-modifying anti-rheumatic drugs (DMARDs). These are autoimmune conditions, ie caused by an overactive immune system that attacks normal tissues and organs. It is currently being tested in a variety of other autoimmune conditions. In this case it is considered experimental.

cGVHD is caused by the donor cells attacking various organs of the recipient. The investigators try to minimize this immune attack by using corticosteroids such as prednisone. In severe cases prednisone is not sufficient and other immunosuppressive medications are used in addition in order to more efficiently control cGVHD and to limit the dose and consequently the multiple side-effects of corticosteroids. This study is being done to determine if the use of abatacept is safe in patients with cGVHD and if it can facilitate a better control of cGVHD.

During this study the participants will be evaluated for side effects from the treatment with abatacept, and for response of the cGVHD to the treatment. There will be two groups of participants in the study. The first group will be treated at a relatively low dose of abatacept. If this is found to be safe then the second group will be treated at a higher dose. Three to four tablespoons of blood will be drawn at every 2 week visit in order to determine your blood counts, kidney and liver function. Some of the blood will be used in a research lab in order to study measures of your immune system and how they might be affected by the treatment.

Clinical Trial Description

Before the research starts (screening): After signing the consent form, the participant will be asked to undergo some screening tests or procedures to find out if they can be in the research study. Many of these tests and procedures are likely to be part of regular cGVHD care and may be done even if it turns out that the participant does not take part in the research study. If the participant has had some of these tests or procedures recently, they may or may not have to be repeated.

• Complete Medical History and Physical Examination

• Blood Collection: 3-4 tablespoons of blood will be drawn to measure the participants complete blood counts, kidney, liver and thyroid function

• Disease Assessment: Depending on what organs are affected by their cGVHD the participant may undergo blood tests or a skin exam or an eye exam or a dental exam.

• Electrocardiogram (EKG): a noninvasive test that measures the electrical activity of the participant's heart

• A tuberculin skin test and a quantiferon blood test to rule out tuberculosis

• Pregnancy testing if applicable

• HIV and Hepatitis blood test: 2-3 teaspoons of blood will be collected to perform an HIV test. The participant will be asked to sign a separate consent form for this test. The participant's doctor will discuss the results of this test with the participant and the results will become a part of their permanent medical record. The participant may seek private HIV testing prior to consenting, and based on the results may choose whether or not to participate in this study or have the HIV test become part of their medical records.

If these tests show that the participant is eligible to participate in the research study, the participant will begin the study treatment. If the participant does not meet the eligibility criteria, the participant will not be able to participate in this research study.

Additional research procedures to be performed at the time of screening:

• Research blood testing: to study measures of the participant's immune system

After the screening procedures confirm that the participant is eligible to participate in the research study:

• Since the investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have abatacept, not everyone who participates in this research study will receive the same dose of the study drug. The dose the participant gets will depend on the number of participants who have been enrolled in the study before the participant and how well they have tolerated their doses.

• The total duration of treatment on this study is approximately 113 days or 6 treatments. Doses 1-3 will be administered every two weeks. One month following Dose 3, abatacept will be administered every four weeks for the remaining three doses (Doses 4-6.) The treatment will be given intravenously on these days. One month following your last dose of treatment, the participant will be seen in clinic. The participant will be seen in the clinic weekly through dose 4, then every 2 weeks for follow up even if the participant doesn't have treatment.

• The first group of participants will be treated with a lower dose of abatacept. If this dose is determined to be safe then the second group will be treated at a higher dose.

During treatment the participant will be seen in the clinic every two weeks. At every visit the following will be performed:

• Complete Medical History and Physical Examination

• Blood Collection: 3-4 tablespoons of blood will be drawn to measure their complete blood counts, kidney, liver and thyroid function

• Research blood testing: to study measures of the participant's immune system

• On the days of treatment the participant will undergo an assessment of cGVHD depending on what organs are affected

After the final dose of the study drug:

After the participant has completed taking the drug on the study, the following procedures and tests will take place:

• Safety assessment 28 days after the last dose of the study drug.

• Complete Medical History and Physical Examination

• Blood Collection: 3-4 tablespoons of blood will be drawn to measure the participant's complete blood counts, kidney, liver and thyroid function

• Disease Assessment: by physical exam and blood tests if the participant has leukemia or multiple myeloma, or physical exam and PET/CT or CT scan if the participant has lymphoma. These will be done at the safety assessment visit and at the 3 and 6 month follow up visits.

• Electrocardiogram

• Research blood testing: to study measures of your immune system

• Once the participant has completed treatment on study they will be followed monthly for 6 months ;

Related Conditions & MeSH terms

• Bronchiolitis Obliterans Syndrome
• Chronic Graft Versus Host Disease
• Graft vs Host Disease

• NCT number: NCT01954979
• Study type: Interventional
• Source: Beth Israel Deaconess Medical Center
• Status: Completed
• Phase: Phase 1
• Start date: March 27, 2014
• Completion date: January 16, 2024