A Phase I Study of Abatacept in the Treatment of Patients With Steroid Refractory Chronic Graft Versus Host Disease (cGVHD)
Phase: Phase 1
NCT ID: NCT01954979
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-358
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.
Beth-Israel Deaconess Medical Center, Dana-Farber Cancer Institute
Jacalyn Rosenblatt, MD,
Beth Israel Deaconess Medical Center
Beth-Israel Deaconess Medical Center:
Cancer Trials Call Center, 617-667-3060
Participants must meet the following criteria on screening examination to be eligible to
participate in the study:
- Participants must be recipients of an allogeneic bone marrow or stem cell
transplantation with myeloablative or reduced intensity conditioning regimens.
- Participants must be at least 100 days after the transplantation or a donor
- Participants must have cGVHD (as defined by the National Institutes of Health
Consensus Development Project on Criteria for Clinical Trials in Chronic
- Participants may have either extensive or limited cGVHD requiring systemic treatment
- Participants must have steroid refractory cGVHD, defined as having persistent signs
and symptoms of chronic GVHD despite the use of prednisone at ≥ 0. 5 mg/kg/day (or
equivalent) for at least 4 weeks in the preceding 12 months. Patients may remain on
steroids while enrolled in the study.
- No addition or subtraction of other immunosuppressive medications for at least 4
weeks prior to starting treatment.
- On stable immunosuppressive regimen for 2 weeks prior to enrollment. Adjustment of
immunosuppressive medications to maintain a therapeutic level is permitted.
- Age ≥ 18 years at the time of signing the informed consent form.
Reproductive Status: Definition of Women of Child-Bearing Potential (WOCBP). WOCBP
comprises women who have experienced menarche and who have not undergone successful
surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)
or who are not post-menopausal (see definition below).
Post-menopause is defined as:
- Women who have had amenorrhea for ≥ 12 consecutive months (without another cause) and
who have a documented serum follicle-stimulating hormone (FSH) level > 35 mIU/mL.
- Women who have irregular menstrual periods and a documented serum FSH level > 35
- Women who are taking hormone replacement therapy (HRT).
The following women are WOCBP:
- Women using the following methods to prevent pregnancy: Oral contraceptives, other
hormonal contraceptives (vaginal products, skin patches, or implanted or injectable
products), or mechanical products such as intrauterine devices or barrier methods
(diaphragm, condoms, spermicides).
- Women who are practicing abstinence.
- Women who have a partner who is sterile (eg, due to vasectomy). WOCBP must be using
an acceptable method of contraception to avoid pregnancy throughout the study and for
up to 10 weeks after the last dose of study drug in such a manner that the risk of
pregnancy is minimized.
- WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity
25 IU/L or equivalent units of HCG) within 0 to 48 hours before the first dose of
- Women must not be breast-feeding.
- Sexually active fertile men must use effective birth control if their partners are
- Life expectancy of greater than > 3 months.
- ECOG performance status ≤ 2 (see Appendix A).
- Laboratory test results within these ranges:
- Absolute neutrophil count ≥ 1500/mm³
- Serum creatinine ≤ 2.0 mg/dL
- Renal function assessed by calculated creatinine clearance ≥ 60ml/min by
Cockcroft-Gault formula (see Appendix B: Cockcroft-Gault estimation of CrCl).
- Total bilirubin ≤ 1.5 x ULN (unless hepatic dysfunction is caused by cGVHD)AST (SGOT)
and ALT (SGPT) ≤ 3 x ULN (unless hepatic dysfunction is caused by cGVHD).
- Patients much have a negative PPD skin test and a negative Quantiferon assay.
- Must possess the ability to understand and the willingness to sign a written informed
- Participants who exhibit any of the following conditions at screening will not be
eligible for admission into the study.
- Any serious medical condition (including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia), laboratory abnormality, or psychiatric illness/ social situation that
would prevent the subject from signing the informed consent form or limit compliance
with study requirements.
- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.
- Use of any other experimental drug or therapy within 28 days of starting treatment
- Use of biologic antibody therapy for cGVHD with rituximab, alemtuzumab, or ATG within
6 months of starting treatment with abatacept.
- Use of TNF alpha inhibitors within four weeks prior to study entry.
- Ongoing prednisone requirement >1 mg/kg/day (or equivalent)
- New immunosuppressive medication or ECP within 28 days of starting treatment with
- Donor lymphocyte infusion within 100 days prior to enrollment.
- Active malignant disease relapse or other active malignancy with the exception of
currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in
situ" of the cervix or breast.
- Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.
- Known seropositive for or positive viral load for HIV or positive viral loads for
infectious hepatitis, type B (HBV) or C (HCV).
- Uncontrolled intercurrent active infection. Controlled infection on long term
suppressive or maintenance therapy is permissible.
- Use of live vaccines within four weeks of starting abatacept.