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

NCT01954979 | Completed Phase 1 DMC

• 1 other identifier: 13-358
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Chronic Graft Versus Host Disease

Keywords

Graft versus Host Disease; ABATACEPT

Outcome Measures

Primary Outcomes (1)

• Determination of the Maximum Tolerated Dose (among two dose levels) and toxicity profile of a 141 day/6 dose course of abatacept in patients with steroid refractory cGVHD.

  Determination of the Maximum Tolerated Dose (among two dose levels) and toxicity profile of a 141 day/6 dose course of abatacept in patients with steroid refractory cGVHD.

  2 Years

Secondary Outcomes (2)

• Determination of the efficacy (in terms of cGVHD symptoms, score and steroid dose) of a 141 day/6 dose course of abatacept in patients with steroid refractory cGVHD

  2 Years

• Examination of the immunologic effects associated with the administration of abatacept in patients with steroid refractory cGVHD.

  2 Years

Study Arms (1)

Abatacept

EXPERIMENTAL

Abatacept will be administered for a total of 6 doses. Doses 1-3 will be administered at two week intervals (+/-2 days). One month following Dose 3, abatacept will be administered, and given at four-week intervals (+/-2 days) for three doses (Doses 4-6.) Patients will be followed for toxicity for 28 days following last dose of Abatacept. Patients will then be seen monthly for six months.

Drug: Abatacept

Interventions

Abatacept DRUG

The study will follow a standard 3+3 design with two escalating doses of abatacept to determine the maximum tolerated dose (MTD): 3 mg/kg (dose level 1) and 10 mg/kg (dose level 2). Dose-limiting toxicities (DLTs) are defined as any Grade 3 or 4 toxicities judged to be probably or definitely related to abatacept.

Abatacept

Eligibility Criteria

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

You may qualify if:

• 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 lymphocyte infusion.
• Participants must have cGVHD (as defined by the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease)
• 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 mIU/mL.
• Women who are taking hormone replacement therapy (HRT).
• The following women are WOCBP:

You may not qualify if:

• 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 with abatacept.
• 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 abatacept.
• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Bristol-Myers Squibb: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (2)

• Koshy AG, Kim HT, Liegel J, Arnason J, Ho VT, Antin JH, Joyce R, Cutler C, Gooptu M, Nikiforow S, Logan EK, Elavalakanar P, Narcis M, Stroopinsky D, Avigan ZM, Boussi L, Stephenson S, El Banna H, Bindal P, Cheloni G, Avigan DE, Soiffer RJ, Rosenblatt J. Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Blood. 2023 Jun 15;141(24):2932-2943. doi: 10.1182/blood.2022019107.

  PMID: 36862975 DERIVED

• Nahas MR, Soiffer RJ, Kim HT, Alyea EP 3rd, Arnason J, Joyce R, Antin JH, Ho VT, Stroopinsky D, Li S, Levine JD, McMasters M, Jain S, Hamdan A, Tzachanis D, Bryant MP, Logan EK, Bazemore J, Stewart J, Joyce A, Stephenson S, Washington A, Cole L, Pyzer A, Leaf RK, Avigan DE, Rosenblatt J. Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Blood. 2018 Jun 21;131(25):2836-2845. doi: 10.1182/blood-2017-05-780239. Epub 2018 Mar 16.

  PMID: 29549175 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Graft vs Host Disease

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Jacalyn Rosenblatt, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 27, 2013
• First Posted: October 7, 2013
• Study Start: March 27, 2014
• Primary Completion: June 1, 2023
• Study Completion: January 16, 2024
• Last Updated: January 18, 2024

Record last verified: 2024-01

Locations

US (2)