- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02176031
Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD
Phase II Trial of Natalizumab (Tysabri®) Plus Prednisone for Initial Therapy of Acute Graft Versus Host Disease (aGVHD) of the Gastrointestinal Tract
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Natalizumab is a drug that was initially discovered as a treatment for autoimmune conditions. Natalizumab has been approved for use in patients with Multiple Sclerosis and Crohn's disease. In these diseases, the drug works to inhibit dysfunctional immune cells that are responsible for the symptoms seen in these diseases. Acute graft versus host disease is caused by a similar dysfunction of immune cells; Natalizumab is thought to inhibit these immune cells, similarly to how it does in Multiple Sclerosis and Crohn's disease. In this research study,the investigators are looking to see whether Natalizumab provides additional benefit to patients receiving standard treatment for acute graft versus host disease of the gastrointestinal tract.
Participants who fulfill eligibility criteria will be entered into the trial to receive Natalizumab.
- Participant will receive a dose of the natalizumab through intravenous infusion. Participants may receive a second dose at Day 28 if they experience a partial response or very good partial response.
- Scheduled Physical Examination at screening, during the week of first dose and at 28 days, 56 days, 100 days, 180 days and one year.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
-
Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- Participants must have acute Graft-Versus-Host Disease (GVHD) of the lower gastrointestinal tract as defined by the clinical impression of the treating physician, requiring systemic treatment. Minimum criteria for GI GVHD includes diarrhea of greater than 500 mL/day. Biopsy of the GI tract is required for study entry and must confirm the diagnosis of acute GVHD. Stool samples to rule out infectious causes of diarrhea, including norovirus, Clostridium difficile and other clinically indicated infections must also be negative. Eligibility includes:
- Acute GVHD developing after allogeneic hematopoietic stem cell transplantation (HSCT) using bone marrow, peripheral blood stem cells, or umbilical cord blood. Recipients of non-myeloablative, reduced intensity and myeloablative transplants are eligible.
- Patients who develop acute GVHD after donor lymphocyte infusion (DLI) are eligible.
- There is no specified time window after day 0 of transplant as acute GVHD is only defined by clinical manifestations.
- Patients must have experienced neutrophil engraftment after HSCT as defined by absolute neutrophil counts ≥ 500 / µL × 3 consecutive measurements. Absolute neutrophil count (ANC) should be calculated using the standard formula (Neut + Bands)(WBC × 101).
- The presence of hepatic, upper GI and/or cutaneous acute GVHD is permitted.
- Steroids can be started up to 7 days prior to the administration of natalizumab.
- Age ≥ 18
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
- Patients with the entity of Acute/Chronic GVHD overlap syndromes.
- Requiring mechanical ventilation
- Vasopressor requirement
- Concurrent hepatic veno-occlusive disease (VOD) based on clinical examination
- Karnofsky performance status < 30
- Participants may not be receiving any other study agents for at least 7 days prior to enrollment
- Prior use of natalizumab for any reason is not allowed
- Pregnant women are excluded from this study because of the potential teratogenic effects of natalizumab. Because natalizumab enters breast milk, and the effect is unknown in infants, breastfeeding should be discontinued if the mother is treated with natalizumab.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Natalizumab
Natalizumab-
|
Other Names:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
GVHD-free Survival Rate
Time Frame: Day 56
|
Graft-versus-host disease (GVHD) free survival is defined as achieving complete response without death or relapse or requiring secondary immunosuppressive therapy .
Proportions are reported descriptively.
GVHD-free survival was assessed using the Kaplan-Meier method.
|
Day 56
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Graft-verus-host Disease (GVHD) Response Rate
Time Frame: 28 Days, 56 Days
|
|
28 Days, 56 Days
|
GI aGVHD Response Rate
Time Frame: Day 28, Day 56
|
Gastrointestinal (GI) acute graft-versus-host disease (GVHD) Response is defined by complete response, very good partial response, or partial response in signs and symptoms of GI aGVHD.
|
Day 28, Day 56
|
Overall Survival (OS) Rate
Time Frame: 2 years
|
Overall survival (OS) is defined from the date of natalizumab infusion to death or censored at last clinical evaluation.
OS was estimated using the Kaplan-Meier method.
|
2 years
|
Rate of GVHD Flares
Time Frame: by Day 28
|
Number of subjects who experienced graft-versus-host disease (GVHD) flares requiring therapy after initial complete response (CR) or partial response (PR) by day 28 after the first dose of Natalizumab.
|
by Day 28
|
Percentage Steroid Dose Was Reduced at Day 28, 56, and 100 in Comparison to Steroid Dose at First Administration of Natalizumab.
Time Frame: Day 28, 56, and 100
|
Median percentage steroid dose was reduced at Day 28, Day 56, and Day 100 in comparison to steroid dose at first administration of Natalizumab.
|
Day 28, 56, and 100
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Corey Cutler, MD, MPH, Dana-Farber Cancer Institute
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Graft vs Host Disease
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Prednisolone
- Methylprednisolone Acetate
- Methylprednisolone
- Methylprednisolone Hemisuccinate
- Prednisolone acetate
- Prednisolone hemisuccinate
- Prednisolone phosphate
- Natalizumab
Other Study ID Numbers
- 14-140
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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