Clinical trial NCT02176031: Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD
Official title: Phase II Trial of Natalizumab (Tysabri®) Plus Prednisone for Initial Therapy of Acute Graft Versus Host Disease (aGVHD) of the Gastrointestinal Tract
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Versus Host Disease
Keywords: Graft Versus Host Disease
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Biogen
First posted: 2014-06-26
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug Natalizumab in treating Acute Graft-Versus-Host Disease (GVHD) in the Gastrointestinal (GI) Tract.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: GVHD-free Survival Rate
timeFrame: Day 56
Secondary outcomes:
measure: Graft-verus-host Disease (GVHD) Response Rate
timeFrame: 28 Days, 56 Days
measure: GI aGVHD Response Rate
timeFrame: Day 28, Day 56
measure: Overall Survival (OS) Rate
timeFrame: 2 years
measure: Rate of GVHD Flares
timeFrame: by Day 28
measure: Percentage Steroid Dose Was Reduced at Day 28, 56, and 100 in Comparison to Steroid Dose at First Administration of Natalizumab.
timeFrame: Day 28, 56, and 100
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Corey Cutler, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: