Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD

NCT ID: NCT02176031

Last Updated: 2020-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2019-02-28

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.

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Natalizumab

Natalizumab-

• (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion
• At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab.
• If participants have no response after one dose, they will be not be given a second dose.
• Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered.
• Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365.
• Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert

Group Type: EXPERIMENTAL

Natalizumab

Intervention Type: DRUG

Methylprednisolone

Intervention Type: DRUG

Interventions

Natalizumab

Intervention Type: DRUG

Methylprednisolone

Intervention Type: DRUG

Other Intervention Names

Tysabri®; Steroid

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Corey S. Cutler, MD, MPH

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Corey Cutler, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

14-140

Identifier Type: -

Identifier Source: org_study_id