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

NCT02176031 | Completed Phase 2 Results DMC

• 1 other identifier: 14-140
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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.

Conditions

Graft Versus Host Disease

Keywords

Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• GVHD-free Survival Rate

  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 Outcomes (5)

• Graft-verus-host Disease (GVHD) Response Rate

  28 Days, 56 Days

• GI aGVHD Response Rate

  Day 28, Day 56

• Overall Survival (OS) Rate

  2 years

• Rate of GVHD Flares

  by Day 28

• Percentage Steroid Dose Was Reduced at Day 28, 56, and 100 in Comparison to Steroid Dose at First Administration of Natalizumab.

  Day 28, 56, and 100

Study Arms (1)

Natalizumab

EXPERIMENTAL

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

Drug: Natalizumab; Drug: Methylprednisolone

Interventions

Natalizumab DRUG

Also known as: Tysabri®

Natalizumab

Methylprednisolone DRUG

Also known as: Steroid

Natalizumab

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Biogen: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Natalizumab; Methylprednisolone; Steroids

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Corey Cutler
• Organization: Dana-Farber Cancer Institute

CSCUTLER@PARTNERS.ORG

617-632-3470

Study Officials

• Corey Cutler, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: June 25, 2014
• First Posted: June 26, 2014
• Study Start: January 1, 2015
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: April 17, 2020
• Results First Posted: April 17, 2020

Record last verified: 2020-04

Locations

US (2)