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Multicenter Study Of Natalizumab Plus Standard Steroid Treatment For High Risk Acute Graft-Versus-Host Disease

Information source: University of Michigan Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Graft Versus Host Disease

Intervention: natalizumab (Drug); steroids (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: University of Michigan Cancer Center

Official(s) and/or principal investigator(s):
John E Levine, MD, Study Chair, Affiliation: University of Michigan

Overall contact:
John E Levine, MD, Phone: (734) 936-8456, Email: jelevine@med.umich.edu

Summary

This research trial is designed to study the safety and effectiveness of combining the study drug, Natalizumab (Tysabri«) with the standard treatment, the use of steroids, as a new treatment for acute graft versus host disease (acute GVHD). GVHD is the most common serious complication, after bone marrow transplant. GVHD occurs when the donor cells (the graft), treat the recipient's body as "foreign" and attack the cells in the recipient's body. During this immune system response, donor cells damage body tissues, such as the skin, liver, stomach, and/or intestines. Acute GVHD can be severe and if severe, potentially fatal to the transplant recipient. Acute GVHD usually happens within the first several months after transplant. The goal of this research is to develop a safer and more effective treatment for acute GVHD, and particularly for acute GVHD that affects the gastrointestinal (or GI) tract, with the ultimate goal being safer and more effective transplant therapies for blood cancers such as leukemia, lymphoma, and multiple myeloma.

Clinical Details

Official title: PHASE II Multicenter Study Of Natalizumab Plus Standard Steroid Treatment For High Risk Acute Graft-Versus-Host Disease

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Complete Response (CR)

Secondary outcome:

Overall survival (OS)

Non-Relapse Mortality (NRM)

incidence of treatment-refractory GVHD

Time to discontinuation of steroid therapy

Number of additional GVHD therapies

Number of serious infections

Overall response rate (CR + PR)

Detailed description: The only proven effective treatment for patients with acute graft vs host disease is steroids. Patients who do not respond to steroid treatment are at high risk for death. Unfortunately, based on the early symptoms, it is not possible to tell whether a patient will respond to steroids, when GVHD is diagnosed and treatment with steroids, such as prednisone, is started. This research trial is designed to study the safety and effectiveness of combining the study drug, Natalizumab (Tysabri®) with the use of steroids to treat acute GVHD in patients who are at the earliest stages of their clinical symptoms, but who, by using a proprietary method developed at the University of Michigan, are predicted to be at high risk for not responding to steroid therapy, the standard of care. Investigators at the University of Michigan have developed a research method, they believe might make it possible to predict who is at high risk for not responding to steroids. This method, called Ann Arbor GVHD grading, uses the levels of naturally occurring chemicals in the blood (called biomarkers) to determine a patient's GVHD grade (1, 2, or 3). A hypothesis is that most patients with Ann Arbor grade 3 GVHD, will not respond well to steroid treatment. The investigators research shows that almost half of the patients with Ann Arbor grade 3 GVHD, will die within 6 months of their GVHD diagnosis. Most of the deaths are due to intestinal GVHD, which sometimes does not develop, until after standard steroid treatment has already begun. Only patients who have Ann Arbor grade 3 GVHD, will be eligible for this study treatment. It is important to understand that Ann Arbor GVHD grading is not approved for clinical use. It can only be used as a test for research purposes. In this study, patients must have their blood tested to determine, if they qualify asre Ann Arbor grade 3 GVHD, and must start the study treatment within 3 days of their clinical diagnosis of acute GVHD. The study will test whether the investigators can improve steroid response and prevent death from GVHD with the combination therapy, by blocking the donor cells from getting to the intestine and causing damage. Natalizumab (Tysabri®) is a drug that works by blocking the signals that cause immune cells like donor cells, to travel to organs like the intestine or brain. Natalizumab is FDA-approved in adults, to treat Crohn's disease, a chronic condition where immune cells cause damage to the digestive system (such as the stomach, intestines). It is also used to treat multiple sclerosis where immune cells cause damage to the nervous system in the brain. Its intended use is for patients whose disease has not responded to the standard treatment, or who cannot tolerate the side effects from standard treatments. Natalizumab has never been used for treating GVHD. It is an experimental drug for this study, because the investigators are investigating a new use for the drug, as a GVHD treatment, and also because it has not been studied in pediatric patients (patients under the age of 18), even for its approved uses.

Eligibility

Minimum age: 12 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- New onset high risk acute GVHD (Ann Arbor grade 3 as defined in Appendix C of the

protocol) following allogeneic bone marrow transplantation. Any clinical severity (Glucksberg grade I-IV) is eligible.

- Any donor type (e. g., related, unrelated) or stem cell source (bone marrow,

peripheral blood, cord blood). Recipients of non-myeloablative and myeloablative transplants are eligible.

- No prior systemic treatment for acute GVHD except for a maximum of 72 hours of

prednisone ÔëĄ2 mg/kg/day (or IV methylprednisolone equivalent). Topical skin steroid treatment is permissible. Non-absorbable oral steroid treatment for GI GVHD is prohibited.

- Age 12 years or older.

- If the patient is a woman of child-bearing potential, the patient and their sexual

partner must agree to practice effective contraception.

- Written informed consent from patient, parent, or guardian.

- Written assent from patients age 12 to 17 years.

- Biopsy of acute GVHD target organ is strongly recommended, but not required.

Enrollment should not be delayed for biopsy or pathology results. Patients who do not enroll within 72 hours of new onset acute GVHD are not permitted to participate. Exclusion Criteria:

- Progressive or relapsed malignancy

- Uncontrolled active infection

- Patients with chronic GVHD

- Known seropositivity for JC virus

- History of Progressive Multifocal Leukoencephalopathy (PML)

- Known hypersensitivity to natalizumab

- Pregnant or nursing (lactating) women

- Use of other drugs for the treatment of acute GVHD

- Patients on dialysis

- Patients requiring ventilator support

- Investigational agent within 30 days of enrollment without approval from the

Sponsor-Investigator

Locations and Contacts

John E Levine, MD, Phone: (734) 936-8456, Email: jelevine@med.umich.edu

University of Michigan, Ann Arbor, Michigan 48109, United States; Not yet recruiting
John E Levine, MD, Phone: 734-936-8456, Email: jelevine@med.umich.edu
James Ferrara, MD, Phone: (734) 615-1340, Email: ferrara@med.umich.edu
John E Levine, MD, Principal Investigator
James Ferrara, MD, Sub-Investigator
Thomas Braun, Ph.D, Sub-Investigator

Mayo Clinic, Rochester, Minnesota 55905, United States; Not yet recruiting
Mark Litzow, MD, Phone: 507-284-5362, Email: litzow.mark@mayo.edu
Mark Litzow, MD, Principal Investigator

Ohio State University, Columbus, Ohio 43210, United States; Not yet recruiting
Steven Devine, MD, Phone: 614-293-5655, Email: steven.devine@osumc.edu
Steven Devine, MD, Principal Investigator

University of Pennsylvania, Abramson Cancer Center, Philadelphia, Pennsylvania 19104, United States; Not yet recruiting
David Porter, MD, Phone: 215-662-2862, Email: david.porter@uphs.upenn.edu
David Porter, MD, Principal Investigator

Additional Information

Starting date: June 2015
Last updated: May 18, 2015

Page last updated: August 23, 2015

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