Trial record 6 of 20 for:    Tysabri | Open Studies

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2015 by Icahn School of Medicine at Mount Sinai
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
John Levine, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:
NCT02133924
First received: May 6, 2014
Last updated: September 15, 2015
Last verified: September 2015
  Purpose

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.


Condition Intervention Phase
Acute Graft Versus Host Disease
Drug: natalizumab
Drug: steroids
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PHASE II Multicenter Study Of Natalizumab Plus Standard Steroid Treatment For High Risk Acute Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by Icahn School of Medicine at Mount Sinai:

Primary Outcome Measures:
  • Complete Response (CR) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    The primary endpoint for this clinical study is the proportion of complete response, CR (that is, the percent of patients with skin, liver, and GI GVHD - all stage 0) at day 28 of study treatment.


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Non-Relapse Mortality (NRM) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Cumulative incidence of Non-Relapse Mortality (NRM)at 6 months and 1 year

  • incidence of treatment-refractory GVHD [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Cumulative incidence of treatment-refractory GVHD (defined as absence of CR or PR on day 28 of treatment or who receive additional immunosuppression prior to day 28)

  • Time to discontinuation of steroid therapy [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Number of additional GVHD therapies [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Number of additional GVHD therapies (defined as the initiation of a new acute GVHD therapy, regardless of duration)

  • Number of serious infections [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Number of serious infections (defined as score 3 by the Blood and Marrow Transplant Clinical Trials Network)

  • Overall response rate (CR + PR) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Overall response rate (CR + PR) at day 28. Partial Response (PR) is defined as improvement in one or more organs involved with GVHD symptoms without progression in others. For a response to be scored as PR on day 28, the patient must be in PR on day 28 and have had no intervening non-study therapy for acute GVHD.


Estimated Enrollment: 90
Study Start Date: November 2015
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Natalizumab with steroids

For subjects whose GVHD assay is Ann Arbor score 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) and natalizumab.

Protocol treatment must start within 3 days of the subject's diagnosis of acute GVHD.

Drug: natalizumab
Natalizumab 300mg (or 4.3 mg/kg for subjects <18y or <50kg) on days 0 and 14.
Other Name: Tysabri
Drug: steroids
Prednisone 2mg/kg/d (or methyl-prednisolone IV equivalent)
Other Names:
  • Prednisone
  • methylprednisolone equivalent IV

Detailed Description:

The only proven effective treatment for patients with acute graft vs host disease is steroids. Patients not responding 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 at the earliest stages of clinical symptoms, but, by using a proprietary method developed at the University of Michigan and the Icahn School of Medicine at Mount Sinai, are predicted to be at high risk for not responding to steroid therapy, the standard of care.

Investigators at Mount Sinai have developed a research method believed that it might make it possible to predict who is at high risk for not responding to steroids. This method, called Ann Arbor GVHD scoring, uses the levels of naturally occurring chemicals in the blood (called biomarkers) to determine a patient's GVHD score(1, 2, or 3).

A hypothesis is that most patients with Ann Arbor score 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 with Ann Arbor score 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 as Ann Arbor score 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 with disease that has not responded to the standard treatment, or 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

Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • New onset high risk acute GVHD (Ann Arbor score 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 ≤2 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02133924

Contacts
Contact: John E Levine, MD 212-241-6021 john.levine@mssm.edu
Contact: James Ferrara, MD 212-824-9365 james.ferrara@mssm.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Yi-Bin Chen, MD    617-724-1124    ychen6@partners.org   
Principal Investigator: Yi-Bin Chen, MD         
United States, Michigan
University of Michigan Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Steven Goldstein, MD    734-936-8456    stevengo@med.umich.edu   
Principal Investigator: Steven Goldstein, MD         
United States, Minnesota
Mayo Clinical Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Mark Litzow, MD    507-284-5362    litzow.mark@mayo.edu   
Principal Investigator: Mark Litzow, MD         
United States, New York
Mount Sinai Health System Not yet recruiting
New York, New York, United States, 10029
Contact: John E Levine, MD    212-241-6021    john.levine@mssm.edu   
Contact: Anne Renteria, MD    212-241-6021    anne.renteria@mssm.edu   
Principal Investigator: Anne Renteria, MD         
United States, Ohio
Ohio State University Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Steven Devine, MD    614-293-5655    steven.devine@osumc.edu   
Principal Investigator: Steven Devine, MD         
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: David Porter, MD    215-662-2862    david.porter@uphs.upenn.edu   
Principal Investigator: David Porter, MD         
United States, Tennessee
Vanderbilt University Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Madan Jagasia, MD    615-343-5374    madan.jagasia@vanderbilt.edu   
Principal Investigator: Madan Jagasia, MD         
Sponsors and Collaborators
John Levine
Biogen
Investigators
Study Chair: John E Levine, MD Ichan School of Medicine at Mount Sinai
  More Information

Responsible Party: John Levine, Professor of Pediatrics and Communicable Diseases, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT02133924     History of Changes
Other Study ID Numbers: UMCC 2014.051 
Study First Received: May 6, 2014
Last Updated: September 15, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Icahn School of Medicine at Mount Sinai:
Graft vs Host Disease
Graft vs Host Reaction
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
adverse effects

Additional relevant MeSH terms:
Natalizumab
Graft vs Host Disease
Immune System Diseases
Prednisolone acetate
Methylprednisolone acetate
Prednisone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 26, 2016