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

  • STATUS
    Recruiting
  • End date
    Apr 26, 2022
  • participants needed
    90
  • sponsor
    John Levine
Updated on 26 January 2021
cancer
corticosteroids
sirolimus
hematologic malignancy
lymphoma
bone marrow transplant
calcineurin inhibitor
direct bilirubin
steroid therapy
corticosteroid therapy
leukemia
natalizumab

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.

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 starting systemic steroid treatment for 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.

Details
Condition Acute Graft-versus-Host Disease, Acute GVHD, Acute Graft Versus Host Disease
Treatment natalizumab, Steroids
Clinical Study IdentifierNCT02133924
SponsorJohn Levine
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have Acute Graft Versus Host Disease?
Do you have any of these conditions: Acute GVHD or Acute Graft Versus Host Disease or Acute Graft-versus-Host Disease?
Do you have any of these conditions: Acute Graft Versus Host Disease or Acute GVHD or Acute Graft-versus-Host Disease?
Do you have any of these conditions: Acute Graft-versus-Host Disease or Acute GVHD or Acute Graft Versus Host Disease?
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. Patients with prior or existing diagnosis of GVHD without any treatment are eligible. Patients given only topical corticosteroids for skin GVHD are 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 3 days of prednisone 2 mg/kg/day (or IV methylprednisolone). Topical skin steroid treatment, non-absorbable oral steroid treatment for GI GVHD, and resumption of GVHD prophylaxis agents (e.g., calcineurin inhibitors) are permissible. Patients enrolled in BMT CTN 1501 who randomized to sirolimus are also eligible
Age 18 years or older
Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome or aGVHD within 3 days of enrollment
ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days of enrollment, unless the elevation is due to liver GVHD
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
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 3 days of systemic steroid treatment for acute GVHD are not permitted to participate

Exclusion Criteria

Progressive or relapsed malignancy since BMT
Uncontrolled active infection
Patients with chronic GVHD only. Patient with overlap syndrome are eligible
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
Steroid therapy for indications other than GVHD at doses >0.5 mg/kg/d of methylprednisolone or equivalent within 7 days prior to initiation of GVHD treatment
Patients on dialysis
Patients requiring ventilator support
Investigational agent within 30 days of enrollment without approval from the Sponsor-Investigator
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