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

• Status: Active, not recruiting
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: John Levine
• Collaborator: Biogen
• Treatments: Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Natalizumab; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone

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. 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