Natalizumab and Prednisone or Methylprednisolone in Treating Participants with High Risk Acute Graft-Versus-Host Disease
- New onset acute GVHD Ann Arbor score 2 or 3 following allogeneic bone marrow transplantation (BMT); 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 (or IV methylprednisolone) =< 2 mg/kg/day; topical skin steroid treatment, non-absorbable oral steroid treatment for gastrointestinal (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
- Direct bilirubin must be < 2 mg/dL unless the elevation is known to be due to Gilbert's syndrome or acute GVHD (aGVHD) within 3 days of enrollment
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) 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 or legal representative
- 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 initiation of systemic steroid treatment for acute GVHD are not permitted to participate
- Patients with malignancy that is suspected or proven to have progressed, relapsed, or be persistent since progressive, relapsed or persistent malignancy documented since BMT
- Uncontrolled active infection
- Patients with chronic GVHD only; patients diagnosed with overlap syndrome are still eligible
- History of or current diagnosis of progressive multifocal leukoencephalopathy (PML)
- 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- principal investigator (PI)
- History of allergic reaction to natalizumab
I. To improve day 28 graft versus host disease (GVHD) complete response rate for Ann Arbor score 2 and 3 GVHD patients from the historical rate of 42.5% to 57.5% by treatment with natalizumab and high dose prednisone (or methylprednisolone) (2 mg/kg).
I. To decrease 6-month non-relapse mortality (NRM) from the historical rate of 32% to 22% in patients treated on this clinical trial.
II. To determine the overall survival and NRM rates at 1 year and the cumulative incidence of treatment-refractory GVHD (defined as no improvement or worsening in any target organ by day 28 of treatment or who receive additional immunosuppression prior to day 28), the day 28 overall response rate (CR + PR), time to discontinuation of steroid therapy, number of lines of GVHD therapy, and cumulative incidence of chronic GVHD in patients treated on this clinical trial.
III. To determine the cumulative incidence of 6 month and 1 year relapse and the incidence of serious infections by 6 months in patients treated on this clinical trial.
IV. To assess the safety of natalizumab for the treatment of high risk GVHD.
V. To assess the improvement in day 28 GVHD complete response rate for Ann Arbor score 2 and 3 patients separately in order to evaluate any differences in response to the treatment between two groups.
Participants receive prednisone orally (PO) daily or methylprednisolone intravenously (IV) on days 0-2 followed by a taper protocol per local institution practices, and natalizumab IV over 1 hour on days 0 and 14.
After completion of study treatment, participants are followed up weekly for the first 4 weeks, every other week for the next 6 weeks, and then every 3 months up to 1 year.
Trial Phase Phase II
Trial Type Treatment
Icahn School of Medicine at Mount Sinai
John Eric Levine
- Primary ID 14-1413-3
- Secondary IDs NCI-2018-00027, GCO 15-1624
- Clinicaltrials.gov ID NCT02133924