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Natalizumab and Prednisone or Methylprednisolone in Treating Participants with High Risk Acute Graft-Versus-Host Disease

Trial Status: Active

This phase II trial studies how well natalizumab and prednisone or methylprednisolone work in treating participants with high risk acute graft-versus-host disease. Graft-versus-host disease is caused when cells from a donated stem cell graft attack the normal tissue of the transplant patient. Immunotherapy with monoclonal antibodies, such as natalizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Prednisone and methylprednisolone are steroids that helps suppress the immune system and reduce inflammation. It is not yet known how well natalizumab and prednisone or methylprednisolone work in treating participants with high risk acute graft-versus-host disease.

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Contact: Monzr M. Al Malki
Phone: 626-256-4673ext62405

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: ACTIVE
Contact: Amelia A. Langston
Phone: 404-778-4236

Illinois

Chicago
Northwestern University
Status: ACTIVE
Contact: Kehinde U.A. Adekola
Phone: 312-695-2597

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE
Contact: Sunil H. Abhyankar
Phone: 913-588-6030

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: ACTIVE
Contact: Yi-Bin A. Chen
Phone: 617-726-0187

Minnesota

Rochester
Mayo Clinic in Rochester
Status: ACTIVE
Contact: William Joseph Hogan
Phone: 507-284-2017

New York

New York
Icahn School of Medicine at Mount Sinai
Status: ACTIVE
Contact: John Eric Levine
Phone: 212-241-6021
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Doris Mariela Ponce
Phone: 212-639-4838
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE
Contact: Ran Reshef
Phone: 212-342-0530

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE
Contact: Yvonne Adeduni Efebera
Phone: 614-293-2268

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: ACTIVE
Contact: David L. Porter
Phone: 215-662-2862

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: ACTIVE
Contact: Carrie Lynn Kitko
Phone: 615-936-2088

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.

OUTLINE:

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

Lead Organization
Icahn School of Medicine at Mount Sinai

Principal Investigator
John Eric Levine

  • Primary ID 14-1413-3
  • Secondary IDs NCI-2018-00027, GCO 15-1624
  • Clinicaltrials.gov ID NCT02133924