Acute Graft-versus-Host Disease Treatment (BMT CTN 0802)

NCT01002742 | Completed Phase 3 Results DMC

• 5 other identifiers: BMTCTN0802U01HL069294BMT CTN 0802U01HL069294-065U24CA076518
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 36

Brief Summary

The study is a Phase III, randomized double blind, placebo controlled, and trial evaluating the addition of Mycophenolate mofetil (MMF) vs. placebo to systemic corticosteroids as initial therapy for acute Graft Vs Host Disease (GVHD). The primary endpoint will be GVHD free survival at Day 56 post randomization.

Conditions

Graft-versus-Host Disease; Immune System Disorders

Keywords

GVHD

Outcome Measures

Primary Outcomes (1)

• GVHD-free Survival

  Success is defined as alive and free of GVHD at day 56 after randomization, all others are considered to be a study failure.

  Day 56

Secondary Outcomes (14)

• Percentage of Surviving Participants With Complete Response (CR)

  Days 14, 28, and 56

• Incidence of GVHD Flares Requiring Increased Therapy

  Day 90

• Incidence of Discontinuation of Immune Suppression Without Flare

  Day 56, Day 180 and Day 360 post-treatment

• Cumulative Steroid Dose

  Days 28 and 56

• Incidence of Topical/Non-absorbable Therapy

  Day 56

Study Arms (2)

Placebo

EXPERIMENTAL

Corticosteroids with placebo

Drug: Placebo

Mycophenolate Mofetil

EXPERIMENTAL

Corticosteroids with Mycophenolate Mofetil

Drug: Mycophenolate Mofetil

Interventions

Mycophenolate Mofetil DRUG

Oral dosing should be delivered in 250 mg units. For those \< 40 kg, IV dosing should be within ± 10% of the exact dose. Intravenous doses are infused over a two-hour period. * Patients who weight \> 60 kg should receive MMF 1 gm PO/IV every 8 hours. * Patients who weight between 40-60 kg should receive 750 mg PO/IV every 8 hours. * Patients who weight \<40 kg should receive 20 mg/kg IV or PO every 8 hours.

Also known as: Cellcept®, MMF

Mycophenolate Mofetil

Placebo DRUG

Oral dosing should be delivered in 250 mg units blinded placebo. For those \< 40 kg, IV dosing should be within ± 10% of the exact dose. Intravenous doses are infused over a two-hour period. * Patients who weight \> 60 kg should receive placebo 1 gm PO/IV every 8 hours. * Patients who weight between 40-60 kg should receive 750 mg PO/IV every 8 hours. * Patients who weight \<40 kg should receive 20 mg/kg IV or PO every 8 hours.

Also known as: Inactive drug

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute GVHD developing after allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or cord blood. Recipients of non-myeloablative and myeloablative transplants are eligible.
• Acute GVHD after planned donor lymphocyte infusion or planned T cell add back are eligible.
• De novo acute GVHD requiring systemic therapy. GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis presenting in a context in which acute GVHD is likely to occur and where other etiologies such as drug rash, enteric infection, or hepatotoxic syndromes are unlikely or have been ruled out. Note that patients with stage I and II skin only (overall grade I) or isolated upper gastrointestinal (GI) involvement are eligible if the treating physician deems that systemic high-dose corticosteroid treatment is indicated.
• The patient must have had no previous systemic immune suppressive therapy for treatment of acute GVHD except for a maximum 72 hours of prior corticosteroid therapy at \>0.5mg/kg methylprednisolone or equivalent after the onset of acute GVHD.
• Clinical status at enrollment to allow tapering of steroids to not less than 0.25 mg/kg/day prednisone (0.2 mg/kg/day methylprednisolone) at Day 28 of therapy.
• Absolute neutrophil count (ANC) greater than 500/µL.
• Written informed consent and/or assent from patient, parent or guardian.
• Documentation that the assent document and education materials have been provided to, and reviewed with, patients between the ages of 7 and 17.
• Patients of all ages are eligible.
• Biopsy confirmation of GVHD is recommended, but not required. Enrollment should not be delayed for biopsy or pathology results unless these are to be used to decide about whether to treat for GVHD.

You may not qualify if:

• Patients receiving mycophenolate mofetil or mycophenolic acid (Myfortic) within seven days of screening for enrollment.
• Patients with uncontrolled infections will be excluded. If a bacterial or viral infection is present, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. If a fungal infection is present, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Relapsed/persistent malignancy requiring rapid immune suppression withdrawal.
• Patients with GVHD after an unplanned Donor Lymphocyte Infusion (DLI), i.e., DLI that was not part of their original transplant therapy plan, or DLI given for treatment of persistent or recurrent malignancy after transplantation.
• Patients unlikely to be available at the transplantation center on Day 28 and 56 of therapy.
• A clinical syndrome resembling de novo chronic GVHD developing at any time after allotransplantation.
• Patients receiving other drugs for the treatment of GVHD.
• Patients receiving methylprednisolone \> 0.5 mg/kg/day (or 0.6 mg/kg/day prednisone) within 7 days before the onset of acute GVHD. If steroid therapy has been administered for treatment of a non-GVHD related condition and tapered to ≤ 0.5 mg/kg/day methylprednisolone (0.6 mg/kg/day prednisone) for seven or more days before the onset of acute GVHD, the patient is eligible.
• Patients who are pregnant, breast feeding, or, if sexually active, unwilling to use effective birth control for the duration of the study. Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding, therefore breast feeding patients are not eligible.
• Adults unable to provide informed consent.
• Patients on dialysis.
• Patients with severe hepatic Veno-Occlusive Disease (VOD) or sinusoidal obstruction syndrome who in the judgement of the treating physician are not expected to have normalized bilirubin by Day 56 after enrollment.
• Patients with a history of intolerance/allergy to MMF.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (36)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California San Diego Medical Center

La Jolla, California, 92093, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

BMT Program at Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana BMT at Beech Grove

Beech Grove, Indiana, 46107, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Maryland Medical Systems

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

DFCI, Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute, Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University, Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Hackensack Univ. Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Weill Cornell Medical College, NY Presbyterian Hospital

New York, New York, 10065, United States

Location

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, 27599-7305, United States

Location

Levine Children's Hospital, Carolinas Medical Center

Charlotte, North Carolina, 28232, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Avera Hematology & Transplant Center

Sioux Falls, South Dakota, 57105, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas, MD Anderson Cancer Research Center

Houston, Texas, 77030, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Related Publications (2)

• Bolanos-Meade J, Logan BR, Alousi AM, Antin JH, Barowski K, Carter SL, Goldstein SC, Hexner EO, Horowitz MM, Lee SJ, Levine JE, MacMillan ML, Martin PJ, Mendizabal AM, Nakamura R, Pasquini MC, Weisdorf DJ, Westervelt P, Ho VT. Phase 3 clinical trial of steroids/mycophenolate mofetil vs steroids/placebo as therapy for acute GVHD: BMT CTN 0802. Blood. 2014 Nov 20;124(22):3221-7; quiz 3335. doi: 10.1182/blood-2014-06-577023. Epub 2014 Aug 28.

  PMID: 25170121 RESULT

• Shah O, Tamaresis JS, Kenyon LJ, Xu L, Zheng P, Gupta P, Rangarajan K, Lee S, Spellman S, Nikiforow S, Zehnder J, Meyer EH. Analysis of the Whole CDR3 T Cell Receptor Repertoire after Hematopoietic Stem Cell Transplantation in 2 Clinical Cohorts. Biol Blood Marrow Transplant. 2020 Jun;26(6):1050-1070. doi: 10.1016/j.bbmt.2020.01.020. Epub 2020 Feb 18.

  PMID: 32081787 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease; Immune System Diseases

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Results Point of Contact

• Title: Adam Mendizabal, PhD
• Organization: The Emmes Corporation

amendizabal@emmes.com

301-251-1161

Study Officials

• Mary Horowitz, MD

  Center for International Blood and Marrow Transplant Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2009
• First Posted: October 27, 2009
• Study Start: January 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: June 1, 2013
• Last Updated: January 4, 2023
• Results First Posted: May 27, 2016

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public

Locations

US (36)