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

NCT ID: NCT01002742

Last Updated: 2023-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 236 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2013-06-30

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.

Detailed Description

Corticosteroids have been used as primary therapy for acute GVHD for many years. Historical published and unpublished data from Johns Hopkins, M. D. Anderson, University of Michigan and others defined an expected 35%-53% complete response (CR) at Day +28 of corticosteroid therapy for previously untreated patients with acute GVHD.

BMT CTN study 0302 (NCT00224874)was a randomized Phase II study evaluating etanercept, mycophenolate mofetil, denileukin diftitox or pentostatin in addition to corticosteroids. The results of that study suggested that mycophenolate mofetil produced the highest rates of CR at Day 28 and overall survival, supporting its evaluation in a Phase III study. Day 56 GVHD-free survival for the four treatment arms (all combining corticosteroids with one of the four study drugs) ranged from 39-71% across the four study arms.

Conditions

Graft-versus-Host Disease; Immune System Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Corticosteroids with placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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.

Mycophenolate Mofetil

Corticosteroids with Mycophenolate Mofetil

Group Type: EXPERIMENTAL

Mycophenolate Mofetil

Intervention Type: 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.

Interventions

Mycophenolate Mofetil

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Cellcept®; MMF; Inactive drug

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary Horowitz, MD

Role: STUDY_DIRECTOR

Center for International Blood and Marrow Transplant Research

Locations

City of Hope National Medical Center

Duarte, California, United States

University of California San Diego Medical Center

La Jolla, California, United States

Stanford Hospital and Clinics

Stanford, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

University of Florida College of Medicine

Gainesville, Florida, United States

BMT Program at Northside Hospital

Atlanta, Georgia, United States

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Indiana BMT at Beech Grove

Beech Grove, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Maryland Medical Systems

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

DFCI, Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute, Brigham & Women's Hospital

Boston, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University, Barnes Jewish Hospital

St Louis, Missouri, United States

Hackensack Univ. Medical Center

Hackensack, New Jersey, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College, NY Presbyterian Hospital

New York, New York, United States

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, United States

Levine Children's Hospital, Carolinas Medical Center

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Avera Hematology & Transplant Center

Sioux Falls, South Dakota, United States

Baylor University Medical Center

Dallas, Texas, United States

University of Texas, MD Anderson Cancer Research Center

Houston, Texas, United States

Texas Transplant Institute

San Antonio, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 25170121 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32081787 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

U01HL069294

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMT CTN 0802

Identifier Type: OTHER

Identifier Source: secondary_id

U01HL069294-06

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5U24CA076518

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMTCTN0802

Identifier Type: -

Identifier Source: org_study_id