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Graft vs Host DiseasePhase 2NCT00224874

Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302)

A Phase 2 study testing Etanercept, Mycophenolate Mofetil and Denileukin Diftitox in people with Graft vs Host Disease and Immune System Disorders, run by National Heart, Lung, and Blood Institute (NHLBI) at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The study is a randomized Phase II, four arm treatment trial. The primary purpose of the study is to define new agents with promising activity against acute graft-versus-host disease (GVHD) suitable for testing against corticosteroids alone in a subsequent Phase III trial. Read more about this study

Who is it for?
Ages 2 years and older
What is being tested?
Etanercept, Mycophenolate Mofetil and Denileukin Diftitox
Could I receive a placebo?
No, everyone receives an active treatment
How many people
180 participants
Where
19 sitesUnited States
Study dates
Sep 2005to Jun 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Prior allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells, or cord blood
  • De novo acute GVHD diagnosed within 48 hours prior to enrollment; biopsy confirmation of GVHD is strongly recommended but not required; enrollment should not be delayed awaiting biopsy or pathology results; the patient must have had no previous systemic immune suppressive therapy given for treatment of acute GVHD except for a maximum 48 hours of prior corticosteroid therapy (at least 1 mg/kg/day methylprednisolone)
  • Patients that have undergone a scheduled donor lymphocyte infusion (DLI) as part of their original transplant therapy plan
  • Absolute neutrophil count (ANC) greater than 500/µL
  • Clinical status at enrollment to allow tapering of steroids to not less than 1 mg/kg/day methylprednisolone (1.4 mg/kg/day prednisone) at Day 28 of therapy (e.g., persisting malignant disease suggesting the need for accelerated taper of immunosuppression)
  • Estimated creatinine clearance greater than 30 mL/minute
  • Assent and educational materials provided to, and reviewed with, patients under the age of 18

Who cannot join

  • ONTAK, pentostatin, or etanercept given within 7 days of enrollment
  • Active uncontrolled infection
  • Patients that have undergone an unscheduled DLI, or DLI that was not part of their original transplant therapy plan
  • If any prior steroid therapy (for indication other than GVHD), treatment at doses of at least 0.5 mg/kg/day methylprednisolone within 7 days prior to onset of GVHD
  • Patients unlikely to be available at the transplant center on Day 28 and 56 of therapy
  • A clinical syndrome resembling de novo chronic GVHD developing at any time after allotransplantation (see Chapter 2 of the BMT CTN Manual of Procedures for details of de novo chronic GVHD)
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  • Other investigational therapeutics for GVHD within 30 days, including agents used for GVHD prophylaxis
  • Patients who are pregnant, breast feeding, or if sexually active, unwilling to use effective birth control for the duration of the study
  • Adults unable to provide informed consent
  • Patients with a history of intolerance to any of the study drugs

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites
  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Johns Hopkins/SKCCC

    Baltimore, Maryland, 21231

  • DFCI/Brigham & Women's Hospital

    Boston, Massachusetts, 02114

  • University Hospitals of Cleveland/Case Western

    Cleveland, Ohio, 44106

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Duke University Medical Center (Peds)

    Durham, North Carolina, 27705

  • University of Florida College of Medicine (Shands)

    Gainesville, Florida, 32610

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • University of Texas/MD Anderson CRC

    Houston, Texas, 77030

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • University of Pennsylvania Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Oregon Health Sciences University

    Portland, Oregon, 97239

  • Texas Transplant Institute

    San Antonio, Texas, 78229

  • University of California

    San Diego, California, 92093

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Washington University/Barnes Jewish Hospital

    St Louis, Missouri, 63110

  • Stanford Hospital and Clinics

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Initial Systemic Treatment of Acute GVHD: A Phase II Randomized Trial Evaluating Etanercept, Mycophenolate Mofetil (MMF), Denileukin Diftitox (ONTAK), and Pentostatin in Combination With Corticosteroids (BMT CTN #0302)

The study is a randomized Phase II, four arm treatment trial. The primary purpose of the study is to define new agents with promising activity against acute graft-versus-host disease (GVHD) suitable for testing against corticosteroids alone in a subsequent Phase III trial.

Read the detailed description

BACKGROUND:

Acute graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell (HSC) transplantation. Acute GVHD produces significant morbidity and complicates patient management resulting in organ toxicity, frequent infections, malnutrition, and substantial delay in recovery from transplantation. Corticosteroids have been the primary therapy for acute GVHD for over three decades. Various additional immunosuppressive strategies have been tested as GVHD therapy but neither anti-thymocyte globulin (ATG), CD5-immunotoxins, IL-1 antagonists nor other agents have been demonstrably helpful in either control of GVHD symptoms or improvement in survival. Published response rates of complete response (CR) to acute GVHD therapy with corticosteroids range from 25-41%. These rates will be used as benchmarks for assessing efficacy of promising new agents. New immunosuppressive agents and strategies are required to improve the management of GVHD and decrease the toxicities of the immunosuppressive regimens.

DESIGN NARRATIVE:

In this trial, patients with newly diagnosed acute GVHD will be randomly assigned to receive corticosteroids plus one of four new agents (etanercept, MMF, denileukin diftitox [Ontak], and pentostatin). A control arm of only corticosteroids will not be employed. Each agent will be assessed for safety and efficacy (at least 35% complete remission [CR] rate at Day 28 of therapy can be expected from previously untreated patients).

Being tested
Etanercept, Mycophenolate Mofetil, Denileukin Diftitox, Pentostatin
Keywords
Acute Graft vs Host Disease, GVHD
Medical subject headings
Graft vs Host Disease, Immune System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EtanerceptDrug

    Also called ENBREL®

    Etanercept [25 mg subcutaneously twice weekly for up to 4 weeks; discontinue if in complete response by 4 weeks].

  • Mycophenolate MofetilDrug

    Also called CellCept®

    Mycophenolate mofetil (MMF) [20 mg/kg (maximum 1 gm) orally or intravenously twice daily; continue through prednisone taper, then taper MMF over 4 weeks].

  • Denileukin DiftitoxDrug

    Also called ONTAK®

    Denileukin Diftitox (ONTAK®) [9 mcg/kg intravenously Days 1, 3, 5, 15, 17, 19].

  • PentostatinDrug

    Also called Nipent®

    Pentostatin [1.5 mg/m2 daily for 3 days; Days 1-3 and repeat Days 15-17

Study groups in NCT00224874
Study groupRoleWhat they receive
EtanerceptExperimentalEnroll within 48 hours of new onset acute GVHD and randomize to Etanercept
Receives: Drug: Etanercept
Mycophenolate MofetilExperimentalEnroll within 48 hours of new onset acute GVHD and randomize to Mycophenolate Mofetil
Receives: Drug: Mycophenolate Mofetil
Denileukin DiftitoxExperimentalEnroll within 48 hours of new onset acute GVHD and randomize to Denileukin Diftitox
Receives: Drug: Denileukin Diftitox
PentostatinExperimentalEnroll within 48 hours of new onset acute GVHD and randomize to Pentostatin
Receives: Drug: Pentostatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Complete Response (CR) at Day 28 of Therapy

    Complete response at day 28 after randomization. CR was defined as resolution of all signs and symptoms of Graft-Versus-Host Disease (GVHD) in all evaluable organs in comparison to Day 1 scoring.

    Measured: Measured at Day 28

Secondary outcomes (8)
  1. Number of Partial Response (PR), Mixed Response (MR), and Progression

    Partial response, mixed response, and progression at Day 28 after randomization. Partial response was defined as improvement in one or more organs involved with Graft-Versus-Host Disease (GVHD) symptoms without progression in others. Mixed response was defined as improvement in one or more organs with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ. Progression was defined as deterioration in at least one organ without any improvement in others.

    Measured: Measured at Day 28

  2. Proportion of Treatment Failure

    Measured: Measured at Day 56

  3. Number of Patients With Acute Graft-versus-host Disease (GVHD) Flares at Day 90

    Flares were defined as any increase in symptoms of or therapy for acute GVHD after an initial response (i.e., progression from an earlier CR or PR).

    Measured: Measured at Day 90

  4. Number of Patients Discontinuing Immune Suppression Without Flare

    Immunosuppression discontinuation was defined as the discontinuation of corticosteroids and all additional immunosuppressives, except cyclosporine or tacrolimus, for treatment of acute GVHD without subsequent flare by Day 90 post-initiation of therapy and later by discontinuation of all immunosuppressive medications, including cyclosporine or tacrolimus.

    Measured: Measured at Days 90, 180, and 270 post-treatment

  5. Number of Patients With Chronic Graft-versus-host Disease (GVHD)

    Number of patients with limited and extensive chronic GVHD at 9 months

    Measured: Measured at 9 months

  6. Number of Patients Surviving at 6 and 9 Months Post Randomization

    Measured: Measured at 6 and 9 months

  7. Cumulative Incidence of Systemic Infections

    Measured: Measured at Day 270

  8. Incidence of Epstein-Barr Virus (EBV)-Associated Lymphoma

    Measured: Measured at 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2005 (estimated)
  2. Study startSep 2005
  3. Primary completionJan 2009
  4. Study completionJun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
180 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00224874
Sponsor's protocol ID
BMTCTN0302
Other IDs
BMT CTN 0302, U01HL069294-05, 285
Status last verified
Aug 2017
First submitted
21 Sep 2005
Last updated
1 Nov 2021
Data monitoring committee
Yes
Individual data sharing
Yes: Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).

Publications

  • Alousi AM, Weisdorf DJ, Logan BR, Bolanos-Meade J, Carter S, Difronzo N, Pasquini M, Goldstein SC, Ho VT, Hayes-Lattin B, Wingard JR, Horowitz MM, Levine JE; Blood and Marrow Transplant Clinical Trials Network. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network. Blood. 2009 Jul 16;114(3):511-7. doi: 10.1182/blood-2009-03-212290. Epub 2009 May 14.

    PubMed 19443659
  • Jacobson PA, Huang J, Wu J, Kim M, Logan B, Alousi A, Grimley M, Bolanos-Meade J, Ho V, Levine JE, Weisdorf D. Mycophenolate pharmacokinetics and association with response to acute graft-versus-host disease treatment from the Blood and Marrow Transplant Clinical Trials Network. Biol Blood Marrow Transplant. 2010 Mar;16(3):421-9. doi: 10.1016/j.bbmt.2009.11.010.

    PubMed 19925875
  • Levine JE, Logan B, Wu J, Alousi AM, Ho V, Bolanos-Meade J, Weisdorf D; Blood and Marrow Transplant Clinical Trials Network. Graft-versus-host disease treatment: predictors of survival. Biol Blood Marrow Transplant. 2010 Dec;16(12):1693-9. doi: 10.1016/j.bbmt.2010.05.019. Epub 2010 Jun 9.

    PubMed 20541024
  • Levine JE, Logan BR, Wu J, Alousi AM, Bolanos-Meade J, Ferrara JL, Ho VT, Weisdorf DJ, Paczesny S. Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study. Blood. 2012 Apr 19;119(16):3854-60. doi: 10.1182/blood-2012-01-403063. Epub 2012 Mar 1.

    PubMed 22383800

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Etanercept, Mycophenolate Mofetil and Denileukin Diftitox in people with Graft vs Host Disease and Immune System Disorders, run by National Heart, Lung, and Blood Institute (NHLBI) at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Apr 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Complete Response (CR) at Day 28 of Therapy (time frame: Measured at Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00224874, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.

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