Phase 2
N=180
Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302)
Graft vs Host Disease · Immune System Disorders
Bottom Line
View on ClinicalTrials.gov: NCT00224874 ↗Enrolled (actual)
180
Serious AEs
8.3%
Results posted
Apr 2010
Primary outcome: Primary: Number of Complete Response (CR) at Day 28 of Therapy — 12; 27; 25; 16 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Etanercept (Drug); Mycophenolate Mofetil (Drug); Denileukin Diftitox (Drug); Pentostatin (Drug)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- National Heart, Lung, and Blood Institute (NHLBI)
- Primary completion
- Jan 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Complete Response (CR) at Day 28 of Therapy |
12; 27; 25; 16 | — |
| SECONDARY Number of Partial Response (PR), Mixed Response (MR), and Progression |
10; 8; 3; 10; 3; 4 | — |
| SECONDARY Proportion of Treatment Failure |
24; 9; 26; 29 | — |
| SECONDARY Number of Patients With Acute Graft-versus-host Disease (GVHD) Flares at Day 90 |
16; 12; 15; 15 | — |
| SECONDARY Number of Patients Discontinuing Immune Suppression Without Flare |
7; 4; 5; 2; 12; 13 | — |
| SECONDARY Number of Patients With Chronic Graft-versus-host Disease (GVHD) |
11; 19; 15; 12 | — |
| SECONDARY Number of Patients Surviving at 6 and 9 Months Post Randomization |
26; 32; 28; 24; 22; 29 | — |
| SECONDARY Cumulative Incidence of Systemic Infections |
47; 44; 62; 57 | — |
| SECONDARY Incidence of Epstein-Barr Virus (EBV)-Associated Lymphoma |
— | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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)
- 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
Data sourced from ClinicalTrials.gov (NCT00224874). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.