Graft-Versus-Host Disease (GVHD) Acute on Chronic Clinical Trial
Official title:
Treatment of Steroid Non-responsive Acute GVHD With Alpha 1 Antitrypsin (AAT). A Phase I/II Study
| Verified date | October 2018 |
| Source | Fred Hutchinson Cancer Research Center |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This phase I/II trial evaluates the efficacy and adverse effects of alpha 1 anti-trypsin (AAT) for the treatment of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation.
| Status | Completed |
| Enrollment | 20 |
| Est. completion date | January 15, 2017 |
| Est. primary completion date | January 15, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Patients transplanted from related or unrelated, human leukocyte antigen (HLA) matched or mismatched donors - Patients transplanted with hematopoietic stem cells from any source - Patients receiving calcineurin inhibitors as part of graft versus host disease (GVHD) prophylaxis - Patients with acute GVHD grades II-IV developing despite GVHD prophylaxis - Patients who have not shown a satisfactory response to methylprednisolone-equivalent doses at 2 mg/kg/day, based on adjusted body weight - Signed and dated informed consent Exclusion Criteria: - Patients who have received any systemic agents in addition to steroids for treatment of GVHD - Patients unable to give informed consent - Patients with manifestations of classic chronic GVHD - Patients with evidence of recurrent malignancy - Patients with acute/chronic GVHD overlap syndrome - Patients whose GVHD developed after donor lymphocyte infusion (DLI) - Patients with severe organ dysfunction, defined as - On dialysis - Requiring oxygen (O2) at more than 2 l/min - Uncontrolled arrhythmia or heart failure - Veno-occlusive disease (sinusoidal obstruction syndrome) - Patients with uncontrolled infections |
| Country | Name | City | State |
|---|---|---|---|
| United States | Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| Fred Hutchinson Cancer Research Center | National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number (Percentage) of Patients at Each Dosing Cohort Who Experience no Toxicity and in Whom Graft Versus Host Disease (GVHD) is Stable or Improved | Toxicity and adverse events were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All adverse events were reported regardless of attribution to alpha 1 anti-trypsin (AAT). GVHD response was defined per standard criteria for improvement, no change or progression of signs/symptoms in skin rash (% body surface area), GI (nausea, vomiting, anorexia, diarrhea, GI bleeding, abdominal cramping) and hepatic function (serum bilirubin levels). For this outcome measure, the requirement for additional GVHD treatment beyond AAT was not included in the criteria for response (i.e patients who may have required additional GVHD treatment before study day 28 were not automatically categorized as non-responders or as having progressive GVHD). | Adverse events were reported through 15 days after the last dose of AAT. GVHD response assessed at study day 28. | |
| Secondary | Number (Percentage) of Patients at Each Dosing Cohort Experiencing an Unexpected Serious Adverse Event (SAE) | Serious adverse events included death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/ incapacity, or congenital anomaly/birth defect. Significant events that do not meet these criteria may be considered serious if they jeopardize the patient and require a medical intervention to prevent one of the outcomes above. An "unexpected" adverse event is defined as an event that is not identified in nature, severity or frequency in the current investigator brochure/package insert/product information. | SAEs were reported through 30 days after the last dose of alpha 1 anti-trypsin (AAT). | |
| Secondary | Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Suspected Serious Adverse Reactions (Infusion Related Reactions) | Serious adverse reactions were assessed by the NCI CTCAE v4.0. | Within 48 hours after each infusion | |
| Secondary | Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Thrombotic or Thrombo-embolic Events | Events were assessed using the NCI CTCAE v4.0. | Events were reported through 15 days after the last dose of AAT. | |
| Secondary | Number (Percentage) of Patients at Each Dosing Cohort With Occurrence of Infections | Infections were assessed using NCI CTCAE v4.0. | Infections were reported through 15 days after the last dose of AAT. | |
| Secondary | Number (Percentage) of Patients at Each Dosing Cohort With Progression of GVHD | GVHD responses were assessed using criteria established by the Center for International Blood and Marrow Transplant Research and criteria from the Acute GVHD Activity Index. Patients who required additional systemic GVHD treatment beyond AAT before study day 28 were defined as having progressive GVHD. | GVHD responses were assessed on day 28 after starting AAT therapy or at time of death if patient died before study day 28. |