A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease
| Status: | Completed |
|---|---|
| Conditions: | Orthopedic, Hematology |
| Therapuetic Areas: | Hematology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 11/29/2018 |
| Start Date: | July 2013 |
| End Date: | October 26, 2018 |
This clinical trial will study the safety and efficacy of using the drug Zemaira, an Alpha
1-Antitrypsin (AAT) medication (also known as an Alpha1-Proteinase Inhibitor [Human]) for the
treatment of steroid refractory GVHD.
For bone marrow transplant patients, the most common, serious complication is Graft vs Host
Disease (GVHD), which at its most severe is a life-threatening, complication and a
significant cause of treatment related death, following stem cell transplantation. GVHD is a
major obstacle to the overall success of transplant treatment, a strategy that would
otherwise provide the possibility of a cure for patients with blood cancers or severe blood
disorders. GVHD primarily affects the skin, gut, and liver of the recipient, and involves the
interaction of the recipient's (the host's) cells and tissues with the donor's immune system
cells that see the host tissues as foreign, and attack the host's cells resulting in tissue
and organ damage.
The severity of acute GvHD ranges from mild to severe, and for patients who don't respond to
steroid therapy, the complication is nearly always fatal, either from organ damage or
opportunistic infection as a consequence of high dose, steroid treatments.
There is currently no known effective therapy for patients with acute graft vs host disease
that's refractory (nonresponsive) to steroid therapy. As stated earlier,the overwhelming
majority of these patients may ultimately die from infection. The incidence of acute GvHD
that requires intervention, is higher for unrelated donor transplants, the most common
treatment option available, and therefore, these patients are at higher risk for treatment
related complications from GVHD. Approximately 20,000 unrelated donor transplants are
performed each year. The magnitude of this problem then is significant for patients who
otherwise might be cured of their blood cancer or disease.
1-Antitrypsin (AAT) medication (also known as an Alpha1-Proteinase Inhibitor [Human]) for the
treatment of steroid refractory GVHD.
For bone marrow transplant patients, the most common, serious complication is Graft vs Host
Disease (GVHD), which at its most severe is a life-threatening, complication and a
significant cause of treatment related death, following stem cell transplantation. GVHD is a
major obstacle to the overall success of transplant treatment, a strategy that would
otherwise provide the possibility of a cure for patients with blood cancers or severe blood
disorders. GVHD primarily affects the skin, gut, and liver of the recipient, and involves the
interaction of the recipient's (the host's) cells and tissues with the donor's immune system
cells that see the host tissues as foreign, and attack the host's cells resulting in tissue
and organ damage.
The severity of acute GvHD ranges from mild to severe, and for patients who don't respond to
steroid therapy, the complication is nearly always fatal, either from organ damage or
opportunistic infection as a consequence of high dose, steroid treatments.
There is currently no known effective therapy for patients with acute graft vs host disease
that's refractory (nonresponsive) to steroid therapy. As stated earlier,the overwhelming
majority of these patients may ultimately die from infection. The incidence of acute GvHD
that requires intervention, is higher for unrelated donor transplants, the most common
treatment option available, and therefore, these patients are at higher risk for treatment
related complications from GVHD. Approximately 20,000 unrelated donor transplants are
performed each year. The magnitude of this problem then is significant for patients who
otherwise might be cured of their blood cancer or disease.
Inclusion Criteria:
- Age >18 years
- Patients must have clinical evidence* of steroid-refractory acute Graft vs Host
Disease (any organ) defined as one of the following:
- No change or progression in the stage of skin GvHD after at least 1 week of
2mg/kg/day methylprednisolone (or po equivalent)
- lack of response of visceral (liver, GI) GvHD despite treatment with 2mg/kg/day
methylprednisolone for at least 72h.
- progression of visceral GvHD despite treatment with 2mg/kg/day methylprednisolone
for at least 48h
- visceral GvHD progressing to stage 4 after 24h of 2mg/kg/d methylprednisolone
- Patients with protracted acute GvHD who have not responded to at least 0.5mg/kg/d
of prednisone are considered eligible.
- Ability to understand and the willingness to sign a written informed consent document.
- * As GvHD is a clinical diagnosis, and patients will have already been initiated on
steroid therapy at the discretion of the attending physician, tissue confirmation of
refractory GvHD by biopsy is not required for entry to this study. It is anticipated
that most, but not all, patients will have undergone tissue confirmation of the
initial diagnosis of GvHD; however lack of tissue confirmation for this clinical
syndrome is not exclusionary.
Exclusion Criteria:
- As patients with steroid refractory acute GvHD are quite ill with multiple abnormal
labs and organ dysfunction, there are no explicit laboratory values or degree of organ
dysfunction that specifically preclude enrollment on this study. Baseline lab studies
will be obtained and followed throughout this trial as the standard of care for
patients with GvHD.
- Pregnancy or Nursing Mother
- Vasopressor requirement
- Patients may not be receiving any other investigational agents for the treatment of
GvHD at time of study entry or at any time while on study or be on another
investigational agent that can impact on the primary clinical outcome analyses or has
known pharmacodynamics or pharmacokinetic effects on AAT.
- Patients with known antibodies to IgA
We found this trial at
2
sites
450 Brookline Ave
Boston, Massachusetts 2215
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: John Koreth, MD, PhD
Phone: 617-632-2949
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Ann Arbor, Michigan 48109
Principal Investigator: Pavan Reddy, MD
Phone: 734-936-6884
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