Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in Patients With Severe Thrombocytopenia
| Status: | Completed |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 1/5/2019 |
| Start Date: | November 21, 2014 |
| End Date: | August 8, 2017 |
Background:
- Platelets are tiny cells in the blood that help stop bleeding. Thrombocytopenia happens
when people do not have enough normal platelets. Getting a transfusion of another person s
platelets can help stop too much bleeding. But because these cells are from other people, the
body may reject them,putting them at risk for serious bleeding complications. This conditions
is called alloimmune platelet refractoriness . There are evidence that in many patients,
platelet counts fail to increase after a platelet transfusion because the transfused
platelets are destroyed by the body s defence soldier, called complement . Researchers want
to see if a drug, that inhibits complement, can help increase platelet levels and reduce
bleeding
Objectives:
- To see if eculizumab increases platelet levels more after a transfusion. To see if it
reduces the chance of bleeding too much.
Eligibility:
- Adults 18-75 years old who have thrombocytopenia and alloimmune platelet refractoriness.
Design:
- Participants will be screened with medical history, physical exam, and blood tests.
- Participants will have the procedures listed below. They can have them while they are in
the hospital. Or they can go to the outpatient clinic for them. Each visit may take up
to 3 hours.
- Participants will get a meningitis vaccine if needed. Then they will get the study drug
as an infusion.
- Participants will have a platelet transfusion. Their blood will be drawn every 24 hours
until the platelet count is less than 10,000 per 1 microliter of blood.
- They will take antibiotics for 14 days.
- Participants will have a checkup and blood drawn twice a week for 2 weeks. They will get
more transfusions if needed.
- Platelets are tiny cells in the blood that help stop bleeding. Thrombocytopenia happens
when people do not have enough normal platelets. Getting a transfusion of another person s
platelets can help stop too much bleeding. But because these cells are from other people, the
body may reject them,putting them at risk for serious bleeding complications. This conditions
is called alloimmune platelet refractoriness . There are evidence that in many patients,
platelet counts fail to increase after a platelet transfusion because the transfused
platelets are destroyed by the body s defence soldier, called complement . Researchers want
to see if a drug, that inhibits complement, can help increase platelet levels and reduce
bleeding
Objectives:
- To see if eculizumab increases platelet levels more after a transfusion. To see if it
reduces the chance of bleeding too much.
Eligibility:
- Adults 18-75 years old who have thrombocytopenia and alloimmune platelet refractoriness.
Design:
- Participants will be screened with medical history, physical exam, and blood tests.
- Participants will have the procedures listed below. They can have them while they are in
the hospital. Or they can go to the outpatient clinic for them. Each visit may take up
to 3 hours.
- Participants will get a meningitis vaccine if needed. Then they will get the study drug
as an infusion.
- Participants will have a platelet transfusion. Their blood will be drawn every 24 hours
until the platelet count is less than 10,000 per 1 microliter of blood.
- They will take antibiotics for 14 days.
- Participants will have a checkup and blood drawn twice a week for 2 weeks. They will get
more transfusions if needed.
Platelet transfusion can be a life-saving procedure in preventing or treating serious
bleeding in patients who have low and/or dysfunctional platelets. Treatment of blood cancer
and other blood diseases as well as bone marrow transplantation is not possible without
platelet transfusion support. Unfortunately, 20-60% of chronically transfused patients will
stop responding to these transfusions putting them at risk for serious bleeding
complications. Data support the concept that in many patients, platelet counts fail to
increase after a platelet transfusion because the transfused platelets are destroyed by the
body s complement. In order to overcome this problem, we will inhibit complement activity
with the medication eculizumab that specifically binds and suppresses complement. We
hypothesize that when we treat patients who have platelet refractoriness with eculizumab, the
platelet counts will increase to higher numbers after platelet transfusions, decreasing the
risk of bleeding complications associated with having a low platelet count.
bleeding in patients who have low and/or dysfunctional platelets. Treatment of blood cancer
and other blood diseases as well as bone marrow transplantation is not possible without
platelet transfusion support. Unfortunately, 20-60% of chronically transfused patients will
stop responding to these transfusions putting them at risk for serious bleeding
complications. Data support the concept that in many patients, platelet counts fail to
increase after a platelet transfusion because the transfused platelets are destroyed by the
body s complement. In order to overcome this problem, we will inhibit complement activity
with the medication eculizumab that specifically binds and suppresses complement. We
hypothesize that when we treat patients who have platelet refractoriness with eculizumab, the
platelet counts will increase to higher numbers after platelet transfusions, decreasing the
risk of bleeding complications associated with having a low platelet count.
- INCLUSION CRITERIA:
- Ages 18-75 years inclusive.
- Ability to comprehend the investigational nature of the study and provide informed
consent.
- Thrombocytopenia (due to congenital causes, bone marrow failure, hematologic
malignancies, and treatment related), defined as <10k/uL without bleeding or <30K/uL
with evidence of life threatening bleeding (intracranial hemorrhage, GI bleeding,
pulmonary hemorrhage, uncontrolled epistaxis, hematuria).
- Diagnosed with immune platelet refractoriness, characterized by all of the following:
- Lack of adequate post-transfusion platelet count increment, defined by, CCI
<7500/ul at 10-60 min, and CCI <5000/ul at 18-24 hrs (in those who had a CCI at
10-60 min greater than or equal to 5000/microl)after at least 2 consecutive
transfusions.
- Presence of anti-HLA class A and/or B antibody.
EXCLUSION CRITERIA:
- Active meningococcal infection.
- Severe psychiatric illness. Mental deficiency sufficiently severe as to make making
informed consent impossible.
- Positive pregnancy test for women of childbearing age within 1 week.
- HIV positive test within 3 months
- Paroxysmal Nocturnal Hemoglobinuria (PNH) disease with evidence of intravascular
hemolysis.
- Presence ITP/autoimmune thrombocytopenia
- Immune platelet refractoriness responsive to treatment with IVIG
RE-ENROLLMENT CRITERIA:
- Meet response criteria to the initial treatment or second treatment
- Meets all initial inclusion/exclusion criteria
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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