Allogeneic Stem Cell Transplantation, Refractory Autoimmune Cytopenia(s)
Conditions
Keywords
HSCT, cytopenia, immune suppression, proteasome inhibitor
Brief summary
The purpose of this trial is to study the safety and effectiveness of a drug called Bortezomib for the treatment of low blood cell counts after bone marrow transplant.
Detailed description
The purpose of this research study is to study the safety and effectiveness of a drug called bortezomib for the treatment of autoimmune cytopenia(s) (low blood cell counts) after bone marrow transplant that are not responding to standard treatments. Autoimmune cytopenias are low blood counts due to antibodies or proteins produced against an individual's own blood cells. Having a low red blood cell count (anemia) can make a person feel tired and require blood transfusions frequently. A low platelet count (blood cells that help blood to clot) can make a person bleed or bruise easily. A low neutrophil (white blood cell) count can make a person have infections. All of these things can be a serious complication after bone marrow transplant and can cause prolonged hospital stay. Bortezomib is being used in children with certain types of blood cancer, however, bortezomib has not been used in children with autoimmune cytopenia(s) and its use in this study is investigational.
Interventions
DRUGBortezomib
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Months to 29 Years
Healthy volunteers
No
Inclusion criteria
* All patients, having undergone allogeneic stem cell transplantation at our center. * Should have failed at least 2 standard treatments for autoimmune cytopenias. Standard treatments include corticosteroids, rituximab, IVIG, plasmapheresis, withdrawal of cyclosporine, cyclophosphamide and MMF. Definition of failed treatment will be no response of cytopenia after 2 weeks of continued treatment OR requirement of daily GCSF at 10 mcgs/kg/day for autoimmune neutropenia despite 2 weeks of treatment, transfusions of packed red blood cells or platelets 3 times weekly for 2weeks despite continued treatment OR 5days/week plasmapheresis for 2 weeks and inability to wean the duration. * Definition of autoimmune hemolytic anemia- development of anemia, where there is a hemoglobin drop of \>2 g/dL/48 hours or an absolute value of hemoglobin \< 8 g/dL, and evidence of hemolysis by positive direct Coombs test with compatible peripheral blood cell morphology, reticulocyte count and bilirubin level. * Definition of autoimmune neutropenia - absolute neutrophil counts \< 500 for 2 weeks and presence of anti-neutrophil antibodies. * Definition of autoimmune thrombocytopenia- Platelet counts \< 20,000 cells/uL for 2 weeks and presence of anti-platelet antibodies.
Exclusion criteria
* Ongoing life threatening infections * Documented anaphylaxis to bortezomib * Failed engraftment * Relapse of primary malignancy * ≥6/8 matched or haploidentical transplants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response | 6 weeks | For Autoimmune Hemolytic Anemia- At least 3 of 5 criteria should be met. 1. Stabilization of hemoglobin without transfusions by 2 weeks 2. Conversion of DAT from + to - by 6 weeks 3. Normalization of serum haptoglobin levels by 6 weeks 4. Normalization of indirect bilirubin levels by 6 weeks 5. Reduction in the frequency of transfusions by 50% by 4 weeks For Autoimmune Neutropenia- At least 2 of 3 criteria should be met. 1. Stabilization of absolute neutrophil count by 2 weeks 2. Undetectable antineutrophil antibodies by 6 weeks 3. Reduction in GCSF dose by 50% by 6 weeks For Autoimmune Thrombocytopenia- At least 2 of 3 criteria should be met. 1. Stabilization of platelet count without platelet transfusions by 2 weeks 2. Undetectable antiplatelet antibodies by 6 weeks 3. Reduction in the frequency of platelet transfusions by 50% from pre-bortezomib values by 6 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bortezomib Four doses of bortezomib, 1.3mg/m2, will be given intravenously (through a needle in a vein) or subcutaneously (under the skin) on Days 1, 4, 8, 11.
The format of receiving medications is- Therapy Dose and Route Frequency Rituximab 375 mg/m2 intravenously Once on day 1. Plasmapheresis 2 hours prior to Bortezomib Day 1,4, 8 and 11 Bortezomib 1.3 mg/m2 intravenously Day 1,4,8 and 11
Bortezomib | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Bortezomib |
|---|---|
| Age, Categorical <=18 years | 4 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
Number of Participants With Response
For Autoimmune Hemolytic Anemia- At least 3 of 5 criteria should be met. 1. Stabilization of hemoglobin without transfusions by 2 weeks 2. Conversion of DAT from + to - by 6 weeks 3. Normalization of serum haptoglobin levels by 6 weeks 4. Normalization of indirect bilirubin levels by 6 weeks 5. Reduction in the frequency of transfusions by 50% by 4 weeks For Autoimmune Neutropenia- At least 2 of 3 criteria should be met. 1. Stabilization of absolute neutrophil count by 2 weeks 2. Undetectable antineutrophil antibodies by 6 weeks 3. Reduction in GCSF dose by 50% by 6 weeks For Autoimmune Thrombocytopenia- At least 2 of 3 criteria should be met. 1. Stabilization of platelet count without platelet transfusions by 2 weeks 2. Undetectable antiplatelet antibodies by 6 weeks 3. Reduction in the frequency of platelet transfusions by 50% from pre-bortezomib values by 6 weeks
Time frame: 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bortezomib | Number of Participants With Response | Neutropenia (n=3) | 3 participants |
| Bortezomib | Number of Participants With Response | Thrombocytopenia (n=2) | 2 participants |
| Bortezomib | Number of Participants With Response | Hemolytic Anemia (n=1) | 1 participants |