Bortezomib to Treat Significant Complication of HSCT
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: Bortezomib
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Response [6 weeks]
For Autoimmune Hemolytic Anemia- At least 3 of 5 criteria should be met. Stabilization of hemoglobin without transfusions by 2 weeks Conversion of DAT from + to - by 6 weeks Normalization of serum haptoglobin levels by 6 weeks Normalization of indirect bilirubin levels by 6 weeks Reduction in the frequency of transfusions by 50% by 4 weeks For Autoimmune Neutropenia- At least 2 of 3 criteria should be met. Stabilization of absolute neutrophil count by 2 weeks Undetectable antineutrophil antibodies by 6 weeks Reduction in GCSF dose by 50% by 6 weeks For Autoimmune Thrombocytopenia- At least 2 of 3 criteria should be met. Stabilization of platelet count without platelet transfusions by 2 weeks Undetectable antiplatelet antibodies by 6 weeks Reduction in the frequency of platelet transfusions by 50% from pre-bortezomib values by 6 weeks
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
Sponsors and Collaborators
- Children's Hospital Medical Center, Cincinnati
Investigators
- Principal Investigator: Lisa Filipovich, MD, Children's Hospital Medical Center, Cincinnati
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2012:1089
- NCT01930253
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Bortezomib |
|---|---|
| Arm/Group Description | 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 |
| Period Title: Overall Study | |
| STARTED | 4 |
| COMPLETED | 3 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Bortezomib |
|---|---|
| Arm/Group Description | 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 |
| Overall Participants | 4 |
| Age (Count of Participants) | |
| <=18 years |
4
100%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
25%
|
| Male |
3
75%
|
Outcome Measures
| Title | Number of Participants With Response |
|---|---|
| Description | For Autoimmune Hemolytic Anemia- At least 3 of 5 criteria should be met. Stabilization of hemoglobin without transfusions by 2 weeks Conversion of DAT from + to - by 6 weeks Normalization of serum haptoglobin levels by 6 weeks Normalization of indirect bilirubin levels by 6 weeks Reduction in the frequency of transfusions by 50% by 4 weeks For Autoimmune Neutropenia- At least 2 of 3 criteria should be met. Stabilization of absolute neutrophil count by 2 weeks Undetectable antineutrophil antibodies by 6 weeks Reduction in GCSF dose by 50% by 6 weeks For Autoimmune Thrombocytopenia- At least 2 of 3 criteria should be met. Stabilization of platelet count without platelet transfusions by 2 weeks Undetectable antiplatelet antibodies by 6 weeks Reduction in the frequency of platelet transfusions by 50% from pre-bortezomib values by 6 weeks |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Bortezomib |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 4 |
| Neutropenia (n=3) |
3
75%
|
| Thrombocytopenia (n=2) |
2
50%
|
| Hemolytic Anemia (n=1) |
1
25%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Bortezomib | |
| Arm/Group Description | 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 | |
All Cause Mortality |
||
| Bortezomib | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Bortezomib | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | |
| Blood and lymphatic system disorders | ||
| Thrombocytopenia | 1/4 (25%) | 1 |
| Neutropenia | 1/4 (25%) | 1 |
| Gastrointestinal disorders | ||
| Pneumatosis Coli | 1/4 (25%) | 1 |
| Infections and infestations | ||
| C diff colitis | 1/4 (25%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Bortezomib | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/4 (25%) | |
| Gastrointestinal disorders | ||
| Nausea | 1/4 (25%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Cellulitis | 1/4 (25%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Pooja Khandelwal, MD |
|---|---|
| Organization | Cincinnati Children's Hospital Medical Center |
| Phone | 513-803-9063 |
| Pooja.Khandelwal@cchmc.org |
- 2012:1089
- NCT01930253