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Bortezomib to Treat Significant Complication of HSCT (Bortezomib)

Primary Purpose

Allogeneic Stem Cell Transplantation, Refractory Autoimmune Cytopenia(s)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bortezomib
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Allogeneic Stem Cell Transplantation focused on measuring HSCT, cytopenia, immune suppression, proteasome inhibitor

Eligibility Criteria

4 Months - 29 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cincinnati Children's Hospital Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bortezomib

Arm 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

Outcomes

Primary Outcome Measures

Number of Participants With Response
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

Secondary Outcome Measures

Full Information

First Posted
August 23, 2013
Last Updated
October 18, 2016
Sponsor
Children's Hospital Medical Center, Cincinnati
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1. Study Identification

Unique Protocol Identification Number
NCT01929980
Brief Title
Bortezomib to Treat Significant Complication of HSCT
Acronym
Bortezomib
Official Title
Use of Bortezomib to Treat Refractory Autoimmune Cytopenia(s) in Allogeneic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
May 2014 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allogeneic Stem Cell Transplantation, Refractory Autoimmune Cytopenia(s)
Keywords
HSCT, cytopenia, immune suppression, proteasome inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bortezomib
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
PS-341, Velcade
Primary Outcome Measure Information:
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Months
Maximum Age & Unit of Time
29 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa Filipovich, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States

12. IPD Sharing Statement

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Bortezomib to Treat Significant Complication of HSCT

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