Bortezomib to Treat Significant Complication of HSCT (Bortezomib)

October 18, 2016 updated by: Children's Hospital Medical Center, Cincinnati

Use of Bortezomib to Treat Refractory Autoimmune Cytopenia(s) in Allogeneic Stem Cell Transplantation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 months to 29 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • Velcade
  • PS-341

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Response
Time Frame: 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
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Investigators

  • Principal Investigator: Lisa Filipovich, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2012

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

August 23, 2013

First Submitted That Met QC Criteria

August 23, 2013

First Posted (Estimate)

August 28, 2013

Study Record Updates

Last Update Posted (Estimate)

October 24, 2016

Last Update Submitted That Met QC Criteria

October 18, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012:1089

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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