Allogeneic Stem Cell TransplantationPhase 2BortezomibNCT01929980
Bortezomib to Treat Significant Complication of HSCT
A Phase 2 study testing Bortezomib in people with Allogeneic Stem Cell Transplantation and Refractory Autoimmune Cytopenia(s), run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 months to 29 years
- Conditions the study is for
- Allogeneic Stem Cell Transplantation, Refractory Autoimmune Cytopenia(s)
- What is being tested?
- Bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to May 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 months to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- Ongoing life threatening infections
- Documented anaphylaxis to bortezomib
- Failed engraftment
- Relapse of primary malignancy
- ≥6/8 matched or haploidentical transplants
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: 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.
Read the 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.
- Being tested
- Bortezomib
- Keywords
- HSCT, cytopenia, immune suppression, proteasome inhibitor
- Medical subject headings
- Cytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called PS-341, Velcade
| Study group | Role | What they receive |
|---|---|---|
| Bortezomib | Experimental | 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 Receives: Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2013 (estimated)
- Study startJul 2012
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Allogeneic Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lisa Filipovich, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01929980
- Sponsor's protocol ID
- 2012:1089
- Acronym
- Bortezomib
- Status last verified
- Oct 2016
- First submitted
- 23 Aug 2013
- Last updated
- 24 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Bortezomib to Treat Refractory Autoimmune Cytopenia(s) in Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01929980
- Acronym / sponsor ID
- Bortezomib / 2012:1089
- Keywords
- HSCT, cytopenia, immune suppression, proteasome inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 28 Aug 2013 (estimated)
- Results
- Posted 24 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bortezomib | Experimental | Drug: BortezomibFour 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 |
Who may qualify
- Ages
- 4 months to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- Ongoing life threatening infections
- Documented anaphylaxis to bortezomib
- Failed engraftment
- Relapse of primary malignancy
- ≥6/8 matched or haploidentical transplants
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: PS-341, Velcade | Drug | Bortezomib |
Primary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lisa Filipovich, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib in people with Allogeneic Stem Cell Transplantation and Refractory Autoimmune Cytopenia(s), run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Response (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2016.