Bortezomib to Treat Significant Complication of HSCT

NCT01929980 | Completed Phase 2 Results DMC

• 1 other identifier: 2012:1089
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Allogeneic Stem Cell Transplantation; Refractory Autoimmune Cytopenia(s)

Keywords

HSCT; cytopenia; immune suppression; proteasome inhibitor

Outcome Measures

Primary Outcomes (1)

• 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

  6 weeks

Study Arms (1)

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

Drug: Bortezomib

Interventions

Bortezomib DRUG

Also known as: PS-341, Velcade

Bortezomib

Eligibility Criteria

• Age: 4 Months - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Ongoing life threatening infections
• Documented anaphylaxis to bortezomib
• Failed engraftment
• Relapse of primary malignancy
• ≥6/8 matched or haploidentical transplants

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Cytopenia

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pooja Khandelwal, MD
• Organization: Cincinnati Children's Hospital Medical Center

Pooja.Khandelwal@cchmc.org

513-803-9063

Study Officials

• Lisa Filipovich, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2013
• First Posted: August 28, 2013
• Study Start: July 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: October 24, 2016
• Results First Posted: October 24, 2016

Record last verified: 2016-10

Locations

US (1)