Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors

NCT01323920 | Completed Phase 2 Results DMC

• 1 other identifier: 11-007
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD. In this research study, we are studying the safety and effectiveness of a bortezomib based GVHD prophylaxic drug combination in participants after myeloablative allogeneic stem call transplantation from a matched unrelated donor, mismatched related or unrelated donor.

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndrome

Keywords

Stem Cell Transplant; Allogeneic Transplant; Donors

Outcome Measures

Primary Outcomes (1)

• The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion

  The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.

  Day 100

Secondary Outcomes (3)

• The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion

  Day 30

• The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion

  1 year

• The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion

  1 year

Study Arms (1)

Velcade/Tac/MTX

EXPERIMENTAL

Drug: Bortezomib. Other Names: Velcade. Bortezomib 1.3 mg/m\^2 IV Drug: Tacrolimus. Tacrolimus 0.05 mg/kg PO bid Drug: Methotrexate. Methotrexate 15 mg/m\^2 IV

Drug: Bortezomib; Drug: Tacrolimus; Drug: Methotrexate

Interventions

Bortezomib DRUG

Bortezomib 1.3 mg/m\^2 IV

Also known as: Velcade

Velcade/Tac/MTX

Tacrolimus DRUG

Tacrolimus 0.05 mg/kg PO bid

Velcade/Tac/MTX

Methotrexate DRUG

Methotrexate 15 mg/m\^2 IV

Velcade/Tac/MTX

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including myelodysplastic syndrome) that is unlikely to be cured by alternative therapies
• HLA-Matched unrelated donor; or 1-locus HLA-mismatched related or unrelated donor
• ECOG performance status 0-2
• Adequate organ function
• Able to understand and willing to sign a written informed consent document
• Agrees to practice adequate contraception per study requirements

You may not qualify if:

• Pregnant or breastfeeding
• Recipient of prior allogeneic or autologous stem cell transplantation
• Prior abdominal radiation therapy
• HIV-positive on combination antiretroviral therapy
• Seropositive for hepatitis B or C
• Allergies to bortezomib, boron, or mannitol
• Myocardial infarction within last 6 months, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias
• Uncontrolled bacterial, viral or fungal infections
• Seizures or history of seizures
• History of another non-hematologic malignancy unless disease-free for at least 5 years
• Uncontrolled intercurrent illness

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Koreth J, Kim HT, Lange PB, Bindra B, Reynolds CG, Chammas MJ, Armand P, Cutler CS, Ho VT, Glotzbecker B, Nikiforow S, Ritz J, Blazar BR, Soiffer RJ, Antin JH, Alyea EP 3rd. A Bortezomib-Based Regimen Offers Promising Survival and Graft-versus-Host Disease Prophylaxis in Myeloablative HLA-Mismatched and Unrelated Donor Transplantation: A Phase II Trial. Biol Blood Marrow Transplant. 2015 Nov;21(11):1907-13. doi: 10.1016/j.bbmt.2015.05.027. Epub 2015 Jun 6.

  PMID: 26055298 DERIVED

MeSH Terms

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes

Interventions

Bortezomib; Tacrolimus; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. John Koreth
• Organization: Dana Farber Cancer Institute

John_Koreth@dfci.harvard.edu

617-632-2949

Study Officials

• John Koreth, MBBS, DPhil

  Dana-Farber Cancer Institute

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 24, 2011
• First Posted: March 28, 2011
• Study Start: May 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: November 1, 2013
• Last Updated: May 30, 2017
• Results First Posted: March 31, 2014

Record last verified: 2017-05

Locations

US (1)