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

Lymphoma Clinical Trial

Official title:

Bortezomib-based Graft-Versus-Host-Disease Prophylaxis After Myeloablative Allogeneic Stem Cell Transplantation for Patients Lacking HLA-matched Related Donors: A Phase 2 Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01323920
• Other study ID #: 11-007
• Status: Completed
• Phase: Phase 2
• First received: March 24, 2011
• Last updated: May 23, 2017
• Start date: May 2011
• Est. completion date: November 2013

Study information

• Verified date: May 2017
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor.

You will receive 3 drugs for your GVHD prophylaxis:

Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant.

Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant.

Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: November 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Bortezomib
Bortezomib 1.3 mg/m^2 IV
• Tacrolimus
Tacrolimus 0.05 mg/kg PO bid
• Methotrexate
Methotrexate 15 mg/m^2 IV

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion	To assess the percentage donor engraftment up to day 30 post stem cell infusion, defined as the first of 3 consecutive days tested of documented absolute netrophil count (ANC) >/= 500 cells/u/L	Day 30
Secondary	The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion	Progression free and overall survival by 1 year after stem cell infusion will be assessed using the method of Kaplan and Meier. Progression-free survival will be defined as the time from stem cell infusion to the time of disease progression or death from any cause. Overall survival will be defined as the time from stem cell infusion to the time to death from any cause. Patients will be censored at the time last documented alive. Cumulative incidence and Kaplan-Meier curves will be constructed as appropriate. Progression is defined per clinical presentation, not protocol specified, and vary per disease, e.g. blasts in bone marrow or peripheral blood for AML/MDS; lymphoma + on PET/CT re-staging etc.	1 year
Secondary	The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion		1 year