Clinical trial NCT01323920: Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Myelodysplastic Syndrome
Keywords: Stem Cell Transplant
Allogeneic Transplant
Donors
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2011-03-28
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion
timeFrame: Day 100
Secondary outcomes:
measure: The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion
timeFrame: Day 30
measure: The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion
timeFrame: 1 year
measure: The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion
timeFrame: 1 year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: John Koreth, MBBS, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.