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

Phase 2

Completed

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.

Recruitment & 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

Arm && Interventions

Group	Intervention	Description
Velcade/Tac/MTX	Bortezomib	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
Velcade/Tac/MTX	Tacrolimus	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
Velcade/Tac/MTX	Methotrexate	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

Primary Outcome Measures

Name	Time	Method
The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion	Day 100	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.

Secondary Outcome Measures

Name	Time	Method
The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion	1 year
The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion	1 year	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.
The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion	Day 30	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

Locations (1): Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States