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

Dana-Farber Cancer Institute

Status and phase: Completed; Phase 2

Conditions: Lymphoma; Myelodysplastic Syndrome; Leukemia

Treatments: Drug: Tacrolimus; Drug: Bortezomib; Drug: Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT01323920

11-007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

Velcade/Tac/MTX

Experimental group

Description:

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

Treatment:

Drug: Bortezomib

Drug: Methotrexate

Drug: Tacrolimus