Standard of Care vs. Bortezomib in Graft-Versus Host Disease After Hematopoietic Stem Cell Transplant

Status: Recruiting
Phase: Phase 2
Diagnosis: Hematopoietic Stem Cell Transplant
NCT ID: NCT01754389 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 12-404

 

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA has not yet approved bortezomib to treat or prevent graft-versus-host disease. Bortezomib is approved by the FDA to treat other human malignancies. Bortezomib is a drug that has an anti-cancer effect that involves inhibiting cell growth and causing cell death. This drug has been used in other research studies, and information from thos other research studies suggests that bortezomib may help to lower the risk of GVHD after allogeneic stem cell transplantation in patients who have matched unrelated, unmatched related or unrelated donors in this research study. Allogeneic stem cell transplantation is a procedure in which selected blood cells taken from your sibling or unrelated donor are given to you. Lower doses of chemotherapy drugs are given before the donor cells are infused in a process known as reduced-intensity conditioning. Stem cell transplant destroys cancer in two ways: The conditioning regimen destroys cancer cells and teh immune cells from the donor can recognize cancer cells and kill them. A common problem after stem cell transplant is graft-versus-host disease (GVHD). The word "graft" refers to the donor blood cells that you will receive during your transplant. The word "host" refers to the person (in this case, you) receiving the cells. GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. GVHD can cause skin rash, intestinal problems such as nausea, vomiting or diarrhea. GVHD may also damage your liver and cause hepatitis or jaundice. GVHD may also increase your risk of infection. After stem cell transplant, all patients receive prophylactic medications against GVHD. In this research study we are studying the safety and effectiveness of preventing GVHD using bortezomib treatment in combination with other drugs versus standard of care prophylaxis (tacrolimus + methotrexate). If you take part in this study, there is a 33% chance you will receive any one of the following GVHD prevention treatments: - tacrolimus + methotrexate (standard of care GVHD prophylaxis) - bortezomib + tacrolimus + methotrexate - bortezomib + sirolimus + tacrolimus Sirolimus, tacrolimus and methotrexate are drugs that suppress the immune system to try to prevent GVHD.

 

Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital

Overall PI:
John Koreth, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:
Bimalangshu Dey, MD, Massachusetts General Hospital

Contacts:
Dana-Farber Cancer Institute: Mildred Pasek, mpasek@partners.org
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

Inclusion Criteria: - Histologically or cytologically confirmed advanced/aggressive hematologic malignancy unlikely to be cured by alternative therapies - HLA matched unrelated donors or 1-locus HLA mismatched related or unrelated donors - Adequate organ function - Willing to use appropriate contraception Exclusion Criteria: - Pregnant or breastfeeding - Recipient of prior allogeneic hematopoietic stem cell transplantation - Recipient of prior abdominal radiation therapy - HIV positive on combination anti-retroviral therapy - Seropositive for hepatitis B or C - Known allergy to bortezomib, boron or mannitol - Myocardial infarction within 6 months prior to enrollment or any other cardiac dysfunction - Uncontrolled infection - Inability to withhold agents that may interact with hepatic cytochrome P450 enzymes or gluthathione S-transferases - Seizures or history of seizures - Grade greater than or equal to 2 peripheral neuropathy within 21 days of enrollment - Use of other investigational drugs within 21 days of enrollment - History of another non-hematologic malignancy except if disease free for at least 5 years or cervical cancer in situ, or basal/squamous cell carcinoma of the skin - Uncontrolled intercurrent illness
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