Bortezomib Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched Allogeneic Non-Myeloablative Blood Stem Cell Transplantation

Dana-Farber Cancer Institute

Status and phase

Completed

Phase 2

Phase 1

Conditions

Hematologic Malignancies

Treatments

Drug: Methotrexate

Procedure: blood stem cell transplantation

Drug: Bortezomib (Velcade)

Drug: Tacrolimus

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00369226

06-065

X05175

Details and patient eligibility

About

The purpose of this study is to determine if Velcade (also known as bortezomib) can help prevent graft versus host disease (GVHD) developing after transplantation. This is done by using a combination of three immune suppressive medications: Velcade, tacrolimus and methotrexate. Stem cell transplantation is one of the options for patients with cancer of the blood or blood forming organs. Recently, allogeneic stem cell transplants have been performed using lower doses of chemotherapy and radiotherapy: non-myeloablative or "mini" transplants. GVHD is a significant problem that may occur even after "mini" transplantations. Information from other research studies, suggests that Velcade may help to reduce the risk of developing GVHD when given early after transplantation.

Full description

In this study we are looking for the highest dose of Velcade that can be given to people safely when given with tacrolimus and methotrexate. Not everyone who participates in the study will receive the same amount of the study drug. The dose the participant will receive depends upon the number of subjects enrolled on the study and how well they have tolerated their doses of the drug.
Before Transplant: In addition to the chemotherapy drugs, fludarabine and busulfex, for the participants non-myeloablative transplant, they will also start taking tacrolimus orally three days before their transplant.
After Transplant Medication: Methotrexate; Intravenously on days 1, 3, 6 & 11 after transplant for a total of 4 doses. Tacrolimus; Continue taking orally once daily. Velcade: Intravenously on days 1, 4 & 7 after transplant, a total of 3 doses. Filgrastim: Subcutaneous injection daily starting the day after transplant and continuing until the participant blood counts have recovered.
After Transplant Physical Exams & Tests: Participants will have physical exams and blood tests every week for 1 month. After 1 month, a none marrow biopsy will be performed to look for evidence of the donor's cells in the participants bone marrow.
Following the 1 month period of time, participants will be seen every few weeks. Another bone marrow biopsy, as well as blood tests, will be taken 3-4 months after the transplant to review the disease status. At this point, participants will come into the clinic about every 3 months, or as determined by their physician for about one year.
While the study ends at 12 months after transplant, we would like to keep track of the participants medical condition for the rest of their life.

Enrollment

45 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with hematologic malignancies including myelodysplastic syndrome (MDS), who are at a high risk of complications after myeloablative transplantation
Patients have a donor (both related and unrelated) who are mismatched according to protocol criteria
18 years of age or older
Performance status 0-2
Life expectancy of > 100 days
Female subject is either post-menopausal or sterilized or willing to use an acceptable form of birth control
Male subject agrees to use an acceptable form of birth control

Exclusion criteria

Evidence of HIV infection
Total bilirubin > 2.0mg/dl that is due to hepatocellular dysfunction
Aspartate aminotransferase (AST) > 90
Known active hepatitis B or C
Serum creatinine > 2.0
Greater than or equal to Grade 2 peripheral neuropathy within 21 days of enrollment
Prior allogeneic stem cell transplant
Patients with myeloproliferative disease (e.g. myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia)
Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
Hypersensitivity to Velcade, boron or mannitol
Pregnant or breast feeding
Patient has received other investigational drugs 14 days before enrollment
Serious medical or psychiatric illness
Another active solid tumor malignancy at the time of study entry