IMMUNE TOLERANCE INDUCTION
HLA MATCHED LIVING DONOR
KIDNEY AND BONE MARROW TRANSPLANTATION
A Phase 3 Prospective, Randomized, Multi-Center, Open-Label, Controlled Trial to Assess the Efficacy and Safety of Cellular Immunotherapy with MDR-101 for Induction of Immune Tolerance in Recipients of HLA-matched, Living Donor Kidney Transplants.
Funded by: Medeor Therapeutics, Inc.
INFORMATION FOR RECIPIENTS
Who can participate? Patients scheduled to receive a kidney transplant and plan on being a recipient of a first kidney allograft from an HLA-matched, living related donor.
What is the procedure? The purpose of this study is to determine if a single infusion of MDR-101 can prevent the immune system from rejecting a transplanted kidney without any or minimal anti-rejection drugs. MDR-101 is made from stem cells from the blood of the kidney donor. MDR-101 will be given to the kidney recipient to see if the immune system can be reprogrammed. The study drug MDR-101 has not been approved by the United States Food and Drug Administration (FDA) for kidney transplants and is considered experimental.
There are several parts to this procedure.
First, your donor will be given a drug called granulocyte-colony stimulating factor (G-CSF) which causes the bone marrow to release large numbers of stem cells into the blood stream. Stem cells are cells that can become all the different cells in the blood. They normally live in the bone marrow in the center of the bones, they are also found in the blood in very small numbers. (G-CSF is approved by the FDA to help in the production of stem cells).
Then, these stem cells are collected by a special machine called apheresis. The apheresis machine captures the stem cells only and returns the remaining blood product back to the donor.
Participation means that you and your kidney donor will be randomly assigned (like the flip of a coin) to one of the study groups (control or MDR-101).
Anti-thymocyte Gobulin (ATG) Induction therapy: You will be given ATG intraveously (IV) infusion through a vein in your arm, once a day for five days. ATG is an anti-rejection drug approved by the FDA for transplant patients.
Total Lymphoid Irradiation (TLI) Conditioning Therapy: Radiation (x-rays) will be directed at the lymph nodes in the abdomena dn the chest. Radiation will be given once daily for several days with a total of 10 radiation doses.
MDR-101: you will receive a single IV infusion of MDR-101 over approx 10-20 minutes. Your dose of MDR-101 will be made using the stem cells from your kidney donor.
You will start to take an immunosuppressive drug which is approved by the FDA for transplant patients.
You will receive the routine drugs as decided by your transplant physician.
Information concerning your kidney donor: if randomized to the MDR-101 group, your donor will inject G-CSF for 5 days, and on the 5th day undergo apheresis. (more descriptive on the donor description page_.
Participation in this study will involve approximately 71 study visits. This will include 1-3 study visits pre-transplant, up to 8 post transplant visits depending on how long you remain in the hospital, and about 60 extended post-transplant visits. For required follow up visits, the cost of travel will be reimbursed.
What are the risks?
•MDR-101: carries similar risk to the infusion of many biologic materials. Most common reactions include: fever, chills, generalized muscle, joint pain, anemia.
*Graft vs Host DIsease
* ATG risk: most common, fever, chills, allergic reaction.
*TLI risk: depression of the bone marrow which is usually transient and should wear off in a couple days of up to a few weeks, nausea, loss of appetite, weakness. The side effects should wear off in 2-3 days when the radiation is stopped.
*If you are a woman who is able to become pregnant, it is expected that you will use an effective method of birth control while you are participating in this study.
What are the benefits?
•You may benefit from being closely watched by the study team coordinators and Dr. Witkowski.
•You will help scientists learn how to improve therapy for other patients undergoing kidney transplant in the future.
The decision whether or not you wish to participate in this study will not affect your care at the University of Chicago Medical Center.
Have there been any unexpected complications in the previous study?
No, The risk to the cell and organ donors who participated in the previous study (phase 2) appear to have been minimal and the apheresis required was not associated with significant complications.
Are there any preliminary results indicating potential for success?
The MDR-101 cell product has been already used in the study in limited number of patients (phase 2 study) and found safe and results indicated some effectiveness. Now, it is being tested on a larger group of patients to confirm its effectiveness and safety.