NCT02029638

BMT and High Dose Post-Transplant Cyclophosphamide for Chimerism Induction and Renal Allograft Tolerance

Bone Marrow Transplantation and High Dose Post-Transplant Cyclophosphamide for Chimerism Induction and Renal Allograft Tolerance (ITN054ST)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this study is to assess the ability of bone marrow transplantation (BMT) and high-dose post-transplantation cyclophosphamide (PT/Cy) to induce renal allograft tolerance and thus enable discontinuation of immunosuppressive therapy in haploidentical living related donor renal transplant recipients.

Detailed description

Transplantation is a good treatment for people with end-stage kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it working for a long time. Unless a person receiving a kidney from someone else takes drugs that reduce immune function, the kidney will be rejected. Those drugs must be continued life-long and cause many issues. Therefore, tolerance of the transplanted kidney, without chronic rejection and without the need for permanent immunosuppressive drug treatment, is a highly desirable goal. If this can be achieved, it would make "one kidney for life" possible. The study treatment includes several days of study medications followed by a kidney and bone marrow transplant. After the transplant, the study treatment will continue with a few more doses of study medications and then anti-rejection medication is started. After a while, the anti-rejection medication is slowly stopped. Researchers will examine blood and tissue samples and try to identify genetic markers for certain conditions like chimerism, response to therapy, and tolerance. \*\*\* IMPORTANT NOTICE: \*\*\* The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.

Conditions

• Kidney Transplantation

Interventions

Type	Name	Description
BIOLOGICAL	anti-thymocyte globulin	An initial dose of 0.5 mg/kg IV will be administered over 6 hours on Day -9. Thereafter the daily dose will be increased to 2 mg/kg IV given over 4 hours on Days -8 and -7. No more than 150 mg of ATG may be administered per day.
DRUG	Fludarabine	Fludarabine at dose 30 mg/m\^2 will be administered daily by intravenous infusion over 30 minutes on Day -6 to Day -2.
DRUG	Cyclophosphamide	1. Low dose pre-transplant cyclophosphamide will be administered intravenously (IV) over 1- 2 hours, (depending on volume) on Days -6 and -5. The dose of pre-transplant cyclophosphamide is 14.5 mg/kg/day. 2. High dose cyclophosphamide \[50mg/kg (Ideal Body Weight)\] will be administered on Day 3 post-transplant (within 60 to 72 hours of marrow infusion) and on Day 4 post-transplant. Cyclophosphamide will be given IV over 1-2 hours depending on volume.
RADIATION	Total Body Irradiation	Total body irradiation, consisting of 200 centigray (cGy) Anterior-Posterior/Posterior-Anterior (AP/PA) with 4 Megavolts (MV) or 6 MV photons at 8-12 cGy/min at the point of prescription will be administered in a single day on Day -1.
DRUG	acetaminophen	650 mg orally prior to antithymocyte globulin infusion.
DRUG	diphenhydramine	25mg diphenhydramine orally prior to antithymocyte globulin infusion.
DRUG	methylprednisolone	On Days -9 to -7 methylprednisolone 1mg/kg IV 1 hour prior ATG. This dose may be repeated once 3 hours after the first dose of steroids. On Day -6 and -5, methylprednisolone 0.75 mg/kg/ IV as a single dose; on Days -4 and -3, methylprednisolone 0.5 mg/kg/ IV as a single dose; on Day -2 methylprednisolone 0.25 mg/kg/ IV as a single dose.
BIOLOGICAL	bone marrow transplant	Unprocessed, unmanipulated bone marrow will be harvested from the donor and infused into the recipient on Day 0.
DRUG	MESNA	A series of MESNA doses will be administered for each dose of high dose, post-transplant cyclophosphamide. The total daily dose of MESNA is equal to 80% of the total daily dose of cyclophosphamide.
DRUG	mycophenolate mofetil	MMF will be administered at a dose of 15 mg/kg orally three times per day based upon actual body weight, with the maximum of 3 grams a day from Day 5 to 35. The dose will then be reduced to the standard 1 g twice daily thereafter.
DRUG	prednisone	Prednisone will be administered at a dose of 10 mg orally daily from Day 5 for 12 weeks. Thereafter the dose will be reduced to 5 mg orally daily.
DRUG	filgrastim	All recipients will receive 5 microgram/kg per day of filgrastim as a single, subcutaneous injection from Day 5 post-transplant until the absolute neutrophil count is greater than 1000/µl on three consecutive measurements over at least 2 days.

Timeline

• Start date: 2014-01-07
• Primary completion: 2017-09-06
• Completion: 2017-09-06
• First posted: 2014-01-08
• Last updated: 2018-09-24
• Results posted: 2018-09-19

Locations

1 site across 1 country: United States