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

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.

Conditions

• Kidney Transplantation

Interventions

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.

Sponsors & Collaborators

• Immune Tolerance Network (ITN)

  collaborator NETWORK

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Lode Swinnen, MD · Johns Hopkins University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-01-07

Primary Completion

2017-09-06

Completion

2017-09-06

Countries

• United States

Study Locations