NCT02702960

Sequential, Related Donor Partial Liver Transplantation Followed by Bone Marrow Transplantation for Hepatocellular Carcinoma (HCC)

Sequential, Related Donor Partial Liver Transplantation Followed by Bone Marrow Transplantation for Fibrolamellar or Non-fibrolamellar Hepatocellular Carcinoma (HCC) Including Fibrolamellar HCC

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 16 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This trial is a phase II, single arm, open-label, single center study to assess a reduced-intensity conditioning regimen, bone marrow transplantation and high dose PTCy in recipients of a partial liver allograft from a Human Leukocyte Antigen (HLA)-matched or -haploidentical living related donor in patients with HCC. The primary objective of this trial is to characterize recurrence-free survival at 1 year following bone marrow transplantation among recipients of prior partial liver transplantation from the same donor.

Detailed description

The purpose of this study is to characterize the safety and anti-tumor efficacy of sequential partial liver transplantation followed by bone marrow transplantation from the same living related donor. This treatment applies to patients whose cancer remains confined to the liver but is too widespread to be removed by surgery or treated by a liver transplant from a deceased donor. The purpose of this combined treatment is to reduce the risk of the cancer coming back after the liver transplant The bone marrow transplant may reduce the risk of cancer relapse in two ways. First, patients who have combined bone marrow and solid organ transplants may be able to get off all anti-rejection drugs, which inhibit the immune system from destroying cancer cells. Second, the donor's bone marrow contains cells of the immune system, which can attack any cancer cells that remain after the liver transplant. This trial is a phase II, single arm, open-label, single center pilot study to assess a reduced-intensity conditioning regimen, bone marrow transplantation and high dose post-transplantation cyclophosphamide (PTCy) in recipients of a partial liver allograft from a Human Leukocyte Antigen (HLA)-matched or -haploidentical living related donor in patients with HCC. The trial includes analyses of tumor characteristics and the number and phenotype of tumor infiltrating lymphocytes in the explanted tumor. The trial also includes periodic monitoring of circulating hepatocytes to correlate with tumor response. The study is expected to take two years to complete accrual of six patients, and the primary objective of this trial is to characterize recurrence-free survival at 1 year following bone marrow transplantation among recipients of prior partial liver transplantation from the same donor. Secondary objectives include documenting percentage of patients who become tolerant of the transplanted liver, i.e. off immunosuppression for \>6 months without biochemical evidence of liver rejection, and characterizing the relationship between donor chimerism and transplantation tolerance.

Conditions

• Fibrolamellar Hepatocellular Carcinoma
• Hepatocellular Carcinoma (Fibrolamellar Variant)
• Hepatocellular Carcinoma

Interventions

Type	Name	Description
PROCEDURE	living related donor partial liver transplantation	HLA matched or haploidentical related living donor partial liver transplant followed by tacrolimus, prednisone, and MMF immunosuppression for \>3 wks
RADIATION	Total body irradiation	200 cGy total body irradiation (TBI) on Day -1.
PROCEDURE	Bone marrow transplant from same donor	BMT using cells from the same Human Leukocyte Antigen (HLA)-matched or -haploidentical living related donor will be performed on Day 0
DRUG	Cyclophosphamide	Pre-transplantation low dose cyclophosphamide given day -6 and -5 Post-transplantation high dose cyclophosphamide (PTCy; 50 mg/kg/day) will be administered on Days 3 and 4 with hydration
DRUG	Mesna	administered on Days 3 and 4 with PTCy
DRUG	Filgrastim	administered daily starting on Day 5 until absolute neutrophil count (ANC) recovery
DRUG	Tacrolimus	Given after liver transplant for through day -7, stopped on day -6 and restarted on day 5 post BMT
DRUG	mycophenolate mofetil	Given after liver transplant for through day -7, stopped on day -6 and restarted on day 5 post BMT
DRUG	Prednisone	Given after liver transplant for through day -7, stopped on day -6 and restarted on day 5 post BMT
DRUG	Antithymocyte globulin	Given from Day -16 to Day -14 prior to bone marrow transplantation on day 0
DRUG	fludarabine	fludarabine given from Days -6 to Day -2 before BMT

Timeline

• Start date: 2016-03-01
• Primary completion: 2018-01-03
• Completion: 2018-01-03
• First posted: 2016-03-09
• Last updated: 2018-06-15

Locations

1 site across 1 country: United States