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Patients receive living related donor partial liver transplantation performed according to standard practices. Patients will be maintained on tacrolimus, MMF, and prednisone after liver transplantation.

Upon recovery, patient must undergo eligibility screening for bone marrow transplantation (BMT).

If eligible, patients will begin:

Antithymocyte globulin (ATG): Day -16 to Day -14; fludarabine: Days -6 to Day -2 low-dose cyclophosphamide: Day -6 and -5. Tacrolimus, mycophenolate mofetil (MMF), and prednisone: day -7 and day -6. Total body irradiation on Day -1 Bone marrow infusion on Day 0. High dose cyclophosphamide plus MESNA: Day 3 and 4th Filgrastim, tacrolimus,MMF, and prednisone: Day 5 until neutrophil counts recover.

Patients followed up through post transplant day 60, then weekly following discharge.

HLA matched or haploidentical related living donor partial liver transplant followed by tacrolimus, prednisone, and MMF immunosuppression for \>3 wks

living related donor partial liver transplantation

200 cGy total body irradiation (TBI) on Day -1.

Total body irradiation

BMT using cells from the same Human Leukocyte Antigen (HLA)-matched or -haploidentical living related donor will be performed on Day 0

Bone marrow transplant from same donor

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

administered daily starting on Day 5 until absolute neutrophil count (ANC) recovery

Filgrastim

Given after liver transplant for through day -7, stopped on day -6 and restarted on day 5 post BMT

mycophenolate mofetil

Given from Day -16 to Day -14 prior to bone marrow transplantation on day 0

Antithymocyte globulin

fludarabine given from Days -6 to Day -2 before BMT

fludarabine

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.

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.

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

The proportion of transplanted participants who remain free of disease recurrence for 1 year post bone marrow transplantation

The proportion of participants who are off immunosuppression without GVHD or liver rejection at 1 year after bone marrow transplantation.

Disease-free is defined as the lack of radiographic evidence of recurrence by computed tomography or MRI.

Determine the cumulative incidences of acute grades II-IV, III-IV and chronic graft-versus-host disease

Proportion of transplanted participants who die

Determine the proportion of transplanted participants with liver allograft rejection demonstrated by a biopsy or clinically if a biopsy cannot be performed.

Fibrolamellar Cancer Foundation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

The LDLT will be performed by the UW Division of Transplantation in accordance with the standard of care for this operation.

Living Donor Liver Transplantation

David P Al-Adra, MD, PhD

This study will test the safety and efficacy of living donor liver transplant after standard-of-care chemotherapy for participants with non-resectable liver metastases (LM) from colorectal cancer. 25 donor-recipient pairs will be enrolled (50 participants). Donors will be on study for 2 years and recipients will be on study for up to 5 years.

This study is a single center, open-label study available to male and female adults with CRC LM that are deemed to be "unresectable" and who are receiving standard of care chemotherapy. Participants will be worked up for LDLT while continuing to receive chemotherapy and, if deemed eligible for surgery, will stop chemotherapy 4 weeks prior to receiving a living donor transplant. Recipients will be followed for 5 years (for safety, survival and disease recurrence for purposes of study data collection). They will continue to be monitored for safety, survival and disease recurrence indefinitely as part of University of Wisconsin (UW) Health's Organ Transplant Program care standards. Living liver donors will be followed for 2 years after transplant surgery for safety monitoring as part of this study.

Recruitment will be done in two stages. The first stage will be a pilot study of 5 recipients to determine if LDLT is a suitable treatment for patients with non-resectable LM. If, after 3 years of follow-up, the overall survival is greater than 60%, stage two recruitment will commence. Thus, an interim analysis will be done for the first 5 recipients prior to requiring a larger number of subjects. Stage two recruitment will focus on accruing a total of up to 20 additional recipients to be analyzed.

The control group will consist of any potential recipients that sign the informed consent and are enrolled in the study but do not undergo LDLT due to a lack of an eligible donor. These participants will be referred back to their medical oncologists to receive standard of care chemotherapy, and will continue to be followed as the control group.

Patients who sign the informed consent and are enrolled in the study with an eligible live donor but do not undergo LDLT due to disease progression or a contraindication is established for undergoing LT (exclusion criteria) will also be referred back to their medical oncologists to receive standard of care chemotherapy. This group will be followed as part of the intent to treat cohort.

single-center, open-label, two-stage recruitment

* pilot study of 5 recipients to determine if LDLT is a suitable treatment for patients with non-resectable LM with 3 years of follow-up, if Overall Survival greater than 60%, then
* stage two recruitment focusing on accruing additional recipients will commence.
* control group of participants that sign the informed consent and are enrolled in the study but do not undergo LDLT due to a lack of an eligible donor

Living Donor Liver Transplantation for CRC Liver Metastases

Neo-adjuvant Chemotherapy Plus Living Donor Liver Transplantation (LDLT) for Non-Resectable Liver Metastases From Colorectal Cancer (CRC)

Overall survival, defined as length of time from the start of (neoadjuvant) chemotherapy that subjects diagnosed with colorectal liver metastases are still alive.

DFS, defined as length of time after LDLT during which no disease is found according to RESIST v1.1 criteria.

Patterns of recurrence will be investigated, assessed by standard of care chest, abdominal and pelvis imaging.

Surviving number of recipients who receive LDLT vs. control subjects will be assessed at 1-, 3-, and 5-years.

Quality of life is measured at 1-, 3-, and 5-years using the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire). The questionnaire assesses multi-item scales, each item scoring from 1 to 4, with higher scores representing a higher level of symptomatology or problems.

Quality of life is measured at 1-, 3-, and 5-years using the EORTC QLQ-LMC21 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire). The questionnaire assesses multi-item scales, each item scoring from 1 to 4, with higher scores representing a higher level of symptomatology or problems.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sequential, Related Donor Partial Liver Transplantation Followed by Bone Marrow Transplantation for Hepatocellular Carcinoma (HCC)	NCT02702960	Fibrolamellar H... Hepatocellular ... Hepatocellular ...	living related ... Total body irra... Bone marrow tra... Cyclophosphamid... Mesna Filgrastim Tacrolimus mycophenolate m... Prednisone Antithymocyte g... fludarabine	16 Years - 65 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Living Donor Liver Transplantation for CRC Liver Metastases	NCT05175092	Liver Metastasi...	Living Donor Li...	18 Years - 65 Years	University of Wisconsin, Madison
Living Donor Liver Transplantation for CRC Liver Metastases	NCT05175092	Liver Metastasi...	Living Donor Li...	18 Years - 65 Years	University of Wisconsin, Madison

Spots Global Cancer Trial Database for living donor liver transplant