Sequential, Related Donor Partial Liver Transplantation Followed by Bone Marrow Transplantation for Hepatocellular Carcinoma (HCC)
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|ClinicalTrials.gov Identifier: NCT02702960|
Recruitment Status : Active, not recruiting
First Posted : March 9, 2016
Last Update Posted : February 2, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Fibrolamellar Hepatocellular Carcinoma Hepatocellular Carcinoma (Fibrolamellar Variant) Hepatocellular Carcinoma||Procedure: living related donor partial liver transplantation Radiation: Total body irradiation Procedure: Bone marrow transplant from same donor Drug: Cyclophosphamide Drug: Mesna Drug: Filgrastim Drug: Tacrolimus Drug: mycophenolate mofetil Drug: Prednisone Drug: Antithymocyte globulin Drug: fludarabine||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Sequential, Related Donor Partial Liver Transplantation Followed by Bone Marrow Transplantation for Fibrolamellar or Non-fibrolamellar Hepatocellular Carcinoma (HCC) Including Fibrolamellar HCC|
|Study Start Date :||March 2016|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||January 2020|
Experimental: part. liver transplant and BMT
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.
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 wksRadiation: 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
Other Name: BMTDrug: 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
Other Name: CytoxanDrug: Mesna
administered on Days 3 and 4 with PTCy
Other Name: sodium-2-mercaptoethane sulfonateDrug: Filgrastim
administered daily starting on Day 5 until absolute neutrophil count (ANC) recoveryDrug: Tacrolimus
Given after liver transplant for through day -7, stopped on day -6 and restarted on day 5 post BMTDrug: mycophenolate mofetil
Given after liver transplant for through day -7, stopped on day -6 and restarted on day 5 post BMT
Other Name: MMFDrug: Prednisone
Given after liver transplant for through day -7, stopped on day -6 and restarted on day 5 post BMTDrug: Antithymocyte globulin
Given from Day -16 to Day -14 prior to bone marrow transplantation on day 0
Other Name: ATGDrug: fludarabine
fludarabine given from Days -6 to Day -2 before BMT
- 1 year disease-free survival (at 1 year after BMT) [ Time Frame: 1 year ]Disease-free is defined as the lack of radiographic evidence of recurrence by computed tomography or MRI.
- Occurrence of Graft versus Host Disease [ Time Frame: 1 year ]Determine the cumulative incidences of acute grades II-IV, III-IV and chronic graft-versus-host disease
- Death [ Time Frame: 1 year ]Proportion of transplanted participants who die
- Liver allograft failure [ Time Frame: 1 year ]Determine the proportion of transplanted participants with liver allograft rejection demonstrated by a biopsy or clinically if a biopsy cannot be performed.
- Efficacy measure - proportion disease free [ Time Frame: 1 year ]The proportion of transplanted participants who remain free of disease recurrence for 1 year post bone marrow transplantation
- Efficacy measure- proportion off immunosuppression without graft versus host disease (GVHD) or liver rejection [ Time Frame: 1 year ]The proportion of participants who are off immunosuppression without GVHD or liver rejection at 1 year after bone marrow transplantation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02702960
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21205|