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Fibrolamellar Hepatocellular CarcinomaPhase 2NCT02702960

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

A Phase 2 study testing living related donor partial liver transplantation, Total body irradiation and Bone marrow transplant from same donor in people with Fibrolamellar Hepatocellular Carcinoma and Hepatocellular Carcinoma (Fibrolamellar Variant), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 to 65 years
What is being tested?
living related donor partial liver transplantation, Total body irradiation and Bone marrow transplant from same donor
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Mar 2016to 3 Jan 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • RECIPIENT
  • Histologic diagnosis of liver-confined fibrolamellar or non-fibrolamellar HCC. Ineligible for curative resection or deceased donor liver transplantation by virtue of NOT meeting the Milan criteria or down-staging criteria:
  • Single viable tumor ≤5 cm in size or ≤3 tumors each ≤3 cm in size based on CT or Magnetic resonance (MR) imaging
  • Pretransplant alpha fetoprotein (AFP) level of ≤400.
  • Available human leukocyte antigen (HLA)-matched or -haploidentical, living related donor who is willing to donate bone marrow and part of liver. The donor and recipient must be HLA identical for at least one allele (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C and HLA-DRB1. Fulfilment of this criterion shall be considered sufficient evidence that the donor and recipient share one HLA haplotype.
  • Age 16 to 65 years.
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  • Normal estimated left ventricular ejection fraction ( >30% ) and no history of ischemic heart disease requiring revascularization, unless cleared by a cardiologist (as per normal liver and bone marrow (BM) transplant eligibility requirements). Those with an ejection fraction between 30-40%, will require a cardiology consultation and clearance for transplantation.
  • Forced expiratory volume (FEV1) and forced vital capacity (FVC) > 40% of predicted at the screening visit.
  • Serum creatinine <2.0 mg/dl
  • For women of childbearing potential, a negative serum or urine pregnancy test with sensitivity less than 50 milli-International unit (mIU)/m within 72 hours before the start of study medication.
  • Use of two forms of contraception with less than a 5% failure rate or abstinence by all transplanted participants for 12 months after the first dose of study therapy. For the first 60 days post-transplant, recipients should be encouraged to use non-hormonal contraceptives due to the potential adverse effect of hormones on bone marrow engraftment.
  • Ability to receive oral medication.
  • Ability to understand and provide informed consent.
  • Must meet all other criteria for listing for liver transplantation
  • DONOR:
  • HLA-matched or -haploidentical, parent, child, sibling, or half-sibling of the recipient
  • Meets all requirements for live liver donation based on established criteria
  • Ability to understand and provide informed consent for all study procedures including partial liver transplant and bone marrow harvest.
  • Age < 60 years
  • Body Mass Index (BMI) <35

Who cannot join

  • RECIPIENT
  • Extrahepatic disease at the time of enrollment.
  • Macrovascular invasion by tumor as seen on imaging
  • Anti-donor HLA antibody with a level that produces a positive test on flow cytometric crossmatch. [Note: patients with a positive flow cytometric crossmatch may undergo desensitization and may become eligible, at the discretion of the protocol investigators, if desensitization decreases the antibody concentration to a level that produces a negative flow cytometric crossmatch.]
  • Ineligible for liver transplantation per institutional criteria (see Appendix 1)
  • Women who are breastfeeding.
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  • History of positive HIV-1 or HIV-2 serologies or nucleic acid test.
  • Active hepatitis B infection as documented by positive Hepatitis B assay
  • Any active, severe local or systemic infection at the screening visit.
  • Use of investigational drug, other than the study medications specified by the protocol, within 30 days of transplantation.
  • Receipt of a live vaccine within 30 days of receipt of study therapy.
  • The presence of any medical condition that the Investigator deems incompatible with participation in the trial.
  • DONOR
  • Age: less than age 18 or older than age 60
  • BMI >35
  • History of blood product donation to the recipient
  • Significant cardiovascular disease (per cardiology consultation)
  • Significant pulmonary disease (per pulmonology consultation)
  • Significant renal disease
  • History of diabetes mellitus
  • Ongoing malignancies
  • Severe local or systemic infection
  • Severe neurologic deficits
  • Active substance abuse
  • Untreatable/unstable psychiatric illness
  • History of positive HIV-1 or HIV-2 serology or nucleic acid test.
  • Evidence of prior hepatitis B infection as evaluated by hepatitis B surface antigen (HBsAg), total hepatitis B core antibody, and hepatitis B surface antibody (anti-HBsAb).
  • Positive HBV PCR
  • Positive anti-hepatitis C (HCV) antibodies and a positive serum HCV RNA PCR. All positive HCV antibody results must be assessed by an electroimmunoassay enzyme-linked immunosorbent assay (EIA) assay and confirmed by a quantitative serum HCV RNA assay. Participants with positive HCV antibodies but undetectable serum HCV RNA may be considered for eligibility. Participants with negative anti-HCV antibodies but unexplained liver enzyme abnormalities must undergo a quantitative serum RNA assay to rule out false negative HCV serologies.
  • Autoimmune disease requiring immunosuppressive drugs for maintenance.
  • The presence of any medical condition that the Investigator deems incompatible with participation in the trial.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21205

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
living related donor partial liver transplantation, Total body irradiation, Bone marrow transplant from same donor, Cyclophosphamide, Mesna
Keywords
FL-HCC, living donor liver transplant, HLA matched first degree relative, Milan Criteria, Ephraim Fuchs, Fibrolamellar Cancer Foundation, fibrolamellar, non-fibrolamellar
Medical subject headings
Fibrolamellar hepatocellular carcinoma, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • living related donor partial liver transplantationProcedure or surgery

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

  • Total body irradiationRadiation

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

  • Bone marrow transplant from same donorProcedure or surgery

    Also called BMT

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

  • CyclophosphamideDrug

    Also called Cytoxan

    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

  • MesnaDrug

    Also called sodium-2-mercaptoethane sulfonate

    administered on Days 3 and 4 with PTCy

  • FilgrastimDrug

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

  • TacrolimusDrug

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

  • mycophenolate mofetilDrug

    Also called MMF

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

  • PrednisoneDrug

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

  • Antithymocyte globulinDrug

    Also called ATG

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

  • fludarabineDrug

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

Study groups in NCT02702960
Study groupRoleWhat they receive
part. liver transplant and BMTExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1 year disease-free survival (at 1 year after BMT)

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

    Measured: 1 year

Secondary outcomes (3)

  1. Occurrence of Graft versus Host Disease

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

    Measured: 1 year

  2. Death

    Proportion of transplanted participants who die

    Measured: 1 year

  3. Liver allograft failure

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

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2016 (estimated)
  2. Study startMar 2016
  3. Primary completion3 Jan 2018
  4. Study completion3 Jan 2018

Why it stopped: This study was withdrawn due to lack of necessary resources from the liver transplant surgical group.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02702960
Sponsor's protocol ID
J15171
Other IDs
IRB00080373
Status last verified
Jun 2018
First submitted
26 Feb 2016
Last updated
15 Jun 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing living related donor partial liver transplantation, Total body irradiation and Bone marrow transplant from same donor in people with Fibrolamellar Hepatocellular Carcinoma and Hepatocellular Carcinoma (Fibrolamellar Variant), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 15 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1 year disease-free survival (at 1 year after BMT) (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02702960.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2018.

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