A Safety and Efficacy Study of FCR001 vs Standard of Care in de Novo Living Donor Kidney Transplantation


About this study

The purpose of this study is to assess the safety, effectiveness, and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Written informed consent must be obtained, from recipients and donors, before any assessment is performed on the respective subject.
  • Recipient age ≥ 18 years; Donor age ≥ 18 and ≤ 60 years.
  • Recipients of a first kidney transplant from a living unrelated or non-human leukocyte antigen (HLA) identical living related donor.
  • Donor willing to undergo mobilization, apheresis and 12-month safety follow-up p and meets all local standard eligibility criteria to donate stem cells for allogeneic transplantation.

Recipient and Donor Exclusion Criteria:

  • Recipient or donor with use of other investigational drugs within 30 days (or within 5 drug half-lives) of signing informed consent.
  • Recipient or donor with history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
  • Recipient and donor who are identical twins.
  • Recipient or donor who is a pregnant or nursing (lactating) woman.
  • Recipient or donor with history of malignancy or premalignant syndrome (e.g., myelodysplastic syndrome) of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
  • Recipient or donor with known bone marrow aplasia.

Recipient-only Exclusion Criteria:

  • Multi-organ or cell transplant recipient.
  • Panel reactive antibodies (calculated panel reactive antibody > 20% by Flow/Luminex).
  • Recipient is blood type ABO incompatible or has positive crossmatch (Flow/Luminex) vs. donor.
  • Presence of donor-specific antibodies (DSA) at any time pre-transplant.
  • Recipient who is human immunodeficiency virus (HIV) hepatitis B surface antigen (HBsAg) or hepatitis c virus (HCV) positive. Recipients with history of HCV infection may participate if there is a documented history of treatment with an antiHCV agent and either one (1) negative polymerase chain reaction (PCR) at least three (3) months after last dose of treatment, or two (2) negative PCRs at least 2 weeks apart over a maximum of 4 weeks.
  • Recipient with systemic infection, current or within the 2 weeks prior to conditioning; or history of recurrent infection (e.g., polycystic liver/kidney disease, unless native kidneys removed at time of transplant).
  • Recipient with any baseline condition requiring or anticipated will require chronic or intermittent use of systemic steroids or other IS (e.g., autoimmune disease, asthma) throughout the course of the study.
  • Recipient who had a live attenuated vaccine administered within 2 months of planned transplant surgery.
  • Recipient with a body mass index (BMI) < 18 or > 35 kg/m^2 .
  • Recipient requiring systemic anticoagulation; e.g., for hyper-coagulation disorders, deep vein thrombosis, atrial fibrillation, that cannot be temporarily interrupted which would preclude renal biopsy.
  • Recipient with contraindication to total body irradiation (TBI) according to local radiologist; e.g., previous radiation therapy at a dose which would preclude TBI, inadequate pulmonary function.
  • Recipient with autologous or allogeneic hematopoietic progenitor cell transplant prior to signing informed consent.
  • All recipient women of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, who do not agree to using highly effective methods of contraception during dosing of study treatment. For FCR-R WOCBP who have completely discontinued mycophenolate, contraception may be discontinued after Month 36 provided no mycophenolate is restarted. WOCBP assigned as FCR-D must maintain highly effective contraception from the time of assignment to FCR001 through 1 month after the end of the mobilization period. Highly effective contraception methods include:
    • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e,g,, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception;
    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) total hysterectomy or tubal ligation at least 6 weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;
    • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject;
    • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.

In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before entering study screening.

Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to study screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment if she considered not of childbearing potential.

  • Sexually active male CTR-R must use a condom during intercourse throughout the study and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of drugs via seminal fluid. For FCR-R this requirement may be lifted at 6 weeks after MMF and tacrolimus have been discontinued.

Donor-only Exclusion Criteria:

  • Biologically unrelated female donor transplant to male recipient.
  • Donor tested positive for Zika virus (ZIKV) infection. Zika infection is excluded by negative nucleic acid testing result on either serum or urine PLUS a negative Zika IgM. Only donors with the following risk factors must be tested:
    • Medical diagnosis of ZIKV in the past 6 months;
    • Residence in, or travel to, an area with an increased risk for ZIKV transmission within the past 6 months;
    • Sex within the past 6 months with a person who has either of the risk factors listed in items above.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Mark Stegall, M.D.

Contact us for the latest status

Contact information:

Nong Braaten L.P.N.

(507) 538-9617


Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Hasan Khamash, M.D.

Contact us for the latest status

Contact information:

Leena Abraham R.N.

(480) 342-6750


More information


  • Successful solid organ transplantation currently requires the life-long use of medications to suppress the immune system in order to prevent transplant rejection. Drug-based immunosuppression significantly increases the risk of infection and cancer, as well as being very costly. Development of new therapies to minimize or eliminate entirely the need for anti-rejection drugs is of great interest to the transplant community. Therapeutic cell transfer for the control of the human immune system represents a compelling approach to reduce or eliminate the need for anti-rejection drugs. Establishment of durable hematopoietic chimerism through hematopoietic stem cell transplantation (HSCT) has been shown in preclinical models and patients to lead to donor specific tolerance. However, the application HSCT is limited by the potential toxicity of conditioning regimens, the risk of graft versus host disease (GVHD) and the challenge of HLA mismatching. In this review we describe the clinical outcomes and science behind a CD8/TCR facilitating cell-based hematopoietic stem cell transplant approach (termed FCRx) to induce tolerance to mismatched renal allografts while minimizing the risk of graft-versus-host GVHD and achieving avoidance of long-term immunosuppressant drugs in living donor kidney transplant recipients. Read More on PubMed
  • Nineteen subjects have more than 18 months' follow-up in a phase IIb tolerance protocol in HLA-mismatched recipients of living donor kidney plus facilitating cell enriched hematopoietic stem cell allografts (FCRx). Reduced intensity conditioning preceded a kidney allograft, followed the next day by FCRx. Twelve have achieved stable donor chimerism and have been successfully taken off immunosuppression (IS). We prospectively evaluated immune reconstitution and immunocompetence. Return of CD4 and CD8 T central and effector memory cell populations was rapid. T-cell receptor (TCR) Excision Circle analysis showed a significant proportion of chimeric cells produced were being produced de novo. The TCR repertoires posttransplant in chimeric subjects were nearly as diverse as pretransplant donors and recipients, and were comparable to subjects with transient chimerism who underwent autologous reconstitution. Subjects with persistent chimerism developed few serious infections when off IS. The majority of infectious complications occurred while subjects were still on conventional IS. BK viruria and viremia resolved after cessation of IS and no tissue-invasive cytomegalovirus infections occurred. Notably, although 2 of 4 transiently or nonchimeric subjects experienced recurrence of their underlying autoimmune disorders, none of the chimeric subjects have, suggesting that self-tolerance is induced in addition to tolerance to alloantigen. No persistently chimeric subject has developed donor-specific antibody, and renal function has remained within normal limits. Patients were successfully vaccinated per The American Society for Blood and Marrow Transplantation guidelines without loss of chimerism or rejection. Memory for hepatitis vaccination persisted after transplantation. Chimeric subjects generated immune responses to pneumococcal vaccine. These data suggest that immune reconstitution and immunocompetence are maintained in persistently chimeric subjects. Read More on PubMed
  • We recently reported that durable chimerism can be safely established in mismatched kidney recipients through nonmyeloablative conditioning followed by infusion of a facilitating cell (FC)-based hematopoietic stem cell transplantation termed FCRx. Here we provide intermediate-term follow-up on this phase II trial. Read More on PubMed
  • New advances in achieving hematopoietic chimerism may facilitate immunological tolerance to kidney transplants. Read More on PubMed
  • The toxicity of chronic immunosuppressive agents required for organ transplant maintenance has prompted investigators to pursue approaches to induce immune tolerance. We developed an approach using a bioengineered mobilized cellular product enriched for hematopoietic stem cells (HSCs) and tolerogenic graft facilitating cells (FCs) combined with nonmyeloablative conditioning; this approach resulted in engraftment, durable chimerism, and tolerance induction in recipients with highly mismatched related and unrelated donors. Eight recipients of human leukocyte antigen (HLA)-mismatched kidney and FC/HSC transplants underwent conditioning with fludarabine, 200-centigray total body irradiation, and cyclophosphamide followed by posttransplant immunosuppression with tacrolimus and mycophenolate mofetil. Subjects ranged in age from 29 to 56 years. HLA match ranged from five of six loci with related donors to one of six loci with unrelated donors. The absolute neutrophil counts reached a nadir about 1 week after transplant, with recovery by 2 weeks. Multilineage chimerism at 1 month ranged from 6 to 100%. The conditioning was well tolerated, with outpatient management after postoperative day 2. Two subjects exhibited transient chimerism and were maintained on low-dose tacrolimus monotherapy. One subject developed viral sepsis 2 months after transplant and experienced renal artery thrombosis. Five subjects experienced durable chimerism, demonstrated immunocompetence and donor-specific tolerance by in vitro proliferative assays, and were successfully weaned off all immunosuppression 1 year after transplant. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients. Read More on PubMed

Study Results Summary

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