Delayed Tolerance Through Mixed Chimerism

NCT05900401 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2023P000486
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the safety and effectiveness of a bone marrow transplant after kidney transplant (from either a living or deceased donor). An investigational medication and other treatments will be given prior to and after the transplant to help protect the transplanted kidney from being attacked by the body's immune system

Conditions

Kidney Failure; Kidney Transplant; Complications; Chimera

Keywords

Tolerance; Transplant

Outcome Measures

Primary Outcomes (2)

• Incidence of transient mixed chimerism

  3 months

• Incidence of renal allograft tolerance

  2 years after immunosuppression withdrawal

Secondary Outcomes (8)

• Incidence of Participant Survival

  2 years after immunosuppression withdrawal

• Incidence of Graft Survival

  2 years after immunosuppression withdrawal

• Incidence of Chimeric Transition Syndrome

  3 months

• Incidence of Allograft Rejection

  2 years after immunosuppression withdrawal

• Incidence of DSA

  2 years after immunosuppression withdrawal

Study Arms (2)

Kidney and Stem Cell Recipients

EXPERIMENTAL

Months-Years after standard transplant, patients will undergo bone marrow transplant (either from prospective collection of stem cells from their living donor, or from bone marrow collected at the time of deceased donation)

Other: Bone Marrow Transplant; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Siplizumab

Kidney and Stem Cell Donors

EXPERIMENTAL

PBSC will be collected from the LD via leukapheresis 1-4 weeks before the scheduled HSCT. The donor will first undergo standard GCSF mobilization: GCSF (can be TBO-GCSF) dosed at 10 mcg/kg/d (rounded to nearest pre-filled syringe) administered subcutaneously daily for 5 consecutive days. On the 5th day, the donor will undergo standard large volume leukapheresis. The target yield will be 2-3 x 106 CD34+ cells / kg of actual recipient body weight. A maximum of 3 days of pheresis will be allowed. A minimum of 2 x 106 CD34+ cells / kg of actual recipient body weight will be required to proceed

Procedure: Peripheral Blood Stem Cell Collection

Interventions

Bone Marrow Transplant OTHER

Months-Years after standard transplant, patients will undergo bone marrow transplant (either from prospective collection of stem cells from their living donor, or from bone marrow collected at the time of deceased donation)

Kidney and Stem Cell Recipients

Peripheral Blood Stem Cell Collection PROCEDURE

PBSC will be collected from the LD via leukapheresis 1-4 weeks before the scheduled HSCT. The donor will first undergo standard GCSF mobilization: GCSF (can be TBO-GCSF) dosed at 10 mcg/kg/d (rounded to nearest pre-filled syringe) administered subcutaneously daily for 5 consecutive days. On the 5th day, the donor will undergo standard large volume leukapheresis. The target yield will be 2-3 x 106 CD34+ cells / kg of actual recipient body weight. A maximum of 3 days of pheresis will be allowed. A minimum of 2 x 106 CD34+ cells / kg of actual recipient body weight will be required to proceed.

Kidney and Stem Cell Donors

Fludarabine DRUG

Fludarabine 15 mg/m2/day on days -5 to -3 (3 doses)

Kidney and Stem Cell Recipients

Cyclophosphamide DRUG

Cyclophosphamide (CP) 30 mg/kg/day on days -5 and -4

Kidney and Stem Cell Recipients

Rituximab DRUG

Rituximab on study day -6

Kidney and Stem Cell Recipients

Siplizumab DRUG

Siplizumab (anti-CD2 mAb) on days, -2, -1, 0 and +1.

Kidney and Stem Cell Recipients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female 18-65 years of age.
• Kidney transplant recipients from either LD or DD, with cryo-preserved HSCs available, good renal function (GFR\>60 ml/min/1.73m2), normal current allograft biopsy, and no history of documented rejection episodes.
• First or second renal transplant.
• Use of FDA-approved methods of contraception (those with less than a 3% failure rate) by all recipients from the time that study treatment begins until 104 weeks (24 months) after renal transplantation. (For further information on FDA- approved methods of contraception, see https://www.fda.gov/media/150299/download
• Ability to understand and provide informed consent.
• Negative COVID-19 test during screening and two days prior to HSC transplantation (HSCT).
• Deceased Donor (DD)
• Male or female 18-70 years of age.
• Consent to donate vertebral bones is obtained from the donor family.
• HSCs are successfully cryopreserved and saved \>2X106/kg (CD34+ cells) of the recipient.
• Acceptable laboratory parameters (hematology in normal or near-normal range. Liver function \<2 times the upper limit of normal, and normal creatinine)
• Negative for viral infection with HbsAg, HIV, HCV, or HTLV-1
• Negative COVID-19 test at the time of HSC procurement.
• Living Donor (LD)
• Willingness to provide HSCs by leukapheresis or bone marrow aspiration.

You may not qualify if:

• ABO blood group-incompatible renal allograft.
• Evidence of anti-HLA antibody (donor specific with an MFI \>1000) as assessed by routine methodology (Luminex)
• Previous history of biopsy proven rejection.
• Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (\<100,000/mm3).
• Seropositivity for HIV-1, hepatitis B surface or core antigen, or hepatitis C virus (confirmed by hepatitis C virus RNA).
• Active infection
• Left ventricular ejection fraction \< 40% as determined by TTE or clinical evidence of heart failure.
• Forced expiratory volume FEV1 or DLCO \< 50% of predicted.
• Lactation or pregnancy.
• History of cancer (following the American Transplant Society Guidelines)
• Underlying renal disease etiology with high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis). Autoimmune diseases such as Lupus and Thrombotic Thrombocytopenic Purpura.
• Enrollment in other investigational drug studies within 30 days prior to enrollment.
• Abnormal (\>2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT), or any patients on chronic anticoagulation therapy.
• Allergy or sensitivity to any component of Siplizumab, fludarabine, CP, tacrolimus, MMF or rituximab.
• Any medical condition that the investigator deems incompatible with participation in the trial. This includes a history of alcohol abuse or illicit drug use/dependence.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Ossium Health, Inc.: collaborator
• ITB-Med LLC: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Bone Marrow Transplantation; fludarabine; Cyclophosphamide; Rituximab; siplizumab

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Tatsuo Kawai

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD -- Professor of Surgery, Harvard Medical School

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: June 12, 2023
• Study Start: October 1, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

US (1)