Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH

NCT04540380 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Tolerance SMC-MGH
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal is to investigate the safety of the conditioning regimen, and its ability to induce donor/recipient lymphohematopoietic chimerism without Chimerism Transition Syndrome (CTS), which may result in donor-specific unresponsiveness (tolerance) to the renal allograft in the absence of maintenance immunosuppression.

Conditions

Renal Failure

Outcome Measures

Primary Outcomes (3)

• Incidence of Transient Chimerism

  36 months after immunosuppression withdrawal

• Incidence of Chimerism Transition Syndrome

  36 months after immunosuppression withdrawal

• Incidence of tolerance induction

  36 months after immunosuppression withdrawal

Interventions

Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Siplizumab DRUG

Conditioning regimen .Patients will receive Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation and Thymoglobulin

Combined bone marrow and kidney transplant PROCEDURE

Recipients will receive a conditioning regimen that includes rituximab on study days -7 and -2, fludarabine 10mg/m2/day on days -6 to -3 (4 doses), cyclophosphamide (22.5mg/kg/day) on days -5 and -4, followed by local thymic irradiation (7 Gy) on day -1 and Siplizumabon days -1, 0, and +1. Combined kidney and bone marrow transplant will be performed on study day 0. Methylprednisolone will be started at 250 mg/day on day 0 and tapered to prednisone 20mg by day 10 after which it will be continued until day 20. Prophylaxis will be provided for hemorrhagic cystitis, PCP, fungal infection, CMV, and perioperative infection. All patients who require any blood transfusion will receive only leukocyte-depleted and irradiated blood products for a period of at least 52 weeks following transplantation. The proportion of patients successfully weaned off immunosuppression without chimerism transition syndrome (CTS) will be assessed.

Eligibility Criteria

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

You may qualify if:

• Male or female 18-65 years of age.
• Candidate for a living-donor renal allograft from an HLA mismatched donor
• Subjects with chronic kidney disease stage or ESRD who are treated with either hemodialysis or peritoneal dialysis.
• First transplant.
• Use of FDA-approved methods of contraception
• Ability to understand and provide informed consent.
• Negative COVID at screening and 2 days before procedure

You may not qualify if:

• ABO blood group-incompatible renal allograft.
• Participant with a (non DSA) PRA \> 20% within 6 months prior to transplant
• Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (\<100,000/mm3).
• Seropositivity for HIV-1, hepatitis B core antigen, or hepatitis C virus (confirmed by hepatitis C virus RNA); or positivity for hepatitis B surface antigen.
• 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 a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis).
• Prior dose-limiting radiation therapy
• Known genetic disease or family history that may result in greater sensitivity to the effects of irradiation, or a physical deformity that would preclude adequate shielding or appropriate dosing during the irradiation component of the conditioning regimen
• 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).
• Allergy or sensitivity to any component of Siplizumab, Fludarabine, Cyclophosphamide, tacrolimus, DMSO, MMF or rituximab.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Rituximab; fludarabine; Cyclophosphamide; siplizumab; Kidney Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Renal Replacement Therapy; Therapeutics; Organ Transplantation; Transplantation; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: September 7, 2020
• Study Start: September 1, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

US (1)