Inducing tolerance in kidney transplant patients through mixed chimerism
Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH
This study is testing a new treatment approach to see if it can help kidney transplant patients avoid long-term medications by making their bodies accept the new kidney better.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Massachusetts General Hospital Academic / other |
| Drugs / interventions | Siplizumab, rituximab, radiation, Cyclophosphamide, Fludarabine |
| Locations | 1 site (Boston, Massachusetts) |
| Trial ID | NCT04540380 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety of a conditioning regimen designed to induce donor/recipient lymphohematopoietic chimerism, which may lead to donor-specific unresponsiveness to renal allografts without the need for ongoing immunosuppression. The approach involves administering a combination of Rituximab, Fludarabine, Cyclophosphamide, Thymic irradiation, and Siplizumab, alongside a combined bone marrow and kidney transplant. The study focuses on patients with chronic kidney disease or end-stage renal disease who are candidates for a living-donor renal transplant from an HLA mismatched donor.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18-65 who are undergoing their first living-donor renal transplant from an HLA mismatched donor.
Not a fit: Patients with ABO blood group incompatibility or significant comorbidities such as active infections or severe heart failure may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly reduce the need for lifelong immunosuppressive therapy in kidney transplant recipients.
How similar studies have performed: While the concept of mixed chimerism is promising, this specific approach is relatively novel and has not been extensively tested in prior studies.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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. * The presence of any medical condition that the investigator deems incompatible with participation in the trial. * Subjects who have non-insulin dependent diabetes (NIDDM) without good blood glucose control (HbA1c\<7). Subject with severe retinopathy, gastroparesis, or severe neuropathy which prevent subject's normal independent daily activities will be excluded from the study
Where this trial is running
Boston, Massachusetts
- Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
Study contacts
- Study coordinator: Tatsuo Kawai, MD PhD
- Email: tkawai@mgh.harvard.edu
- Phone: 617-726-0289
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.