Cellular Immunotherapy in Recipients of Human Leukocyte Antigen (HLA)-Mismatched, Living Donor Kidney Transplants

NCT ID: NCT03605654

Last Updated: 2024-06-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-31
• Study Completion Date: 2026-10-31

Brief Summary

The Phase 2 primary objective is to evaluate achievement of persistent mixed chimerism and withdrawal of at least one immunosuppression drug for a minimum of 6 months with no episodes of biopsy-proven acute rejection or transplant kidney loss induced by cellular immunotherapy with MDR-102 in recipients of 1, 2, or 3 out of 6 human leukocyte antigen (HLA)-mismatched, living donor kidney transplants.

The Phase 3 primary objective is to evaluate achievement of induction of immune quiescence by cellular immunotherapy with MDR-102 in recipients of 1, 2, or 3 out of 6 HLA-mismatched, living donor kidney transplants. Immune quiescence is defined as remaining on maintenance immunosuppression monotherapy with Tac or CsA for 12 months or more after completion of anti-rejection immunosuppression drug therapy reduction with no episodes of biopsy-proven acute rejection, transplant kidney loss, or subject deat.

Detailed Description

Currently, patients receiving a transplanted kidney are required to take life-long immunosuppressive medications to prevent rejection of the transplanted kidney. These medications carry substantial side effects. In addition, these medicines often do not completely control damage to the kidney from the recipients' immune system, ultimately causing the kidney to fail.

Medeor Therapeutics is developing a novel cell-based therapy as personalized cellular immunotherapies to improve outcomes in organ transplant recipients.

The purpose of the current Phase 2/3 study is to demonstrate the efficacy and safety of MDR-102 for the induction of immune quiescence in a prospective, randomized, open-label, multi-center clinical trial. MDR-102 is intended to induce mixed lymphohematopoietic chimerism and donor specific immune quiescence in order to preserve transplant kidney function, avert transplant kidney rejection, and reduce the cumulative and serious side effects associated with immunosuppression drugs.

Conditions

Kidney Transplant Rejection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Investigational Arm

A low-dose Total Lymphoid Irradiation and anti- thymocyte globulin combined with a single infusion of MDR-102 post-kidney transplant and standard anti-rejection medications in recipients of 1, 2, or 3 out of 6 human leukocyte antigen (HLA)-mismatched, living donor kidney transplants

Group Type: EXPERIMENTAL

MDR-102

Intervention Type: BIOLOGICAL

Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells

Active Control Arm

Standard anti-rejection medications that would be given to kidney transplant recipients who are outside the study

Group Type: ACTIVE_COMPARATOR

Immunosuppressive Agents

Intervention Type: DRUG

Standard Anti-Rejection Medications that would be given to kidney transplant recipients who are outside the study

Non-Randomized Exploratory Arm

A low-dose Total Lymphoid Irradiation and anti- thymocyte globulin combined with a single infusion of MDR-102 post-kidney transplant and standard anti-rejection medications in recipients of 4, 5, or 6 out of 6 human leukocyte antigen (HLA)-mismatched, living donor kidney transplants

Group Type: EXPERIMENTAL

MDR-102

Intervention Type: BIOLOGICAL

Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells

Interventions

MDR-102

Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells

Intervention Type: BIOLOGICAL

Immunosuppressive Agents

Standard Anti-Rejection Medications that would be given to kidney transplant recipients who are outside the study

Intervention Type: DRUG

Other Intervention Names

Corticosteroids; Mycophenolate Mofetil; Tacrolimus

Eligibility Criteria

Inclusion Criteria

• Planned recipient of a first kidney allograft from an human leukocyte antigen (HLA)-matched, living related donor. Zero-mismatch transplants are excluded
• Age ≥18 and ≤65 years
• Single solid organ recipient (kidney only)
• ABO compatibility with donor

• Human leukocyte antigen (HLA)-mismatched first degree (parent, child or sibling) or second-degree (child of a sibling) relative of the prospective recipient participant. Zero-mismatch transplants are excluded
• Age ≥18 and ≤65 years
• Prepared to be a living related kidney donor, and capable of undergoing granulocyte-colony stimulating factor (G-CSF) mobilization and apheresis of hematopoietic cells

Exclusion Criteria

• Underlying kidney disease with a high risk of disease recurrence in the transplanted kidney
• Baseline positive donor-specific anti-HLA antibody testing
• Is taking immunosuppressive therapy
• Prior hematopoietic cell transplant, organ transplant, any cell therapy, or any gene therapy
• Evidence of prior hepatitis B (HBV) or hepatitis C (HCV)

• History of autoimmune disorders
• History of type 1 or type 2 diabetes mellitus
• Tests confirmed positive for human immunodeficiency virus (HIV), HBV, HCV
• History of infection with Zika virus

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medeor Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lenuta Micsa, MD

Role: STUDY_DIRECTOR

Medeor Therapeutics

Other Identifiers

MDR-102-mMLK

Identifier Type: -

Identifier Source: org_study_id