Study of Combined Kidney and Blood Stem Cell Transplant From a Brother or Sister Donor

NCT03707262 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HLA-Match Tolerance
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if an investigational treatment will allow kidney transplant recipients to better accept their new kidney and stop immunosuppressive medicines. This study is for kidney transplant recipients who receive a kidney from a sibling donor. The investigational treatment is started after kidney transplant. It begins with a regimen of a drug called rabbit anti-thymocyte globulin (rATG) combined with radiation therapy (known as total lymphoid irradiation, or TLI) to the lymph nodes and spleen. This is followed by an infusion of blood stem cells, which will be donated by the same sibling who donated their kidney. Researchers think that this treatment allows immune cells from the donor and recipient to live side by side, a condition referred to as "mixed chimerism." Mixed chimerism may help create a state of "tolerance" in kidney transplant recipients in which all immunosuppressive medications can be stopped without rejection of the transplanted kidney. This study will test whether (1) the investigational treatment will allow patients to stop immunosuppressive medications after their kidney transplant and (2) if the treatment impacts the rate of kidney rejection and the side effects of immunosuppressive medications.

Conditions

Renal Transplant Rejection; Tolerance; Kidney Transplant

Keywords

Tolerance; Kidney Transplant

Outcome Measures

Primary Outcomes (1)

• Withdrawal from immunosuppressive drugs

  Percentage of subjects free from all immunosuppressive drugs at 12 months after kidney transplantation.

  12 months post-kidney transplant

Secondary Outcomes (6)

• Graft rejection

  48 months post-kidney transplant

• Time to graft rejection

  48 months post-kidney transplant

• Graft failure

  48 months post-kidney transplant

• Time to graft failure

  48 months post-kidney transplant

• Survival

  12, 24, 36, and 48 months post-kidney transplant

Study Arms (1)

Donor CD34+ and CD3+ cell infusion

EXPERIMENTAL

The investigational products are (1) an intravenous infusion of granulocyte colony-stimulating factor (GCSF)-mobilized, Miltenyi-enriched CD34+ cells (≥ 5 million cells per kilogram) followed by (2) an infusion of CD3+ cells (5 million cells per kilogram) from an HLA-identical sibling living donor. The cells are infused around Day 11 post-transplant after the following pre-conditioning regimen: 1. 5 doses of rATG (1.5 mg/kg IV per day for 5 days, starting on the day of transplant) 2. 10 doses of TLI (120 centigray \[cGY\] x 10 fractions, starting the day after transplant)

Biological: Donor CD34+ and CD3+ cells

Interventions

Donor CD34+ and CD3+ cells BIOLOGICAL

Infusion of GCSF-mobilized, Miltenyi-enriched CD34+ hematopoietic stem/progenitor cells (HSPCs) (≥ 5 million cells/kg) and CD3+ cells (5 million cells/kg) from an HLA-identical sibling living donor, following pre-conditioning regimen of rATG and TLI.

Donor CD34+ and CD3+ cell infusion

Eligibility Criteria

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

You may qualify if:

• Males and females ages 18 years and older receiving living donor kidney transplant from an HLA-identical sibling at UCLA Medical Center.
• Agrees to participate in the study and is able to give informed consent.
• Resides or is willing to stay within 3 hours distance from UCLA Medical Center by ground transportation for the first three to six months of the trial at the physician's discretion.
• Meets institutional criteria for kidney and HSPC transplant.
• No known contraindication to administration of rATG or radiation.
• If patient is a female of reproductive potential (i.e., no documented absence of ovaries or uterus, history of tubal ligation, or post-menopausal status) patient must be confirmed not pregnant by a serum or urine pregnancy test) and must agree to practice a reliable form of contraception including hormonal treatments, barrier methods or intrauterine device for at least 12 months post-transplant. Karnofsky Performance Score ≥ 70.
• Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
• Adequate pulmonary function defined as FVC and DLCO of greater than or equal to 50% of predicted.
• Adequate liver function defined as total bilirubin ≤ 1.5 times the upper limit of normal and AST/ALT ≤ 2.0 times the upper limit of normal.
• Adequate social support based on evaluation by the UCLA renal transplant team licensed clinical social worker.

You may not qualify if:

• Donor is identical twin.
• ABO incompatibility with donor.
• Previous solid organ transplant
• Multi-organ transplantation
• Previous treatment with rATG or a known allergy to rabbit proteins
• History of active malignancy within the past 5 years with the exception of non-melanomatous skin cancer.
• a. History of another primary malignancy except for: i. Malignancy treated with curative intent and with no known active disease \>2 years before the first dose of study treatment and of low potential risk for recurrence ii. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease iii. Very low risk and low risk cancer adequately treated or on active surveillance b. Adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ, and DCIS)
• Pregnant (confirmed by urine or serum pregnancy test) or lactating.
• Leukopenia (with a white blood cell count \< 3,000/ µL) or thrombocytopenia (with a platelet count \< 100,000/ µL).
• Active bacterial, fungal, mycobacterial or viral infection (including active hepatitis B and/or C).
• Positive HLA DSA
• Seropositivity for HIV 1, HIV 2, HTLVI, HTLV II
• Active West Nile Virus infection
• Renal disease with high risk of recurrence (i.e., focal segmental glomerulosclerosis).
• Advanced hepatic fibrosis or cirrhosis secondary to hepatitis B and/or C diagnosis.

Sponsors & Collaborators

• Jeffrey Veale, MD: lead
• OneLegacy Foundation: collaborator

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Study Officials

• Jeffrey Veale, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruth Wynne Jones

CONTACT

424-402-9564; rwynnejones@mednet.ucla.edu

Jenny Lester

CONTACT

310-794-9728; jlester@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, David Geffen School of Medicine

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: October 16, 2018
• Study Start: November 6, 2019
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

US (1)