Kidney and Hematopoietic Cell Transplants Using a Regimen to Promote Hematopoietic Cell Engraftment

NCT04571203 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 1 other identifier: 57511
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm phase 1 non randomized dose finding study for safety, feasibility and efficacy of deceased donor vertebral body (VB) marrow cell infusion and kidney transplantation.

Conditions

Immune Tolerance

Outcome Measures

Primary Outcomes (2)

• Number of patients out of the total patients enrolled who received both the kidney and the bone marrow from the same donor.

  6 months

• Determine the dose of TBI that will support donor CD3 Tcell chimerism between 30-75% at 45 days post infusion

  TBI dose in cGy associated with donor Tcell chimerism of \>30 % immunosuppressive drug monotherapy.

  day 45

Secondary Outcomes (7)

• Number of patients who develop GVHD, all grades and types, within 60 months of kidney transplant

  60 months

• Number of patients with either bacterial, viral or fungal infection within 12 months post transplant .

  12 months

• Serum Creatinine

  up to 60 months

• Panel-Reactive Antibody (PRA)

  Baseline, month 9, and month 12

• Donor-Specific Antibody (DSA)

  Baseline, month 9, and month 12

Study Arms (1)

Phase I Study of Combined DD Kidney and HCT Transplant

EXPERIMENTAL

Single arm Phase 1 non randomized dose finding study for safety, feasibility and efficacy of deceased donor vertebral body (VB) marrow cell infusion

Biological: Combined Deceased Donor Kidney and Hematopoietic Cell Transplants

Interventions

Combined Deceased Donor Kidney and Hematopoietic Cell Transplants BIOLOGICAL

This combined kidney and hematopoietic cell transplants with a conditioning regimen with irradiation and ATG creates an environment of immune-tolerance. This promotes hematopoietic cell engraftment.

Also known as: Radiation

Phase I Study of Combined DD Kidney and HCT Transplant

Eligibility Criteria

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

You may qualify if:

• Patient is ≥ 18 years old, and \<65 years of age.
• Has End Stage Renal Disease (ESRD) and is a de novo kidney transplant candidate part Stanford standard of care.
• Listed with the Organ Procurement and Transplantation Network (OPTN) for deceased donor transplantation.
• A serotypic (Human Leucocyte Antigen) HLA match with the donor of a least 1 locus in A, B or DR.
• Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 1 year post transplant.
• Females have a negative serum pregnancy test.
• Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.
• No known contraindication to administration of rabbit ATG or low dose irradiation.
• Brain dead donor aged ≥ 16 and ≤ 55
• Organ Procurement Organization (OPO) consent for vertebral body procurement
• Organ Procurement Organization consent for research
• Projected cold ischemia time \<24 hours.

You may not qualify if:

• Known allergy to rabbit protein.
• History of malignancy with the exception of non melanoma skin malignancy.
• Pregnant woman or nursing mother.
• Body weight \>90kg or BMI \>35.
• Evidence of HIV 1/2 antibody (Ab), HTLV 1 and HTLV 2 Ab (Human T-Lymphotropic Virus), Hepatitis B sAg (surface antigen), Hepatitis C Ab, or positive syphilis screen.
• EBV (Epstein Bar Virus)Ab positive donor to EBV Ab negative recipient.
• Active bacterial, viral or fungal infection defined as currently taking medication for the infection.
• Leukopenia (white blood cell count \< 3000/mm3) or thrombocytopenia (with a platelet count \< 100,000/mm3).
• Psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the Stanford Transplant team caring for this potential patient would place the patient at an unacceptable risk.
• Concern for alcohol or other substance abuse.
• Kidney disease at high risk for post transplant recurrence: aHUS (atypical hemolytic- uremic syndrome) and C3 glomerulopathy
• Panel reactive antibody (PRA) \>80%.
• Positive donor specific antibody (DSA).
• Prior or combined organ transplant.
• Patients with \>5 pack year smoking history, smoking within 10 years of enrollment, or first degree relative with lung cancer.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94305, United States

Location

Related Publications (1)

• Busque S, Scandling JD, Lowsky R, Shizuru J, Jensen K, Waters J, Wu HH, Sheehan K, Shori A, Choi O, Pham T, Fernandez Vina MA, Hoppe R, Tamaresis J, Lavori P, Engleman EG, Meyer E, Strober S. Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal. Sci Transl Med. 2020 Jan 29;12(528):eaax8863. doi: 10.1126/scitranslmed.aax8863.

  PMID: 31996467 BACKGROUND

MeSH Terms

Interventions

Radiation

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• Robert Lowsky, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Stephan Busque, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery

Model Details: End Stage Renal Disease subjects will receive a deceased donor kidney and vertebral body stem cell infusion. These transplant recipients post kidney transplant will undergo conditioning by ATG, Total Lymphoid irradiation and 1 single dose of TBI. Subsequently, the vertebral body stem cell infusion will be administered.

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 30, 2020
• Study Start: May 6, 2022
• Primary Completion: October 1, 2025
• Study Completion (Estimated): October 1, 2029
• Last Updated: May 11, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)