RECRUITING

Vascularized Composite Bladder Allograft Transplantation

Conditions

Neurogenic Bladder Bladder Dysfunction Immunosuppression vascularized composite allograft

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase 0 trial tests the feasibility, functionality, and sustainability of vascularized composite bladder allograft transplantation in treating patients with terminal bladder pathology. A vascularized bladder allograft transplantation may provide a more durable and better-tolerated alternative to standard urinary diversion, which employs bowel. A robotic surgical approach will be employed.

Official Title

Robotic Vascularized Composite Bladder Allograft Transplantation: A Phase 0 (First-in-Human), Single Institutional Study for Deceased-Donor Bladder Transplantation

Quick Facts

Study Start:2023-05-01

Study Completion:2026-05-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05462561

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age 18-65 years. * Positive history of one of the following: * Bladder pathology resulting in poor compliance, recurrent infections, and/or resultant upper tract (kidney and ureteral) pathology, demonstrated by hydronephrosis with resultant kidney disease. * Localized, non-metastatic, muscle-invasive or lesser urothelial cell carcinoma of the bladder that requires therapeutic radical cystectomy will be considered only if the patient is already on pre-existing immunosuppression or who are expected candidates for immunosuppression in the near future, and then on a case-by-case basis after thorough evaluation and presentation to institutional tumor board committee. A minority of accrued patients are expected to have bladder cancer as the etiology of their cystectomy. * Patients that are on pre-existing immunosuppression will be included in this study. * Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regime. * Patients must demonstrate appropriate manual dexterity or sufficient assistance at home to perform clean intermittent catheterizations as needed. The patient (or assistant) must demonstrate proficiency in performing clean intermittent catheterization during pre-transplant workup. * No co-existing medical condition which, in the opinion of the study team, could affect the immunomodulatory protocol, surgical procedure, or functional results (see Exclusion Criteria below). If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of genitourinary transplantation. Examples of such medical conditions would include a burden of atherosclerotic disease that would preclude vascular anastomosis, and psychiatric disorders that would preclude reliable adherence to medications. * No active co-existing psychosocial problems (i.e., alcoholism, drug abuse). * Negative crossmatch with donor. * DONOR: Any potential brain dead donor considered for solid organ transplant. * DONOR: Age 18-65 years. * DONOR: Stable, meaning no requirement of excessive vasopressors for maintaining blood pressure. * DONOR: ABO compatibility. * DONOR: Negative cross-match with recipient.	* Positive history of one of the following medical co-morbidities: * Human immunodeficiency virus \[HIV\] (active or seropositive), active hepatitis B or C, viral encephalitis, untreated sepsis, active tuberculosis, viral encephalitis, toxoplasmosis, varicella zoster virus. * Conditions that may impact the success of the surgical procedure or increase the risk of postoperative complications including inherited coagulopathies like hemophilia, Von-Willebrand's disease, protein C and S deficiency, thrombocythemia, thallassemia, sickle cell disease. * Mixed connective tissue diseases and collagen disorders (can result in poor wound healing after surgery), including: * Mixed connective tissue disorder * Severe deforming rheumatoid arthritis * Infectious, post-infectious, or inflammatory (axonal or demyelinating) neuropathy * Ehler-Danlos syndrome * Lipopolysaccharidosis or amyloidosis (effects nerve regeneration). * Impaired liver function as evaluate by liver function panel, including the presence of hyperbilirubinemia, elevated aspartate aminotransferase/ alanine aminotransferase (AST/ALT), and the presence of secondary coagulopathy, measured by prothrombin, international normalized ratio, and partial thromboplastin time. * Severe anemia (hemoglobin \< 7 g/dL), leukopenia (WBC \< 3 x 10 \^ 9 cell/L), or thrombocytopenia (platelets \< 20 x10 \^ 9 cells/L). * Oncology patient specific: * History of any non-urothelial malignancy within the past 5 years, with the exception of non-melanomatous skin cancer and very-low to low risk prostate cancer on active surveillance. * History of metastasic malignancy within the past 5 years. * History of urothelial carcinoma in patients without pre-existing conditions that require immunosuppression and/or without the expected need for immunosuppression in the future. * Sensitized recipients; panel reactive antibody (PRA) \< 80%, with negative crossmatch to donor and no evidence of donor-specific antibody at time of transplant. * Patients unable to receive adequate follow-up care and/or unable to receive immunosuppression due to geographic, financial or other reasons. * Patients with a smoking history who cannot demonstrate smoking cessation for a period of 6 months prior to listing and a desire to abstain from post-operative smoking will be excluded. * Records of poor medical compliance, documented psychological disorder(s), substance abuse or incomplete psychological clearance. * Particular attention will be paid to the candidate's compliance and their desire to undergo the offered procedure. While there is no "score" on any particular evaluation that would rule out a patient, certain factors can aid in the identification of patients who for example may not have the ability to comply with the medical directives necessary to care for a genitourinary transplant, or psychologically are not prepared for transplant, or who have unrealistic expectations about the transplant. The decision on eligibility is a team decision. All members of the team will discuss each candidate in a multidisciplinary meeting and reasons for concern over eligibility will be discussed at a Selection Committee Meeting (per University of Southern California Transplant Center Policy). In circumstances where the candidate is considered to be less suitable, they could be given an opportunity to address these issues either through individual counseling or further education and then be reconsidered as a potential candidate. Every effort to prevent a request for allograft removal will be made. Towards these ends, a two-part initial psychiatric consultation will be rendered in addition to psychosocial evaluations already accounted for in the social work and transplantation evaluation prior to listing. The first visit focuses on background history and standard contraindications to transplantation, while the second visit is a more thorough discussion of the challenges ahead for the potential recipient and how these challenges relate to their strengths and vulnerabilities. If at this phase, or any subsequent one, significant psychological need emerges, the patient will be referred to another mental health professional for ongoing treatment with frequent communication between that provider and the transplant psychiatrist. The same psychiatrist responsible for listing and taking part in the protocol will not provide this treatment, given the potentially conflicting obligations involved and the disincentive present for the patient to be completely honest. If a greater than 6 month period of time elapses between listing and transplantation, a follow-up visit with psychiatry and social work will be arranged. * DONOR: Unresolved sepsis. * DONOR: Known history of urothelial or prostate cancer/malignancy. * DONOR: Known history of bladder or prostate surgery. * DONOR: Abnormal bladder capacity. * DONOR: Active sexually transmitted disease. * DONOR: Active cytomegalovirus (CMV), Epstein-Barr virus (EBV), or tuberculosis (TB) infections. * DONOR: Hepatitis B virus (HBV) core antibody, surface antigen, or DANN positive. * DONOR: Hepatitis C virus (HCV) antibody or viral load+. * DONOR: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS).

Inclusion Criteria

Exclusion Criteria

* Age 18-65 years.
* Positive history of one of the following:
* Bladder pathology resulting in poor compliance, recurrent infections, and/or resultant upper tract (kidney and ureteral) pathology, demonstrated by hydronephrosis with resultant kidney disease.
* Localized, non-metastatic, muscle-invasive or lesser urothelial cell carcinoma of the bladder that requires therapeutic radical cystectomy will be considered only if the patient is already on pre-existing immunosuppression or who are expected candidates for immunosuppression in the near future, and then on a case-by-case basis after thorough evaluation and presentation to institutional tumor board committee. A minority of accrued patients are expected to have bladder cancer as the etiology of their cystectomy.
* Patients that are on pre-existing immunosuppression will be included in this study.
* Patient agrees to comply with the protocol and states a dedication to the immunomodulatory treatment regime.
* Patients must demonstrate appropriate manual dexterity or sufficient assistance at home to perform clean intermittent catheterizations as needed. The patient (or assistant) must demonstrate proficiency in performing clean intermittent catheterization during pre-transplant workup.
* No co-existing medical condition which, in the opinion of the study team, could affect the immunomodulatory protocol, surgical procedure, or functional results (see Exclusion Criteria below). If the condition is amenable to treatment, the study team must agree that said condition should not significantly enhance the surgical risks of genitourinary transplantation. Examples of such medical conditions would include a burden of atherosclerotic disease that would preclude vascular anastomosis, and psychiatric disorders that would preclude reliable adherence to medications.
* No active co-existing psychosocial problems (i.e., alcoholism, drug abuse).
* Negative crossmatch with donor.
* DONOR: Any potential brain dead donor considered for solid organ transplant.
* DONOR: Age 18-65 years.
* DONOR: Stable, meaning no requirement of excessive vasopressors for maintaining blood pressure.
* DONOR: ABO compatibility.
* DONOR: Negative cross-match with recipient.

* Positive history of one of the following medical co-morbidities:
* Human immunodeficiency virus \[HIV\] (active or seropositive), active hepatitis B or C, viral encephalitis, untreated sepsis, active tuberculosis, viral encephalitis, toxoplasmosis, varicella zoster virus.
* Conditions that may impact the success of the surgical procedure or increase the risk of postoperative complications including inherited coagulopathies like hemophilia, Von-Willebrand's disease, protein C and S deficiency, thrombocythemia, thallassemia, sickle cell disease.
* Mixed connective tissue diseases and collagen disorders (can result in poor wound healing after surgery), including:
* Mixed connective tissue disorder
* Severe deforming rheumatoid arthritis
* Infectious, post-infectious, or inflammatory (axonal or demyelinating) neuropathy
* Ehler-Danlos syndrome
* Lipopolysaccharidosis or amyloidosis (effects nerve regeneration).
* Impaired liver function as evaluate by liver function panel, including the presence of hyperbilirubinemia, elevated aspartate aminotransferase/ alanine aminotransferase (AST/ALT), and the presence of secondary coagulopathy, measured by prothrombin, international normalized ratio, and partial thromboplastin time.
* Severe anemia (hemoglobin \< 7 g/dL), leukopenia (WBC \< 3 x 10 \^ 9 cell/L), or thrombocytopenia (platelets \< 20 x10 \^ 9 cells/L).
* Oncology patient specific:
* History of any non-urothelial malignancy within the past 5 years, with the exception of non-melanomatous skin cancer and very-low to low risk prostate cancer on active surveillance.
* History of metastasic malignancy within the past 5 years.
* History of urothelial carcinoma in patients without pre-existing conditions that require immunosuppression and/or without the expected need for immunosuppression in the future.
* Sensitized recipients; panel reactive antibody (PRA) \< 80%, with negative crossmatch to donor and no evidence of donor-specific antibody at time of transplant.
* Patients unable to receive adequate follow-up care and/or unable to receive immunosuppression due to geographic, financial or other reasons.
* Patients with a smoking history who cannot demonstrate smoking cessation for a period of 6 months prior to listing and a desire to abstain from post-operative smoking will be excluded.
* Records of poor medical compliance, documented psychological disorder(s), substance abuse or incomplete psychological clearance.
* Particular attention will be paid to the candidate's compliance and their desire to undergo the offered procedure. While there is no "score" on any particular evaluation that would rule out a patient, certain factors can aid in the identification of patients who for example may not have the ability to comply with the medical directives necessary to care for a genitourinary transplant, or psychologically are not prepared for transplant, or who have unrealistic expectations about the transplant. The decision on eligibility is a team decision. All members of the team will discuss each candidate in a multidisciplinary meeting and reasons for concern over eligibility will be discussed at a Selection Committee Meeting (per University of Southern California Transplant Center Policy). In circumstances where the candidate is considered to be less suitable, they could be given an opportunity to address these issues either through individual counseling or further education and then be reconsidered as a potential candidate. Every effort to prevent a request for allograft removal will be made. Towards these ends, a two-part initial psychiatric consultation will be rendered in addition to psychosocial evaluations already accounted for in the social work and transplantation evaluation prior to listing. The first visit focuses on background history and standard contraindications to transplantation, while the second visit is a more thorough discussion of the challenges ahead for the potential recipient and how these challenges relate to their strengths and vulnerabilities. If at this phase, or any subsequent one, significant psychological need emerges, the patient will be referred to another mental health professional for ongoing treatment with frequent communication between that provider and the transplant psychiatrist. The same psychiatrist responsible for listing and taking part in the protocol will not provide this treatment, given the potentially conflicting obligations involved and the disincentive present for the patient to be completely honest. If a greater than 6 month period of time elapses between listing and transplantation, a follow-up visit with psychiatry and social work will be arranged.
* DONOR: Unresolved sepsis.
* DONOR: Known history of urothelial or prostate cancer/malignancy.
* DONOR: Known history of bladder or prostate surgery.
* DONOR: Abnormal bladder capacity.
* DONOR: Active sexually transmitted disease.
* DONOR: Active cytomegalovirus (CMV), Epstein-Barr virus (EBV), or tuberculosis (TB) infections.
* DONOR: Hepatitis B virus (HBV) core antibody, surface antigen, or DANN positive.
* DONOR: Hepatitis C virus (HCV) antibody or viral load+.
* DONOR: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS).

Contacts and Locations

Study Contact

Ileana Aldana

CONTACT

323-865-0702

Ileana.aldana@med.usc.edu

Principal Investigator

Inderbir Gill

PRINCIPAL_INVESTIGATOR

University of Southern California

Study Locations (Sites)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033

United States

Collaborators and Investigators

Sponsor: University of Southern California

Inderbir Gill, PRINCIPAL_INVESTIGATOR, University of Southern California

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-01

Study Completion Date2026-05-01

Study Record Updates

Study Start Date2023-05-01

Study Completion Date2026-05-01

Terms related to this study

Keywords Provided by Researchers

neurogenic bladder
vascularized composite allograft

Additional Relevant MeSH Terms

Neurogenic Bladder
Bladder Dysfunction
Immunosuppression