Human Penile Tissue Allotransplantation for Devastating Penile and Concomitant Genital Trauma

NCT ID: NCT03240822

Last Updated: 2021-04-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2025-12-31

Brief Summary

This is a 4-year, non-randomized, single center, patient self-controlled, clinical trial (though enrolled subjects will be followed for life as are all transplant patients) for patients seeking allotransplantation of the male external genitalia (MEG), or penile tissue, as a feasible reconstructive strategy for the treatment of devastating and irreversible injuries to the genitalia. In addition to receiving penile allotransplantation and post-operative monitoring and support, enrolled patients will receive an innovative and clinically proven immunomodulatory protocol that combines lymphocyte depletion of the recipient with donor bone marrow cell infusion. Patients will be treated with lymphocyte depleting induction therapy, donor bone marrow cell infusion and tacrolimus. After the first year, maintenance immunosuppression will be modified gradually and cautiously (tapered dose reduction or spaced frequency dosing of tacrolimus) in selected patients based on a critical evaluation of clinical and immunologic outcomes. Outcomes will include but not be limited to functional metrics (sensation, erection, voiding), psychosocial (body integrity, adaptation to transplant) and health related quality of life (HRQOL) measures.

Detailed Description

Initial treatment with an antibody targeting recipient immune cells followed by triple-drug maintenance therapy represents the current standard in clinical VCA. Our protocol is different from the existing conventional drug treatments used in MEG allotransplantation in that it combines donor bone marrow infusion with an immunosuppression sparing protocol. The primary goal of this pilot clinical trial is to determine the feasibility of using allogeneic penile tissue to repair/replace irreversibly damaged external genitalia. Enrolled and transplanted subjects will be followed for their lifetime as a transplant patient.

Conditions

Urologic Injuries; Genital Diseases, Male; Amputation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Penile Allotransplant and Immunosuppression Treatment

Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.

Group Type: EXPERIMENTAL

Penile Transplant

Intervention Type: PROCEDURE

Penile Allotransplantation

Monoclonal Antibody (Humanized Anti-CD52)

Intervention Type: BIOLOGICAL

Tacrolimus

Intervention Type: DRUG

Interventions

Penile Transplant

Penile Allotransplantation

Intervention Type: PROCEDURE

Monoclonal Antibody (Humanized Anti-CD52)

Intervention Type: BIOLOGICAL

Tacrolimus

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male

2. 18-40 years

3. Irreversible and devastating genitalia damage not amenable to conventional reconstruction.

4. Patent main vessels leading into the remaining penile stump, as confirmed by angiography.

5. Adequate penile stump (> 2.5cm) to facilitate placement of a tourniquet, debridement of the distal portion and sufficient distal mobilization of the structures requiring anastomosis

6. Eligible for long term standard of care coverage

Exclusion Criteria

1. Documented history of:

1. cancer

2. renal impairment

3. hepatic disorders

4. neurologic disorders (sensory or motor function deficits)

5. severe scarring with poor host tissue bed

6. penile resection or implant surgery

7. diabetes

8. hypertension

9. hyperlipidemia

10. coronary artery disease

11. untreated genital cancer

12. HIV, Hepatitis B or C, or any infectious disease

13. erectile dysfunction

14. Peyronie's disease

15. urethral stricture disease

16. balanitis

17. xerotica obliterans

18. pelvic embolization

19. pelvic radiation

20. untreated hypogonadism

21. prior prostate surgery

22. recurrent urinary tract infections (UTIs)

23. nephrolithiasis

24. connective tissue disease or collagen disease

25. lipopolysaccharidosis or amyloidosis

2. Use of 5-alpha-reductase inhibitors

3. External signs, sequelae or positive serology of sexually transmitted disease (including HPV)

4. Active UTI, stones, urethral edema and other pathology that prevents urethral anastomosis

5. Current or past substance abuse

6. Current or past smoker (within past 3 months)

7. Use of any medications known to cause vasoconstriction

8. Psychiatric illness or psychological problems, or deemed unsuitable on psychiatric evaluation

9. Any condition that may prevent transplantation (positive cross match, high panel reactive antibody (PRA), etc.)

10. Uncontrolled bleeding disorder, platelet count > 50,000, hemophilia or any other inherited coagulopathy or need to routinely receive blood products for bleeding disorders

11. Concurrent participation in any other clinical investigation during the period of this investigation

12. Inability to undergo leukapheresis

13. Inability to participate in all necessary study activities due to physical or mental limitations

14. Inability or unwillingness to return for all required follow-up visits.

15. Inability or unwillingness to sign the patient informed consent document.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony Atala, MD

Role: PRINCIPAL_INVESTIGATOR

Professor

Other Identifiers

IRB00027539

Identifier Type: -

Identifier Source: org_study_id