Human Penile Tissue Allotransplantation for Devastating Penile and Concomitant Genital Trauma

Phase 1

Withdrawn

• Conditions: Urologic Injuries; Genital Diseases, Male; Amputation
• Interventions: Procedure: Penile Transplant; Biological: Monoclonal Antibody (Humanized Anti-CD52); Drug: Tacrolimus

• Registration Number: NCT03240822
• Lead Sponsor: Wake Forest University Health Sciences

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.

Study Timeline

• Study Start: 2017-01
• Study First Submitted: 2017-08-02
• Study First Submitted QC: 2017-08-04
• Study First Posted: 2017-08-07
• Status Verified: 2020-07
• Last Update Submitted: 2021-04-09
• Last Update Posted: 2021-04-14
• Primary Completion: 2022-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

For Recipients

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

For Recipients

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Penile Allotransplant and Immunosuppression Treatment	Penile Transplant	Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.
Penile Allotransplant and Immunosuppression Treatment	Monoclonal Antibody (Humanized Anti-CD52)	Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.
Penile Allotransplant and Immunosuppression Treatment	Tacrolimus	Penile transplantation with monoclonal antibody induction therapy of humanized anti CD52 followed by donor bone marrow infusion and tacrolimus monotherapy.

Primary Outcome Measures

Name	Time	Method
Need for Immunosuppressive drug therapy	6 months	The amount of immunosuppressive drug therapy will be recorded.

Secondary Outcome Measures

Name	Time	Method
erectile function	6 months	This will be assessed following intracorporal injection of vaso-active agents, such as prostaglandin, phentolamine, papaverine, or some mixture of these drugs (i.e. Trimix). and through high-resolution duplex Doppler ultrasonography
Assessment of sensory return and sensory thresholds	6 months	This will be accomplished by penile biothesiometry
Determination of hemodynamic status	6 months	Dynamic infusion pharmaco-cavernosometry and cavernosography will be utilized to better understand these changes
The Reintegration to Normal Living (RNL) Index	6 months	The RNL is an 11-item questionnaire that asks how a person manages activities, roles, and relationships on a day-to-day basis.
The Situational Inventory of Body-Image Dysphoria (SIBID)	6 months	The SIBID is a multidimensional body-image survey assessment of people's negative body-image emotions in everyday situations and physical experiences.
The Function and Body Image Survey	6 months	This survey consists of six open-ended questions regarding personal thoughts, opinions, and experiences about the transplant, and the individual's current functional abilities.