Using a new implant to help patients with esophageal reconstruction

Safety and Feasibility Study of the CELLSPAN Esophageal Implant (CEI) in Patients Requiring Short Segment Esophageal Replacement

This study is testing a new implant that uses a mix of synthetic material and the patient's own stem cells to help rebuild the esophagus in people who need reconstruction.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Harvard Apparatus Regenerative Technology, Inc. (industry)
• Drugs / interventions: CAR-T, chimeric antigen receptor, chemotherapy, prednisone
• Locations: 3 sites (Los Angeles, California and 2 other locations)
• Trial ID: NCT05877300 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and feasibility of the Cellspan Esophageal Implant (CEI), which combines a synthetic scaffold with the patient's own stem cells to regenerate a living esophageal conduit. It is a first-in-human, single-arm, multicenter trial involving up to 10 subjects across 5 centers in the United States. Participants will be monitored for at least 2 years following the implantation to assess the effectiveness and safety of the procedure. An independent Data Monitoring Committee will oversee the safety of the subjects throughout the study.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with severe esophageal conditions who have failed multiple previous treatments.

Not a fit: Patients with esophageal conditions that do not require reconstruction or those who have not failed prior treatment modalities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients requiring esophageal reconstruction, potentially improving their quality of life.

How similar studies have performed: While this approach is novel, similar regenerative medicine techniques have shown promise in other organ systems, indicating potential for success.

Eligibility criteria

Inclusion Criteria Cohort 1:

1. Subject ≥18 years of age
2. The patient has medical conditions requiring esophageal reconstruction, such as, but not limited to:

   1. Refractory benign esophageal strictures (RBES)
   2. Esophageal perforation (full thickness)
   3. Chronic/persistent esophageal fistula
   4. Combination of esophageal perforations/fistula with RBES
3. The patient must have failed at least 3 previous treatment modalities to correct the medical esophageal condition (a-d).

   a. If RBES: i. Steroid treatment ii. Esophageal balloon dilation (EBD) iii. Stent use ≥ 6 months iv. Endoscopic incisional repair

   b. If esophageal perforation: i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent use ≥ 6 months iv. Primary surgical repair

   c. If Chronic/Persistent fistula(e): i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent ≥ 6 months iv. Primary surgical repair

   d. If Combination Perforation/fistula with RBES i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent use ≥ 6 months iv. Primary surgical repair
4. The patient must be a surgical candidate for a short segment esophageal reconstruction (≤6 cm full circumferential segmental excision)
5. The location of the esophageal segment for surgical resection is within the thoracic cavity, defined as, above the diaphragm and at least 4 cm below the larynx.
6. The patient must be a high-risk candidate for minimally invasive esophageal reconstruction, based upon the investigator's determination. The patient requires a thoracotomy to repair the esophagus and is not amenable for laparoscopic or robotic minimally invasive gastric pull-up (GPU) surgery, due to a medical contraindication
7. All patients must be made aware and must be amenable to a delayed rescue repair surgical procedure in the event the CEI fails to restore a patent durable biologic esophageal conduit
8. The patient/guardian is willing and able to comply with the protocol specified medication regimen and follow-up evaluations
9. The patient/guardian has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)

Inclusion Criteria Cohort 2:

1. Subject ≥18 years of age
2. The patient has medical conditions requiring esophageal reconstruction, limited to:

   a. Spit Fistula with an upper esophageal ostomy in the neck
3. Patients may require esophageal de-functioning with a resulting cervical spit fistula if they are not candidates for immediate esophageal reconstruction. This may occur for multiple reasons, including being too sick for reconstruction, healing of the airway after tracheo-esophageal fistula repair, requirement for further therapy prior to reconstruction, or recovering from sepsis due to esophageal perforation.
4. The patient must be a surgical candidate for a short segment esophageal reconstruction (\< 7cm), a full circumferential segmental esophageal extension in order to have sufficient length to make the anastomosis to the distal thoracic esophagus, to a gastric or to an intestinal interposition conduit that will re-establish oral nutritional intake. i.
5. Patient must be a high-risk candidate for the standard of care treatment of esophageal reconstruction, based upon the investigator's determination. The patient requires a thoracotomy to repair the esophagus following the CEI subdermal extension procedure and is not amenable for laparoscopic or robotic minimally invasive gastric pull-up (GPU) surgery.
6. All patients must be made aware and must be amenable to a delayed rescue repair surgical procedure in the event the CEI fails to mature in the subdermal area prior to mobilization
7. The patient/guardian is willing and able to comply with the protocol- specified medication regimen and follow-up evaluations
8. The patient/guardian has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC).

Exclusion Criteria all cohorts:

1. Subject requires or undergoes an esophageal segmental excision \>6 cm in length
2. Esophageal segment extends below the diaphragm or \<4 cm below larynx
3. Pre-existing implants/structures adjacent to target surgical location for implant that could cause abrasion of the scaffold/regenerated tissue (e.g., pacemaker lead, vascular clips, vascular grafts).
4. Known clinical contraindication that would obfuscate the use of the covered metallic stent to be used as an adjunct to the procedure
5. Post ablation stricture for Barrett's esophagus treated less than 1 year prior to planned procedure
6. Patient has a comorbidity or contraindication that would preclude any study required procedures including adipose tissue biopsy and esophageal resection surgery. Comorbidities are defined from a subset of the Charlson Comorbidities Index (CCI, Yamashita 2018) scoring system and include:

   1. diabetes mellitus (CCI = 1)
   2. connective tissue disorders (CCI=1)
   3. immune compromised
   4. chemotherapy radiotherapy or chemoradiotherapy (within 60 day clearance)
   5. inability to tolerate major thoracotomy
   6. active infection at the biopsy or thoracotomy incision site
   7. peripheral vascular disease (CCI=1)
   8. all patients with a CCI\> 2
7. Life expectancy of less than 1 year
8. Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following the index procedure. Female patients of childbearing potential must have a negative pregnancy test (per site standard test) within 7days prior to index procedure.
9. Has a known untreated neurological, psychological, psychiatric, or other disorder that would interfere with trial endpoints or with cooperation with the requirements of the trial
10. Has a diagnosis of immunodeficiency, receiving cancer therapy including chimeric antigen receptor T cells (CAR-T), receiving systemic steroid therapy (\>10 mg prednisone or equivalent daily dose), or any other form of pharmacologic therapy that would inhibit the intended cell growth (e.g., protease inhibitors, immunosuppressants, anti-cytokine therapies) within 30 days prior to index procedure or intended for use during any time after implantation through 12 months post-index procedure.
11. Patient with an infection requiring antibiotic therapy
12. Known allergy to Nitinol (for adjunctive self-expanding covered metallic stent procedure)
13. Current participation in another investigational drug or device study
14. Patient is a prisoner
15. If in the opinion of the investigator, the patient requires pain management (potentially opioid medications) as a result of study participation, the patient is at an unreasonable risk of addiction. This decision may be based upon medical or social history, personal situation, or the expected time course, length, and type of medication use.

Where this trial is running

Los Angeles, California and 2 other locations

• Keck Medical Center of University of Southern California — Los Angeles, California, United States (RECRUITING)
• University of Michigan — Ann Arbor, Michigan, United States (RECRUITING)
• Mayo Clinic — Rochester, Minnesota, United States (RECRUITING)

Study contacts

• Study coordinator: Shunfu Hu, Phd.

Conditions: Esophageal Diseases, Esophagus, Esophagectomy, Tissue Engineering, Organ Regeneration, Regenerative Medicine, Cell Therapy, Dual Arm