Phase I Study of Umbilical Cord Blood Transplantation Followed by Third Party Thymus Transplantation

The objective of this trial is to assess the toxicity of thymus transplantation following unrelated umbilical cord blood transplantation. Emphasis will be placed on adverse events that are not typically associated with umbilical cord blood transplantation. Also, to determine whether engraftment of a third party thymus allograft is feasible in patients who have undergone unrelated umbilical cord blood transplantation.

Study Overview

• Status: Terminated
• Conditions: Stem Cell Transplantation
• Intervention / Treatment: Biological: Thymic Transplantation for Recipients of UCB transplant

Detailed Description

The objective of this trial is to assess the toxicity of thymus transplantation following unrelated umbilical cord blood transplantation. Emphasis will be placed on adverse events that are not typically associated with umbilical cord blood transplantation. Also, to determine whether engraftment of a third party thymus allograft is feasible in patients who have undergone unrelated umbilical cord blood transplantation. Thymic engraftment will be determined by biopsy of the thymus allograft and immunohistochemical evidence of thymopoiesis. In addition, we would like to assess thymic function by measuring the number of naive T cells and the number of T cell receptor rearrangement excision circles (TRECS), and by assessing the diversity of the T cell receptor beta chain. These data will be compared to age, stem-cell donor source and disease matched historical controls whose stem cell transplants were not followed by a thymus transplant. This will be done in descriptive fashion. Other immune parameters will be followed including T, B, and NK cell numbers, T cell responses to mitogens, antigens, and immunoglobulin production.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who received a dual cord blood transplant are eligible and must have achieved donor cord blood chimerism of > 75% in both T-cell and myeloid lineages
• At the time of thymus transplantation, subjects cannot have active grade II-IV acute graft versus host disease.
• At the time of thymus transplantation, the subject must have an absolute neutrophil count of > 500/ul and a platelet count of 50,000/ul (even if achieved via transfusion).
• At the time of thymus transplantation, the subject must have < or equal to 50 circulating CD 34+ cells/ul (as measured within 3 weeks of transplant date).
• At the time of thymus transplantation, subjects cannot be on greater than 2 mg/kg/day methylprednisolone or its equivalent of steroids.
• At the time of thymus transplantation, PT and PTT must be less that 1.5 times the ULN or must be correctable to this level.
• At the time of thymus transplantation, subjects cannot require oxygen or have pulmonary disease that would be thought to make general anesthesia a high risk.
• Subjects must be between the ages of 18 and 60 years of age.

Exclusion Criteria:

• Subjects cannot have bone marrow flow cytometry demonstrating residual leukemia
• Subjects cannot have insufficient subcutaneous tissue and muscle mass to be able to accept and heal a thymus transplant, as assessed by a surgeon.
• Prior to thymus transplantation, subjects cannot have evidence of active disease with HHV6, West Nile Virus, EBV, and CMV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I; Thymic tissue from third party donor	Biological: Thymic Transplantation for Recipients of UCB transplant; Subjects with hematologic malignancies or bone marrow failure disorders will undergo umbilical cord blood transplantation and two months post transplant will have thymic tissue from a third party donor transplanted into the thigh muscle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity of thymus transplantation following unrelated umbilical cord blood transplantation. Emphasis will be placed on adverse events that are not typically associated with umbilical cord blood transplantation.	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine whether engraftment of a third party thymus allograft is feasible in patients who have undergone unrelated UCBT. Thymic engraftment will be determined by biopsy of the thymus allograft and immunohistochemical evidence of thymopoiesis.	5 years
To assess thymic function by measuring the number of naive T cells and the number of T cell receptor rearrangement excision circles (TRECS), and by assessing the diversity of the T cell receptor beta chain.	5 years

Collaborators and Investigators

• Sponsor: Enzyvant Therapeutics GmBH
• Investigators: Principal Investigator: Mary L Markert, MD, Duke Health

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: December 27, 2007
• First Submitted That Met QC Criteria: January 10, 2008
• First Posted (Estimate): January 18, 2008

Study Record Updates

• Last Update Posted (Actual): April 1, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: unrelated; umbilical cord blood transplantation; thymus transplantation
• Other Study ID Numbers: Pro00007995