Clinical trial NCT00597441: Phase I Study of Umbilical Cord Blood Transplantation Followed by Third Party Thymus Transplantation
Official title: Phase I Study of Umbilical Cord Blood Transplantation Followed by Third Party Thymus Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Stem Cell Transplantation
Keywords: unrelated
umbilical cord blood transplantation
thymus transplantation
Lead sponsor: Sumitomo Pharma Switzerland GmbH
Sponsor class: INDUSTRY
First posted: 2008-01-18
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 5 years
Secondary outcomes:
measure: 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.
timeFrame: 5 years
measure: 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.
timeFrame: 5 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: Mitchell Horwitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke Health
name: Mary L Markert, MD
role: PRINCIPAL_INVESTIGATOR
References: