Athymia, Immunodeficiency, Immunoreconstitution, Low T Cell Numbers, Poor Thymic Function, Thymus Transplantation
Conditions
Keywords
Cultured Thymus Tissue Implantation
Brief summary
The primary purpose is to provide access for patients who have immunodeficiency or severe autoimmune disease related to poor thymic function to cultured thymus tissue for implantation. With no thymus function, bone marrow stem cells do not develop into educated T cells, which fight infection. Eligible participants receive cultured thymus tissue for implantation and may undergo biopsy. Immune suppression may be given depending on the immune status and clinical condition of the participant. Immune function testing is continued for one year post-implantation.
Detailed description
The patients enrolled have a high likelihood of death if they do not receive culture thymus tissue because of lack of thymus function. As there are many types of patients who may be enrolled, study results will not have statistical significance. The study objective is to make cultured thymus tissue available for implantation on an expanded access basis. Data will be collected on survival, naïve T cell development, T cell chimerism, and implant related toxicities, as well as any unexpected study-related serious adverse events. Eligible subjects receive cultured thymus tissue and may undergo allograft biopsy. Immune suppression may be given depending on the subject's immune status and clinical condition. Protocol specified studies continue until approximately one year post-implantation. Study participation lasts approximately two years.
Interventions
BIOLOGICALCultured Thymus Tissue
Subjects receive cultured thymus tissue which is implanted into the quadriceps muscle. Subjects may receive pre and/or post-implantation immunosuppression. Potential subjects are screened for eligibility. The thymus tissue (from an unrelated donor), the donor, and the donor's mother are screened for safety. Cultured thymus tissue is implanted into the subject's quadriceps muscle under general anesthesia in the operating room. Two to three months post-implantation, if medically stable, subjects may undergo an allograft biopsy. Subjects undergo laboratory testing for approximately one year post-implantation. At year 2 post-implantation, subjects are contacted for data collection.
PROCEDUREBlood Draw
DRUGRabbit Anti-Thymocyte Globulin and Cyclosporine or Tacrolimus
RATGAM and Cyclosporine or Tacrolimus may be given, depending on the patient. The doses, timing, and trough levels will vary depending on the patient's clinical condition.
Sponsors
Sumitomo Pharma Switzerland GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Cultured Thymus Tissue Inclusion Criteria for Implantation: * an immunodeficiency or severe autoimmunity for which development of naïve T cells would be expected to lead to lead to clinical improvement. * written consent (or consent of parent/legal guardian as applicable), review of medical testing, laboratory studies, and physical examinations are used to determine whether the patient is clinically stable and will potentially benefit from receiving cultured thymus tissue. Each participant is reviewed with the Data Safety and Monitoring Board (DSMB). Cultured Thymus Tissue
Exclusion criteria
for Implantation: * Unrepaired cyanotic congenital heart disease * Uncontrolled infections. Uncontrolled is defined as requiring a ventilator, dialysis, or vasopressor support or anticipated as requiring such support within 6 months. * Pregnancy * For females of child-bearing potential, a serum pregnancy test is done after consent, at the same time another blood draw is done if possible. * Females of child-bearing potential must agree to contraceptive measures as indicated in the consent form. * A second serum pregnancy test is done within 48 hours prior to administration of study interventions involving FDA pregnancy class D drugs, chemotherapy drugs, or other drugs or interventions known to pose risks to a potential fetus. * HIV Positive * History of malignancy * CMV Infection * For subjects receiving immunosuppression as part of the implantation protocol, CMV infection as documented by \>500 copies/ml in blood by PCR on two consecutive assays is an exclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Survival Rate at End of 1 Year | 1 Year |
| Survival Rate at End of 2 Year | 2 Year |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cultured Thymus Tissue Implantation Cultured thymus tissue for the treatment of immunodeficiency and autoimmune disorders | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 3 |
Baseline characteristics
| Characteristic | Cultured Thymus Tissue Implantation |
|---|---|
| Age, Continuous | 1485.5 days STANDARD_DEVIATION 1601.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 8 / 11 |
Outcome results
Primary
Survival Rate at End of 1 Year
Time frame: 1 Year
Population: Efficacy Analysis Set (EAS): EAS set includes all subjects with athymia associated with complete DiGeorge anomaly or FoxN1 deficiency, who had no prior hematopoietic cell transplant (HCT) and were treated with cultured postnatal thymus tissue in study 51692
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cultured Thymus Tissue Implantation | Survival Rate at End of 1 Year | 90.9 percentage of participants |
Primary
Survival Rate at End of 2 Year
Time frame: 2 Year
Population: Efficacy Analysis Set (EAS): EAS set includes all subjects with athymia associated with complete DiGeorge anomaly or FoxN1 deficiency, who had no prior hematopoietic cell transplant (HCT) and were treated with cultured postnatal thymus tissue in study 51692
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cultured Thymus Tissue Implantation | Survival Rate at End of 2 Year | 87.5 percentage of participants |