Phase I/II Thymus Transplantation With Immunosuppression #950

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages Any age
• All sexes
• No healthy volunteers
• Child, Adult, Older adult

Trial locations and contacts

1 site in 1 country.

About this study

Official title: Phase I/II Trial of Thymus Transplantation With Immunosuppression, #950

Conditions

DiGeorge Anomaly, Complete DiGeorge Anomaly, Complete Atypical DiGeorge Anomaly, Complete DiGeorge Syndrome, Complete Atypical DiGeorge Syndrome

Being tested

Cultured Thymus Tissue for Implantation (CTTI), Cultured Thymus Tissue Implantation and Parental Parathyroid Transplantation, Blood Draw, Rabbit anti-thymocyte globulin, Cyclosporine

Keywords

DiGeorge Anomaly, Thymus Transplantation, DiGeorge Syndrome, Athymia, Parathyroid Transplantation, Hypocalcemia, Hypoparathyroidism, Low T cell numbers, Immunoreconstitution, Immunodeficiency, Complete DiGeorge Anomaly, Complete Atypical DiGeorge Anomaly, Complete DiGeorge Syndrome, Complete Atypical DiGeorge Syndrome, Cultured Thymus Tissue Implantation (CTTI)

Medical subject headings

DiGeorge Syndrome, Thymic aplasia, Hypocalcemia, Hypoparathyroidism, Immunologic Deficiency Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• Cultured Thymus Tissue for Implantation (CTTI)Biological

  Also called Thymus Tissue Transplant, CTTI

  Potential thymus recipient subjects are screened for eligibility. Thymus donor (unrelated donor), and thymus donor's birth mother are screened for safety. CTTI is done under general anesthesia in the operating room. Cultured thymus tissue is implanted into the subject's quadriceps. Two to three months post CTTI, if medically stable, the subject undergoes allograft biopsy. At the time of implantation and biopsy, a skin biopsy is done. Immunosuppression is weaned as per protocol.

• Cultured Thymus Tissue Implantation and Parental Parathyroid TransplantationOther

  Also called Thymus and Parathyroid Transplant, CTTI and Parathyroid Transplant

  For subjects w/ hypoparathyroidism, the subject may receive CTTI and parathyroid transplant. For parathyroid transplant, parental parathyroid donors are screened. Parathyroid is harvested from the parent who shares the most Human Leukocyte Antigens (HLA) alleles with the thymus donor. Parathyroid gland is minced and placed in quadriceps muscle; there is no dose. Parathyroid donors are monitored as outpatients until recipients' discharge. Recipients' calcium and PTH levels are monitored indefinitely. Potential thymus recipient subjects are screened for eligibility. Thymus donor (unrelated donor), and thymus donor's birth mother are screened for safety. CTTI is done under general anesthesia in the operating room. Cultured thymus tissue is implanted into the subject's quadriceps. Two to three months post CTTI, if medically stable, the subject undergoes allograft biopsy. At the time of CTTI and biopsy, a skin biopsy is done. Immunosuppression is weaned as per protocol.

• Blood DrawProcedure or surgery

  Also called Venipuncture

  Birth mothers of Thymus Recipients are asked to participate in the study and undergo phlebotomy to allow testing of T cell identity in the Complete DiGeorge subjects. If blood is not obtainable then a buccal swab may be done.

• Rabbit anti-thymocyte globulinDrug

  Also called RATGAM, thymoglobulin

  Three doses of 2 mg/kg IV (through a central venous catheter) prior to CTTI. Each dose of Rabbit anti-thymocyte globulin (RATGAM) is given over 12 hours. RATGAM is usually given on days-5, -4, and -3 prior to CTTI or CTTI and parathyroid transplantation. Medications (diphenhydramine, steroids, and acetaminophen) are given with rabbit anti-thymocyte globulin.

• CyclosporineDrug

  Also called Csa

  In addition to RATGAM, subjects with typical cDGA with PHA responses >50,000 cpm, or atypical cDGA with PHA response <75,000cpm (when not on immunosuppression) or <40,000 cpm to PHA while on immunosuppression, are started on cyclosporine (Csa) as soon as cDGA is diagnosed. Csa is continued with target trough levels of 180 to 220 ng/ml. If subject cannot tolerate Csa, Csa may be changed to tacrolimus (FK506) with target trough level 7 to 10 ng/ml. When trough levels are outside of range, dosing is modified appropriately.

  Csa may be given every 8 to 12 hours enterally or IV before and after CTTI. The Csa dose is dependent on T cell numbers and the target Csa trough levels. Csa is weaned as per protocol.

• TacrolimusDrug

  Also called FK506

  If unable to tolerate cyclosporine, then tacrolimus is given. Tacrolimus may be given every 8 to 12 hours enterally or IV before and after the CTTI transplant. Tacrolimus dose is dependent on the T cell numbers and the target tacrolimus trough levels. Tacrolimus is weaned as per protocol.

• Methylprednisolone or PrednisoloneDrug

  Also called Steroids

  Steroids IV or enterally may be given before and after CTTI or CTTI and parathyroid transplantation. Administration and dosage depends on T cell numbers and symptoms. Pre-transplant steroids may be used when pre-transplant T cells >4,000cumm. Steroids are weaned as per protocol.

• DaclizumabDrug

  Also called Zenapax

  In addition, subjects with Atypical DiGeorge with PHA responses >75,000cpm while on no immunosuppression or PHA responses >40,000cpm while on immunosuppression, Daclizumab 1 mg/kg single dose IV may be given depending on T cell counts. Administration of Daclizumab depends on T cell numbers and T cell activation. A single dose may be given after the administration of rabbit anti-thymocyte globulin and before CTTI. If Daclizumab is not given before CTTI, and, depending on the T cell numbers and T cell activation, a single dose of Daclizumab may be given 3-5 days after CTTI.

• Mycophenolate mofetilDrug

  Also called MMF, CellCept

  In addition, subjects with Atypical DiGeorge with PHA responses >75,000cpm while on no immunosuppression or PHA responses >40,000cpm while on immunosuppression, Mycophenolate mofetil 15 mg/kg/dose every 8 hours IV or enterally may be given depending on T cell counts. Mycophenolate mofetil may be given if the T cell count remains elevated 5 days after CTTI. If MMF is given, the dose is 15 mg/kg IV. MMF may be stopped at 35 days after CTTI or continued for up to six months after CTTI.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Survival at 1 Year Post-CTTI

   Survival at 1 year post cultured thymus tissue implantation was assessed using the Kaplan Meier Estimated Survival. This mathematical function estimates the survival for a certain length of time.

   Measured: 1 year post-CTTI

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted24 Dec 2007 (estimated)
2. Study start19 Dec 2005
3. Primary completionDec 2011
4. Study completion31 Dec 2017

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Publications (16)Papers the sponsor has linked to this study.
• Other trials for DiGeorge AnomalyStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.