CompletedNCT00579527#950Updated Mar 25, 2022Results posted

Phase I/II Thymus Transplantation With Immunosuppression #950

A Phase 1/2 interventional study of Cultured Thymus Tissue for Implantation (CTTI) and Cultured Thymus Tissue Implantation and Parental Parathyroid Transplantation in DiGeorge Anomaly, Complete DiGeorge Anomaly and Complete Atypical DiGeorge Anomaly, sponsored by Sumitomo Pharma Switzerland GmbH. Completed at 1 site in United States. Per ClinicalTrials.gov, last updated 2022-03-25.

Sponsored by Sumitomo Pharma Switzerland GmbH · Phase 1/2, Interventional, and Treatment

From the registry’s dates

Registered 2 years after the study started (first participant enrolled Dec 2005, registered Dec 2007).

Phase: Phase 1/2
Study type: Interventional
Enrollment: 14
Allocation: Non-randomized
Sex: All

Study summary

The study purpose is to determine if cultured thymus tissue implantation (CTTI) (previously described as transplantation) with tailored immunosuppression based on the recipient's pre-implantation T cell population is a safe and effective treatment for complete DiGeorge anomaly. This study will also evaluate whether cultured thymus tissue implantation and parathyroid transplantation with immunosuppression is a safe and effective treatment for complete DiGeorge anomaly and hypoparathyroidism.

Read the detailed description

Complete DiGeorge anomaly is a congenital disorder characterized by athymia. Without successful treatment, children remain immunodeficient and usually die by age 2 years. In infants with complete DiGeorge anomaly and no T cells, cultured thymus tissue implantation (CTTI) without immunosuppression resulted in diverse T cell development and good T cell function. Some infants with no thymus have some T cells that presumably developed extrathymically; these T cells can reject a thymus graft.

The purpose of this study is to tailor immunosuppression use for complete DiGeorge anomaly subjects who have some T cells and different T cell function levels. This protocol includes tailored immunosuppression regimens to allow subjects with different T cell function levels to be suppressed adequately.

Patients with complete DiGeorge often have hypoparathyroidism, a life threatening condition. Successful CTTI does not result in improvement of the hypoparathyroidism. The patients must go to the clinic for frequent calcium levels and to the hospital for calcium infusions. These infants are at risk for seizures from low calcium. This study had a parental parathyroid transplant arm for subjects with hypoparathyroidism who require calcium replacement.

Whether or not a subject was enrolled in the parathyroid arm, the immunosuppression regimen the subject received was dependent on the immune findings as stated in the clinical protocol.

Conditions studied

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

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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)

In context

DiGeorge Syndrome

47 studies on the registry are indexed under DiGeorge Syndrome; 10 are open to participants now.

This study's enrollment of 14 is below the median of 28 across 28 interventional studies indexed under DiGeorge Syndrome.

Browse DiGeorge Syndrome studies →

Lead sponsor

Sumitomo Pharma Switzerland GmbH is the lead sponsor of 15 studies on the registry; 3 are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 4 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Thymus Transplantation Inclusion:

Must have 1 of following: 22q11 or 10p13 hemizygosity; hypocalcemia requiring replacement; congenital heart defect; CHARGE association or CHD7 mutation; or abnormal ears plus mother w/diabetes (type I, type II, gestational).
\<50 CD3+ T cells/cumm or \<50 CD3+ T cells/cumm that are CD62L+ CD45RA+ (cluster of differentiation 45RA) (naïve phenotype), or \<5% of CD3+ count being CD62L+ CD45RA+

Atypical DiGeorge:

Must have, or have had, a rash. If rash present, rash biopsy must show T cells in skin. If rash \& adenopathy resolved, must have >50/cumm T cells \& naive T cell must be \<50/cumm or \<5% of T cells.

Typical DiGeorge:

CD3+ CD45RA+ CD62L+ T cells \<50/mm3 or \<5% of total T cells

Parathyroid Transplantation Additional Inclusion:

2 studies in recipient which PTH\<5 pg/ml when ionized calcium \<1.1 mmol/L. Can be done anytime pre-tx; 1 must be done while at Duke Hospital.
Parent(s) willing \& eligible to be donors

Thymus Transplantation Exclusion:

Heart surgery \<4 wks pre-tx
Heart surgery anticipated w/in 3 months after proposed tx
Rejection by surgeon or anesthesiologist as surgical candidate
Lack of sufficient muscle tissue to accept transplant of 4 grams/m2 BSA
HIV infection
Prior attempts at immune reconstitution, such as bone marrow tx or previous thymus tx
CMV(>500 copies/ml blood by PCR on 2 tests)
Ventilator dependence

Parathyroid Donor Inclusion:

>18 years of age
Serum calcium in normal range
Normal PTH function
HLA typing consistent with parentage
Not on anticoagulation or can come off
Parent chosen will share HLA-DR allele with thymus donor that was not inherited by the recipient. If no HLA matching at all, then either parent is acceptable if the parent meets other criteria.

Parathyroid Donor Exclusion:

\<18 years old
Hypoparathyroidism-low PTH in presence of low serum calcium \& high serum phosphate
Hyperparathyroidism(or history)-elevated PTH in presence of high serum calcium and low serum phosphate.
History of cancer
Donor only living involved parent/guardian of recipient
Evidence of HIV-1, HIV-2, HTLV-1, HTLV-2, syphilis, hepatitis B, hepatitis C, West Nile virus, or Chagas disease
Creutzfeldt Jakob disease (CJD)
Elevated liver function studies: AST, ALT, alkaline phosphatase >3x upper normal limit
Receipt of xenograft or risk factors for SARS, CJD and/or smallpox exposure. {If CJD risk factors but not active disease, parent may give permission for parathyroid use.}
Urine CMV positive
Positive CMV IgM
Positive IgM anti-EBV VCA
On blood thinners and cannot stop for parathyroid donation
Elevated PT or PTT (>ULN)
Platelets\<100,000
Positive Toxoplasma IgM
Donor will receive a history and physical; may be excluded based on PI's medical judgment.
Hemoglobin \<9g/dl
Infectious head or neck lesion
Goiter on ultrasound
Abnormal fiberoptic laryngoscopy of vocal cords
HLA inconsistent with parentage
Pregnancy
Positive HSV IgG isn't exclusion; post-tx prophylaxis needed for recipient if donor is HSV IgG+.
Positive VZV IgG isn't exclusion; post-tx prophylaxis needed if donor is VZV IgG+.
Medical concern of independent otolaryngologist.
Concern by medical psychologist/social worker that potential donor isn't competent or does not understand risks.
Questionnaire responses can lead to exclusion.

Mother of DiGeorge Inclusion:

Provides consent to use blood/buccal sample. No exclusions except unwillingness to consent; or, provide blood/buccal sample.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 14 participants (actual)

Study arms

Experimental
Cultured Thymus Tissue Implantation (CTTI) w/immunosuppression
Patients with complete DiGeorge Anomaly (cDGA) undergo cultured thymus tissue implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function.
Biological: Cultured Thymus Tissue for Implantation (CTTI) · Procedure: Blood Draw · Drug: Rabbit anti-thymocyte globulin · Drug: Cyclosporine · Drug: Tacrolimus · Drug: Methylprednisolone or Prednisolone · Drug: Daclizumab · Drug: Mycophenolate mofetil
Experimental
CTTI with Parathyroid Transplantation w/immunosuppression
Patients with complete DiGeorge Anomaly (cDGA) undergoes cultured thymus tissue thymus implantation (previously described as transplantation) with tailored immunosuppression based on the subject's pre-implantation T cell numbers and function. If the patient has hypoparathyroidism, and is eligible, the patient may also receive a parathyroid transplant.
Other: Cultured Thymus Tissue Implantation and Parental Parathyroid Transplantation · Procedure: Blood Draw · Drug: Rabbit anti-thymocyte globulin · Drug: Cyclosporine · Drug: Tacrolimus · Drug: Methylprednisolone or Prednisolone

Interventions

BiologicalCultured Thymus Tissue for Implantation (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.
Also known as: Thymus Tissue Transplant, CTTI
OtherCultured Thymus Tissue Implantation and Parental Parathyroid Transplantation
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.
Also known as: Thymus and Parathyroid Transplant, CTTI and Parathyroid Transplant
ProcedureBlood Draw
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.
Also known as: Venipuncture
DrugRabbit anti-thymocyte globulin
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.
Also known as: RATGAM, thymoglobulin
DrugCyclosporine
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.
Also known as: Csa
DrugTacrolimus
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.
Also known as: FK506
DrugMethylprednisolone or Prednisolone
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.
Also known as: Steroids
DrugDaclizumab
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.
Also known as: Zenapax
DrugMycophenolate mofetil
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.
Also known as: MMF, CellCept

What researchers measure

Primary outcomes

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.
Time frame: 1 year post-CTTI

Secondary outcomes

Survival at 2 Years Post-CTTI
Survival at 2 years 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.
Time frame: 2 years post-CTTI
Immune Reconstitution Efficacy - Total CD3 T Cells
The development of total CD3 T cells at one year as measured using flow cytometry
Time frame: 1 year post-CTTI
Immune Reconstitution Efficacy - Total CD4 T Cells
The development of total CD4 T cells at one year as measured using flow cytometry
Time frame: 1 year post-CTTI
Immune Reconstitution Efficacy - Total CD8 T Cells
The development of total CD8 T cells at one year as measured using flow cytometry
Time frame: 1 year post-CTTI
Immune Reconstitution Efficacy - Naive CD4 T Cells
The development of total naive CD4 T cells at one year as measured using flow cytometry
Time frame: 1 year post-CTTI
Immune Reconstitution Efficacy - Naive CD8 T Cells
The development of total naive CD8 T cells at one year as measured using flow cytometry
Time frame: 1 year post-CTTI
Immune Reconstitution Efficacy - Response to Mitogens
Measurement of the T cell proliferative response to the mitogen phytohemagglutin (PHA).
Time frame: 1 year post-CTTI
Thymus Allograft Biopsy
Evidence, on biopsy of the thymus tissue implanted in muscle, that shows the development of new T cells.
Time frame: 2 to 3 months post-CTTI

Results

Posted Feb 17, 2020

Participant flow

Participant flow — Overall Study
Milestone	Cultured Thymus Tissue Implantation w/ Immunosuppression
Started	14
Completed	10
Not completed	4
Withdrew: Death	4

Outcome measures

PrimarySurvival 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.

Time frame:: 1 year post-CTTI
Reported as:: Number · % of participants who survive to 1 year

Survival at 1 Year Post-CTTI
% of participants who survive to 1 year	Cultured Thymus Tissue With Immunosuppression
Survival at 1 Year Post-CTTI	71 (40.6 to 88.2)

SecondarySurvival at 2 Years Post-CTTI

Survival at 2 years 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.

Time frame:: 2 years post-CTTI
Reported as:: Number · % of participants who survive to 2 years

Survival at 2 Years Post-CTTI
% of participants who survive to 2 years	Cultured Thymus Tissue Implantation With Immunosuppression
Survival at 2 Years Post-CTTI	71 (40.6 to 88.2)

SecondaryImmune Reconstitution Efficacy - Total CD3 T Cells

The development of total CD3 T cells at one year as measured using flow cytometry

Time frame:: 1 year post-CTTI
Reported as:: Median · cells/mm3

Immune Reconstitution Efficacy - Total CD3 T Cells
cells/mm3	Cultured Thymus Tissue Implantation With Immunosuppression
Immune Reconstitution Efficacy - Total CD3 T Cells	726 (345 to 1866)

SecondaryImmune Reconstitution Efficacy - Total CD4 T Cells

The development of total CD4 T cells at one year as measured using flow cytometry

Time frame:: 1 year post-CTTI
Reported as:: Median · cells/mm3

Immune Reconstitution Efficacy - Total CD4 T Cells
cells/mm3	Cultured Thymus Tissue Implantation With Immunosuppression
Immune Reconstitution Efficacy - Total CD4 T Cells	593 (230 to 1780)

SecondaryImmune Reconstitution Efficacy - Total CD8 T Cells

The development of total CD8 T cells at one year as measured using flow cytometry

Time frame:: 1 year post-CTTI
Reported as:: Median · cells/mm3

Immune Reconstitution Efficacy - Total CD8 T Cells
cells/mm3	Cultured Thymus Tissue Implantation With Immunosuppression
Immune Reconstitution Efficacy - Total CD8 T Cells	145 (22 to 360)

SecondaryImmune Reconstitution Efficacy - Naive CD4 T Cells

The development of total naive CD4 T cells at one year as measured using flow cytometry

Time frame:: 1 year post-CTTI
Reported as:: Median · cells/mm3

Immune Reconstitution Efficacy - Naive CD4 T Cells
cells/mm3	Cultured Thymus Tissue Implantation With Immunosuppression
Immune Reconstitution Efficacy - Naive CD4 T Cells	156 (23 to 751)

SecondaryImmune Reconstitution Efficacy - Naive CD8 T Cells

The development of total naive CD8 T cells at one year as measured using flow cytometry

Time frame:: 1 year post-CTTI
Reported as:: Median · cells/mm3

Immune Reconstitution Efficacy - Naive CD8 T Cells
cells/mm3	Cultured Thymus Tissue Implantation With Immunosuppression
Immune Reconstitution Efficacy - Naive CD8 T Cells	37 (4 to 217)

SecondaryImmune Reconstitution Efficacy - Response to Mitogens

Measurement of the T cell proliferative response to the mitogen phytohemagglutin (PHA).

Time frame:: 1 year post-CTTI
Reported as:: Median · counts per minute (cpm)

Immune Reconstitution Efficacy - Response to Mitogens
counts per minute (cpm)	Cultured Thymus Tissue Implantation With Immunosuppression
Immune Reconstitution Efficacy - Response to Mitogens	139189 (13726 to 202132)

SecondaryThymus Allograft Biopsy

Evidence, on biopsy of the thymus tissue implanted in muscle, that shows the development of new T cells.

Time frame:: 2 to 3 months post-CTTI
Reported as:: Count of participants · Participants

Thymus Allograft Biopsy
Participants	Cultured Thymus Tissue Implantation With Immunosuppression
Evidence of thymopoiesis	7
Evidence of rejection	0
Inconclusive for thymopoiesis	3

Adverse events

Collected over 2 years post-CTTI. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cultured Thymus Tissue Implantation With Immunosuppression	4/14 (28.6%)	13/14 (92.9%)	14/14 (100%)

Most frequent serious events

Showing 10 of 42

Most frequent serious events
Event	Cultured Thymus Tissue Implantation With Immunosuppression
Device related infectionInfections and infestations	11/14
PyrexiaGeneral disorders	3/14
Cytokine release syndromeImmune system disorders	3/14
TachypnoeaRespiratory, thoracic and mediastinal disorders	2/14
NeutropeniaBlood and lymphatic system disorders	2/14
Cytomegalovirus infectionInfections and infestations	2/14
Respiratory failureRespiratory, thoracic and mediastinal disorders	1/14
Hypocalcaemic seizureNervous system disorders	1/14
Disseminated intravascular coagulationBlood and lymphatic system disorders	1/14
HaemolysisBlood and lymphatic system disorders	1/14

Most frequent other events

Showing 10 of 107

Most frequent other events
Event	Cultured Thymus Tissue Implantation With Immunosuppression
HypertensionVascular disorders	10/14
HypomagnesaemiaMetabolism and nutrition disorders	6/14
Cytokine release syndromeImmune system disorders	5/14
HypothyroidismEndocrine disorders	4/14
Urinary tract infection bacterialInfections and infestations	4/14
AnaemiaBlood and lymphatic system disorders	4/14
PyrexiaGeneral disorders	4/14
Alanine aminotransferase increasedInvestigations	4/14
TachypnoeaRespiratory, thoracic and mediastinal disorders	4/14
RashSkin and subcutaneous tissue disorders	4/14

Baseline characteristics

The study was designed to assess survival, without regard to the immune suppression used. No participants were enrolled into Arm 2. No subjects received a parathyroid transplant. Therefore, results are reported for Arm 1 only.

Age, Categorical
Age, Categorical(Participants)	Cultured Thymus Tissue Implantation With Immunosuppression
<=18 years	14
Between 18 and 65 years	0
>=65 years	0

Age, Continuous
Age, Continuous(days)	Cultured Thymus Tissue Implantation With Immunosuppression
Mean	248 ± 161

Sex: Female, Male
Sex: Female, Male(Participants)	Cultured Thymus Tissue Implantation With Immunosuppression
Female	5
Male	9

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Cultured Thymus Tissue Implantation With Immunosuppression
White	8
Black or African American	3
American Indian or Alaska Native	2
More than One Race (Caucasian/Asian)	1

Region of Enrollment
Region of Enrollment(Participants)	Cultured Thymus Tissue Implantation With Immunosuppression
United States	14

Study locations

1 site

Duke University Medical Center
Durham, North Carolina 27710, United States

References and documents

Publications

Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, Chinn IK, Hale LP, Kepler TB, He M, Sarzotti M, Skinner MA, Rice HE, Hoehner JC. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007 May 15;109(10):4539-47. doi: 10.1182/blood-2006-10-048652. Epub 2007 Feb 6. PubMed 17284531 ↗
Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, Sedlak DA, Sempowski GD, Hale LP, Rice HE, Mahaffey SM, Skinner MA. Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood. 2004 Oct 15;104(8):2574-81. doi: 10.1182/blood-2003-08-2984. Epub 2004 Apr 20. PubMed 15100156 ↗
Markert ML and Devlin BH. Thymic reconstitution (in Rich RR, Shearer WT, Fleischer T, Schroeder HW, Weyand CM, Frew A, eds., Clinical Immunology 3rd edn., Elsevier, Edinburgh) p 1253-1262, 2008.
Selim MA, Markert ML, Burchette JL, Herman CM, Turner JW. The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study. J Cutan Pathol. 2008 Apr;35(4):380-5. doi: 10.1111/j.1600-0560.2007.00816.x. PubMed 18333898 ↗
Chinn IK, Devlin BH, Li YJ, Markert ML. Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly. Clin Immunol. 2008 Mar;126(3):277-81. doi: 10.1016/j.clim.2007.11.009. Epub 2007 Dec 26. PubMed 18155964 ↗
Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, Sempowski GD, Rhein ME, Szabolcs P, Hale LP, Buckley RH, Coyne KE, Rice HE, Mahaffey SM, Skinner MA. Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases. J Allergy Clin Immunol. 2004 Apr;113(4):734-41. doi: 10.1016/j.jaci.2004.01.766. PubMed 15100681 ↗
Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP, Le Deist F, Alexieff MJ, Li J, Hauser ER, Haynes BF, Rice HE, Skinner MA, Mahaffey SM, Jaggers J, Stein LD, Mill MR. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood. 2003 Aug 1;102(3):1121-30. doi: 10.1182/blood-2002-08-2545. Epub 2003 Apr 17. PubMed 12702512 ↗
Li B, Li J, Devlin BH, Markert ML. Thymic microenvironment reconstitution after postnatal human thymus transplantation. Clin Immunol. 2011 Sep;140(3):244-59. doi: 10.1016/j.clim.2011.04.004. Epub 2011 Apr 16. PubMed 21565561 ↗
Chinn IK, Olson JA, Skinner MA, McCarthy EA, Gupton SE, Chen DF, Bonilla FA, Roberts RL, Kanariou MG, Devlin BH, Markert ML. Mechanisms of tolerance to parental parathyroid tissue when combined with human allogeneic thymus transplantation. J Allergy Clin Immunol. 2010 Oct;126(4):814-820.e8. doi: 10.1016/j.jaci.2010.07.016. Epub 2010 Sep 15. PubMed 20832849 ↗
Markert ML, Devlin BH, McCarthy EA. Thymus transplantation. Clin Immunol. 2010 May;135(2):236-46. doi: 10.1016/j.clim.2010.02.007. Epub 2010 Mar 16. PubMed 20236866 ↗
Markert ML, Li J, Devlin BH, Hoehner JC, Rice HE, Skinner MA, Li YJ, Hale LP. Use of allograft biopsies to assess thymopoiesis after thymus transplantation. J Immunol. 2008 May 1;180(9):6354-64. doi: 10.4049/jimmunol.180.9.6354. PubMed 18424759 ↗
Hudson LL, Louise Markert M, Devlin BH, Haynes BF, Sempowski GD. Human T cell reconstitution in DiGeorge syndrome and HIV-1 infection. Semin Immunol. 2007 Oct;19(5):297-309. doi: 10.1016/j.smim.2007.10.002. Epub 2007 Nov 26. PubMed 18035553 ↗
Markert ML, Devlin BH, Chinn IK, McCarthy EA, Li YJ. Factors affecting success of thymus transplantation for complete DiGeorge anomaly. Am J Transplant. 2008 Aug;8(8):1729-36. doi: 10.1111/j.1600-6143.2008.02301.x. Epub 2008 Jun 28. PubMed 18557726 ↗
Markert ML, Devlin BH, McCarthy EA, Chinn IK, Hale LP. Thymus Transplantation in Thymus Gland Pathology: Clinical, Diagnostic, and Therapeutic Features. Eds Lavinin C, Moran CA, Morandi U, Schoenhuber R. Springer-Verlag Italia, Milan, 2008, pp 255-267.
Markert ML, Devlin BH, Chinn IK, McCarthy EA. Thymus transplantation in complete DiGeorge anomaly. Immunol Res. 2009;44(1-3):61-70. doi: 10.1007/s12026-008-8082-5. PubMed 19066739 ↗
Chinn IK, Milner JD, Scheinberg P, Douek DC, Markert ML. Thymus transplantation restores the repertoires of forkhead box protein 3 (FoxP3)+ and FoxP3- T cells in complete DiGeorge anomaly. Clin Exp Immunol. 2013 Jul;173(1):140-9. doi: 10.1111/cei.12088. PubMed 23607606 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 25, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00579527
Lead sponsor: Sumitomo Pharma Switzerland GmbH
Collaborators: National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party: Sponsor
First posted: Dec 24, 2007
Start date: Dec 19, 2005
Primary completion: Dec 2011
Completion: Dec 31, 2017
Results posted: Feb 17, 2020
Last update: Mar 25, 2022

Study contacts

M. Louise Markert, MD, PhD

principal investigator · Duke University Medical Center, Pediatrics, Allergy & Immunology

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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