Poor Thymic FunctionPhase 4NCT02274662

Expanded Access Protocol Thymus Transplantation

A Phase 4 study testing Cultured Thymus Tissue, Blood Draw and Rabbit Anti-Thymocyte Globulin and Cyclosporine or Tacrolimus in people with Poor Thymic Function and Immunodeficiency, run by Sumitomo Pharma Switzerland GmbH.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Any age
Conditions the study is for: Poor Thymic Function, Immunodeficiency, Athymia
What is being tested?: Cultured Thymus Tissue, Blood Draw and Rabbit Anti-Thymocyte Globulin and Cyclosporine or Tacrolimus
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: No sites listed yet
Study dates: Aug 2014to Aug 2023
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

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.

About this study

Official title: Expanded Access Protocol Thymus Transplantation for Immunodeficiency, Hematologic Malignancies, and Autoimmune Disease Related to Poor Thymic Function

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.

Read the 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.

Conditions: Poor Thymic Function, Immunodeficiency, Athymia, Immunoreconstitution, Thymus Transplantation, Low T Cell Numbers
Being tested: Cultured Thymus Tissue, Blood Draw, Rabbit Anti-Thymocyte Globulin and Cyclosporine or Tacrolimus
Keywords: Cultured Thymus Tissue Implantation
Medical subject headings: Immunologic Deficiency Syndromes, Thymic aplasia

What participants receive

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

Cultured Thymus TissueBiological
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.
Blood DrawProcedure or surgery
Also called Venipuncture
Rabbit Anti-Thymocyte Globulin and Cyclosporine or TacrolimusDrug
Also called RATGAM and Csa or FK506
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.

Study groups in NCT02274662
Study group	Role	What they receive
Cultured thymus tissue implantation (CTTI)	Experimental	Cultured thymus tissue for the treatment of immunodeficiency and autoimmune disorders Receives: Biological: Cultured Thymus Tissue; Procedure: Blood Draw; Drug: Rabbit Anti-Thymocyte Globulin and Cyclosporine or Tacrolimus

What is being measured

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

Survival Rate at End of 1 Year
Measured: 1 Year
Survival Rate at End of 2 Year
Measured: 2 Year

Timeline

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

Aug 2014Aug 2023

First posted24 Oct 2014 (estimated)
Study startAug 2014
Primary completionAug 2023
Study completionAug 2023

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 (24)Papers the sponsor has linked to this study.
Other trials for Poor Thymic FunctionStudies 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.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02274662
Sponsor's protocol ID: Pro00051692
Status last verified: Dec 2024
First submitted: 22 Oct 2014
Last updated: 16 Jan 2025
Results posted: Yes, on ClinicalTrials.gov

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, 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, 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
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, 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. Thymus transplantation in complete DiGeorge anomaly. Immunol Res. 2009;44(1-3):61-70. doi: 10.1007/s12026-008-8082-5.
PubMed 19066739
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, 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 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.
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
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, Marques JG, Neven B, Devlin BH, McCarthy EA, Chinn IK, Albuquerque AS, Silva SL, Pignata C, de Saint Basile G, Victorino RM, Picard C, Debre M, Mahlaoui N, Fischer A, Sousa AE. First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood. 2011 Jan 13;117(2):688-96. doi: 10.1182/blood-2010-06-292490. Epub 2010 Oct 26.
PubMed 20978268
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

Study at a glance

From the registry record, last updated by the sponsor on 16 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Expanded Access Protocol Thymus Transplantation for Immunodeficiency, Hematologic Malignancies, and Autoimmune Disease Related to Poor Thymic Function
ClinicalTrials.gov ID: NCT02274662
Acronym / sponsor ID: Pro00051692
Conditions: Poor Thymic Function, Immunodeficiency, Athymia, Immunoreconstitution, Thymus Transplantation, Low T Cell Numbers
Keywords: Cultured Thymus Tissue Implantation
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 11 participants (actual)
Lead sponsor: Sumitomo Pharma Switzerland GmbHIndustry (pharma, biotech, devices)
Study start: Aug 2014 (actual)
Primary completion: Aug 2023 (actual)
Study completion: Aug 2023 (actual)
First posted: 24 Oct 2014 (estimated)
Results: Posted 16 Jan 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Cultured thymus tissue implantation (CTTI)	Experimental	Biological: Cultured Thymus Tissue, Procedure: Blood Draw, Drug: Rabbit Anti-Thymocyte Globulin and Cyclosporine or TacrolimusCultured thymus tissue for the treatment of immunodeficiency and autoimmune disorders

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Cultured Thymus TissueSubjects 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.	Biological	Cultured thymus tissue implantation (CTTI)
Blood DrawAlso: Venipuncture	Procedure or surgery	Cultured thymus tissue implantation (CTTI)
Rabbit Anti-Thymocyte Globulin and Cyclosporine or TacrolimusAlso: RATGAM and Csa or FK506RATGAM 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.	Drug	Cultured thymus tissue implantation (CTTI)

Primary outcome

Survival Rate at End of 1 Year
Time frame: 1 Year
Survival Rate at End of 2 Year
Time frame: 2 Year

Results and safety

Results posted to the registry on 16 Jan 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cultured Thymus Tissue Implantation	11	7

Primary outcome: Survival Rate at End of 1 Year

Time frame: 1 Year. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Cultured Thymus Tissue Implantation n = 11
Value	90.9 (59 to 100)

Population analysed: 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

Primary outcome: Survival Rate at End of 2 Year

Time frame: 2 Year. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Cultured Thymus Tissue Implantation n = 11
Value	87.5 (47 to 100)

Adverse events

Time frame: 2 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cultured Thymus Tissue Implantation	8 of 11 (72.7%)	11 of 11 (100%)	1 of 11

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 17284531Markert 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.
Background: PubMed 20236866Markert 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.
Background: PubMed 15100156Markert 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.
Background: PubMed 18333898Selim 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.
Background: PubMed 18155964Chinn 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.
Background: PubMed 18424759Markert 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.
Background: PubMed 18035553Hudson 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.
Background: PubMed 19066739Markert 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.
Background: PubMed 15100681Markert 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.
BackgroundMarkert 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.
BackgroundMarkert 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.
Background: PubMed 12702512Markert 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John W. Sleasman, M.D. principal investigator

Duke University Medical Center, Pediatrics, Allergy & Immunology

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Survival Rate at End of 1 Year (time frame: 1 Year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02274662, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2025.