AzTrials
AzTrials

DiGeorge AnomalyPhase 1SerumFreeNCT00849888

Serum-Free Thymus Transplantation in DiGeorge Anomaly

A Phase 1 study testing Serum Free Thymus Transplantation with Immunosuppression and Serum Free Thymus Transplantation without immunosuppression in people with DiGeorge Anomaly, run by Sumitomo Pharma Switzerland GmbH.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The study purpose is to determine if thymus tissue cultured in a serum-free (SF) solution is a safe and effective treatment for atypical and typical complete DiGeorge anomaly. [Funding Source - FDA OOPD] Read more about this study

Who is it for?
Ages Up to 2 years
Conditions the study is for
DiGeorge Anomaly
What is being tested?
Serum Free Thymus Transplantation with Immunosuppression and Serum Free Thymus Transplantation without immunosuppression
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
No sites listed yet
Study dates
Apr 2008to Feb 2011
Phase
Phase 1
Are there results?
None posted in the registry

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 Up to 2 years
  • All sexes
  • No healthy volunteers
  • Child

Thymus Recipients Inclusion:

Complete DiGeorge anomaly diagnosis

Must have one of following:

  • congenital heart disease
  • hypocalcemia requiring replacement
  • 22q11 or 10p13 hemizygous
  • CHARGE

Atypical Arm:

  • Must have, or have had, rash. If rash present, skin biopsy must show T cells. If rash resolved, must have >50/cumm T cells; \& <50/cumm naive T cells or <5% total
  • PHA response must be <40000 counts per minute(cpm) on immunosuppression; or, <75000cpm off immunosuppression. PHA test must be done 2x
  • CD45RA+CD62L+ CD3+ T cells must be <50/mm3; or, <5% of total CD3. Test must be done 2x

Typical Arm:

  • PHA response <20 fold or <5,000cpm
  • Circulating CD3+CD45RA+CD62L+T cells <50/mm3 or <5% total T cells
  • 2 tests of T cells \& PHA response must show similar results

Biological Mother Inclusion:

-Must be recipient's biological mother

Thymus Recipient Exclusion:

  • Heart surgery <4 weeks pre-transplant or within 3 months post-transplant
  • Rejection by surgeon or anesthesiologist as surgical candidates
  • Lack of sufficient muscle tissue to accept transplant
  • Medical condition does not allow to undergo a biopsy
  • HIV
  • CMV(>500 copies/ml blood by PCR on 2 tests)
  • Ventilator dependence
  • GVHD
  • Maternal T cells >20% of total T cells
  • Prior immune reconstitution attempts (e.g., BMT, prior thymus transplant)
  • Hypoparathyroidism meeting criteria for combined thymus/parathyroid transplant \& parents desiring it
  • RSV or parainfluenza virus
  • Enterovirus or Adenovirus in stool

Biological Mother Exclusion:

-Unwillingness to sign consent or provide blood/buccal samples

About this study

Official title: Phase I Serum-Free Cultured Thymus Transplantation in DiGeorge Anomaly, IND9836

The study purpose is to determine if thymus tissue cultured in a serum-free (SF) solution is a safe and effective treatment for atypical and typical complete DiGeorge anomaly. [Funding Source - FDA OOPD]

Read the detailed description

Complete DiGeorge anomaly is a congenital disorder characterized by athymia. Without successful treatment, patients remain immunodeficient and usually die by age 2 years. In "typical" complete DiGeorge subjects who have no T cells, thymus transplantation without immunosuppression has resulted in diverse T cell development and good T cell function. In "atypical" complete DiGeorge subjects who have no thymus, a rash, and some T cells that presumably developed extrathymically, thymus transplantation with immunosuppression has resulted in diverse T cell development and good T cell function. Thus far, thymus transplantation studies have used thymus cultured in fetal bovine serum (FBS medium). This protocol's purpose is to determine whether transplanted thymus cultured in serum free medium can safely support thymopoiesis and T cell reconstitution as does FBS medium cultured thymus tissue in DiGeorge anomaly subjects. This protocol includes 2 arms: atypical DiGeorge subjects who will receive immunosuppression and thymus transplantation; and, typical complete DiGeorge subjects who will receive thymus transplantation without immunosuppression. Serum free medium use would reduce concerns of animal product exposure including potential exposure to bovine spongiform encephalopathy(BSE).

Being tested
Serum Free Thymus Transplantation with Immunosuppression, Serum Free Thymus Transplantation without immunosuppression
Keywords
Thymus Transplantation, DiGeorge Anomaly, Athymia, Low T cell numbers, Immunoreconstitution, Immunodeficiency
Medical subject headings
DiGeorge Syndrome, Thymic aplasia, Immunologic Deficiency Syndromes

What participants receive

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

  • Serum Free Thymus Transplantation with ImmunosuppressionBiological

    Also called IND 9836, Thymus Tissue Transplant

    Cyclosporine pre-transplant (trough 180-220ng/ml) until naive T cells develop. Subjects >4,000/cumm T cells, pre-transplant methylprednisolone or prednisolone 1-2mg/kg/day. All subjects pre-transplant days -5,-4,-3: 3 doses 2mg/kg rabbit anti-thymocyte globulin. Thymus tissue (unrelated donor), donor, \& donor's mother screened for safety. Transplant under general anesthesia into quadriceps. First 2 subjects, FBS cultured thymus is transplanted in 1 leg \& serum free (SF) in other. After first 2 subjects >10% naïve T cells, 3rd receives only SF thymus. After 3rd subject >10%naive T cells, 4th subject transplanted. Thymus dose 4-18 grams/m2 body surface area. Thymus biopsy 8-12 weeks post-transplant. Skin biopsy at time of transplant \& thymus biopsy. Followed by immune evaluations.

  • Serum Free Thymus Transplantation without immunosuppressionOther

    Also called IND 9836, Thymus Tissue Transplant

    Thymus tissue (unrelated donor), donor, \& donor's mother screened for safety. Transplant under general anesthesia into quadriceps. First 2 subjects: FBS cultured thymus transplanted in 1 leg \& serum free cultured thymus in other leg. After first 2 subjects have thymopoiesis in serum-free biopsy, >10% naïve T cells, 3rd subject receives only serum free cultured thymus. After 3rd subject >10% naive T cells, 4th subject receives transplant of only serum free cultured thymus. Dose 4-18grams/m2 body surface area. At time of transplant, skin biopsy. Allograft biopsy \& skin biopsy done 8 to 12 weeks post-transplant. (Graft biopsy not done if subject medically unstable.) Post-transplant, subjects followed by immune evaluations, using blood samples, for two years.

Study groups in NCT00849888
Study groupRoleWhat they receive
Atypical Complete DiGeorgeExperimentalThymus Transplantation with Immunosuppression
Receives: Biological: Serum Free Thymus Transplantation with Immunosuppression
Typical Complete DiGeorgeExperimentalThymus Transplantation without Immunosuppression
Receives: Other: Serum Free Thymus Transplantation without immunosuppression

What is being measured

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

  1. Survival

    Survival at one year post thymus transplantation.

    Measured: One year post-thymus transplantation.

  2. Incidence of graft-versus-host-disease (GVHD).

    Development of graft versus host disease in first year after transplantation associated with T cells from the thymus donor.

    Measured: One year post-thymus-transplantation.

  3. Thymopoiesis or graft rejection on biopsy.

    Graft rejection analysis by biopsy at 2 months post-thymus transplantation.

    Measured: Two months post-thymus transplantation.

Secondary outcomes (2)

  1. Incidence of autoimmune disease.

    Incidence of autoimmune disease by year 2 after transplantation Cytopenias as assessed by complete blood counts and differential. Thyroid disease as assessed by thyroid function tests

    Measured: By two years post-thymus transplantation.

  2. Immune outcomes: T cell development; evaluate T cell numbers, diversity, and function.

    Number of naïve CD4 T cells at one year after transplantation Number of total CD4 T cells at one year after transplantation Proliferative response to PHA at one year after transplantation TCRBV diversity by spectratyping measured by DKL score at one year after transplantation

    Measured: One year post-thymus transplantation.

Timeline

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

  1. First posted24 Feb 2009 (estimated)
  2. Study startApr 2008
  3. Primary completionFeb 2011
  4. Study completionFeb 2011

Why it stopped: The sponsor decided to withdraw the study.

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00849888
Sponsor's protocol ID
Pro00006109
Other IDs
1R01FD003528-01, 2R01AI047040-11A2, 5K12HD043494-09, R01AI047040, R01AI054843, R56 Bridge R01AI4704011A1
Acronym
SerumFree
Status last verified
Mar 2022
First submitted
22 Feb 2009
Last updated
1 Apr 2022
Results posted
No
Data monitoring committee
Yes

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, 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

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Serum Free Thymus Transplantation with Immunosuppression and Serum Free Thymus Transplantation without immunosuppression in people with DiGeorge Anomaly, run by Sumitomo Pharma Switzerland GmbH.

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

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Apr 2022. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was stopped early (reason given: The sponsor decided to withdraw the study.). Results are not available in the source record.

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 (time frame: One year post-thymus transplantation.). The study lists 3 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 NCT00849888, which also lists 6 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 1 Apr 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in