CD40L-HyperIgM SyndromePhase 1/2NCT06959771
Base Editing Hematopoietic Stem Cell and T Cell Gene Therapy for CD40L-HyperIgM Syndrome: Single Patient Study
A Phase 1/2 study testing Base-edited hematopoietic stem and progenitor cells, Alemtuzumab and Sirolimus in people with CD40L-HyperIgM Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: X-linked hyper-IgM (HIGM) syndrome is caused by a mutation in the CD40 ligand (CD40L) gene. People with this disease have white blood cells that do not work properly. These people are at risk of severe infections and autoimmune diseases. Read more about this study
- Who is it for?
- Ages 37 to 120 years, men only
- Conditions the study is for
- CD40L-HyperIgM Syndrome
- What is being tested?
- Base-edited hematopoietic stem and progenitor cells, Alemtuzumab and Sirolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jul 2025to 28 Oct 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 37 to 120 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- This study is a single participant research study and to receive the study product, he needs to meet the following criteria:
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Has CD40L Q220X mutation
- Defective class switching
- Liver abnormalities (transaminases>UL)
Show all 11Show fewer
- Portal hypertension
- Consensus from Hepatology Consult to receive myeloid conditioning
- Ability to take oral medication and be willing to adhere to the intervention regimen
- Use of condoms or other methods to ensure effective contraception with partner
- Ability of subject to understand and the willingness to sign a written informed consent document
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Known allergic reactions to components of the BE HSPC study product or BE T cell product
- Febrile illness within two weeks of hospital admission for treatment
- Unwilling to submit their information as part of the alemtuzumab (Campath(R)) Distribution Program application or the Distribution Program committee has determined the participant is not qualified to receive alemtuzumab.
- NOTE: Alemtuzumab (campath) (IV formulation) is no longer distributed commercially. To receive product, the physician must contact the program for the participant. If the participant is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore no transplant will occur on this protocol. http://www.campath.com/
- Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies and NIH protocols 94-I-0073 and 05-I-0213. Consideration for coenrollment in trials evaluating the use of a licensed medication will require the approval of the principal investigator in consultation with the medical monitor. Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the principal investigator (in consultation with the medical monitor).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Suk De Ravin, MD, PhD, 301-496-6772, sderavin@niaid.nih.gov
NIH Clinical Center Office of Patient Recruitment (OPR), (800) 411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Base Editing Hematopoietic Stem Cell and BE T Cell Gene Therapy for CD40L-HyperIgM Syndrome-Single Patient Study
Background:
X-linked hyper-IgM (HIGM) syndrome is caused by a mutation in the CD40 ligand (CD40L) gene. People with this disease have white blood cells that do not work properly. These people are at risk of severe infections and autoimmune diseases. Researchers want to know if these base-edited stem cells and T cells can help people with CD40L-HIGM syndrome.
Read more
Objective:
To test base-edited stem cells and base-edited T cells in 1 person with CD40L-HIGM syndrome.
Eligibility:
A single male with CD40L-HIGM syndrome.
Design:
A single participant is planned to receive a single dose of edited stem cells and supportive treatment with edited T cells. Participant stem and T cells will undergo base editing to repair the mutation.
In preparation for the gene therapy, the participant will receive busulfan chemotherapy and alemtuzumab. After treatment, the participant will have follow-up visits every few months in the first 2 years after treatment. Long-term visits will continue annually for 15 years.
Read the detailed description
Study Description:
This is a single participant gene therapy study to provide a participant with CD40L c.658C>T; p.Q220X-Hyper IgM syndrome with autologous base-edited hematopoietic stem/progenitor cells (HSPC) and base-edited T cells (BE T). The study hypothesis is that base edited HSPCs will be repaired efficiently and safely to restore CD40L expression and improve immune function long term. BE T cells will provide functional T cells to support subject against immunodeficiency and lymphopenia.
The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning using busulfan administered once daily for 2 days with a daily target AUC of 4500 micromol*min/L or a cumulative AUC of 9000 micromol*min/L (approximately 6 mg/kg) and serotherapy (alemtuzumab (Campath)) 10 mg/m^2 total dose divided over 3 days by subcutaneous injection on days -21, -20, and -19. Following infusion, the participant will be evaluated at months 3, 6, 9, 12, 18, 24. Long-term annual follow up will be performed on a separate protocol.
Base edited autologous T cells will be administered at 2 weeks following BE HSPC infusion that function as 'donor lymphocyte infusions' to protect the patient from the diseaserelated T-cell immunodeficiency and alemtuzumab-related lymphopenia. Subsequent doses of BE T cells may be infused monthly as indicated to achieve T cell reconstitution for treatment of infections.
Objectives:
- Primary Objective: To determine the safety and efficacy of BE HSPC CD40L and BE T cells.
- Secondary Objectives: To determine restoration of CD40L expression and immune function
- Exploratory Objectives:
- Assess for potential unintended edits
- Kinetics of immune reconstitution
Endpoints:
- Primary Endpoint:
- Efficacy determined by percentages of corrected alleles
- Safety determined by toxicities related to infusion of Study Cell Product
- Secondary Endpoints:
- Level of CD40L expression in peripheral blood T cells
- IgG production
- Response to immunization
- Exploratory Endpoints:
- Repeat WES at 24 months after study cell product infusion
- Evaluate for gene correction levels in peripheral blood CD34s and isolated immune cell lineages
- Conditions
- CD40L-HyperIgM Syndrome
- Being tested
- Base-edited hematopoietic stem and progenitor cells, Alemtuzumab, Sirolimus, Palifermin, Busulfan
- Keywords
- base editing, Gene Editing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Base-edited hematopoietic stem and progenitor cellsBiological
The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning.
AlemtuzumabDrug
Serotherapy agent, 10 mg/m^2 on days -21, -20 and -19
SirolimusDrug
Immunophilin drug, will start on day -1, targeting a trough level between 4-12 ng/mL.
PaliferminDrug
Mucositis prophylaxis agent, will be administered at 60 mcg/kg/day for 3 days before initiation of busulfan (days -6 to -4), as well as for the 3 days following study agent administration (days 1 to 3).
BusulfanDrug
Myeloid conditioning agent, administered once daily (3 mg/kg) x 2 days, targeting a daily AUC of 4500 micromol*min/L or a cumulative AUC of 9000 micromol*min/L for the 2 days of therapy, if levels are available
Base-edited T lymphocyte cellsBiological
The secondary study cell product is base edited autologous which will be administered as a one-time infusion two weeks following the infusion of the base-edited autologous HSPCs.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm Study | Experimental | The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following conditioning using busulfan and alemtuzumab. Receives: Biological: Base-edited hematopoietic stem and progenitor cells; Drug: Alemtuzumab; Drug: Sirolimus; Drug: Palifermin; Drug: Busulfan; Biological: Base-edited T lymphocyte cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety determined by toxicities related to the infusion of the Study Cell Products
To determine the safety and efficacy of BE HSPC CD40L and BE T Cells
Measured: Through end of study
Efficacy determined by percentages of corrected alleles
To determine the safety and efficacy of BE HSPC CD40L and BE T Cells
Measured: Through end of study
Secondary outcomes (3)
Level of CD40L expression in peripheral blood T cells
To determine restoration of CD40L expression and immune function
Measured: Through end of study
IgG production
To determine restoration of CD40L expression and immune function
Measured: Through end of study
Response to immunization
To determine restoration of CD40L expression and immune function
Measured: Through end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2025
- Study start16 Jul 2025
- Primary completion28 Oct 2027 (estimated)
- Study completion28 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for CD40L-HyperIgM SyndromeStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Suk S De Ravin, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06959771
- Sponsor's protocol ID
- 10002385
- Other IDs
- 002385-I
- Status last verified
- 29 Jul 2026
- First submitted
- 6 May 2025
- Last updated
- 31 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, Stiehm ER, Conley ME. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore). 2003 Nov;82(6):373-84. doi: 10.1097/01.md.0000100046.06009.b0.
PubMed 14663287Kracker S, Gardes P, Durandy A. Inherited defects of immunoglobulin class switch recombination. Adv Exp Med Biol. 2010;685:166-74. doi: 10.1007/978-1-4419-6448-9_15.
PubMed 20687504Hubbard N, Hagin D, Sommer K, Song Y, Khan I, Clough C, Ochs HD, Rawlings DJ, Scharenberg AM, Torgerson TR. Targeted gene editing restores regulated CD40L function in X-linked hyper-IgM syndrome. Blood. 2016 May 26;127(21):2513-22. doi: 10.1182/blood-2015-11-683235. Epub 2016 Feb 22.
PubMed 26903548Ferrari S, Vavassori V, Canarutto D, Jacob A, Castiello MC, Javed AO, Genovese P. Gene Editing of Hematopoietic Stem Cells: Hopes and Hurdles Toward Clinical Translation. Front Genome Ed. 2021 Mar 31;3:618378. doi: 10.3389/fgeed.2021.618378. eCollection 2021.
PubMed 34713250Lazzarotto CR, Katta V, Li Y, Urbina E, Lee G, Tsai SQ. CHANGE-seq-BE enables simultaneously sensitive and unbiased in vitro profiling of base editor genome-wide activity. bioRxiv [Preprint]. 2024 Mar 30:2024.03.28.586621. doi: 10.1101/2024.03.28.586621.
PubMed 38585919de la Morena MT, Leonard D, Torgerson TR, Cabral-Marques O, Slatter M, Aghamohammadi A, Chandra S, Murguia-Favela L, Bonilla FA, Kanariou M, Damrongwatanasuk R, Kuo CY, Dvorak CC, Meyts I, Chen K, Kobrynski L, Kapoor N, Richter D, DiGiovanni D, Dhalla F, Farmaki E, Speckmann C, Espanol T, Shcherbina A, Hanson IC, Litzman J, Routes JM, Wong M, Fuleihan R, Seneviratne SL, Small TN, Janda A, Bezrodnik L, Seger R, Raccio AG, Edgar JD, Chou J, Abbott JK, van Montfrans J, Gonzalez-Granado LI, Bunin N, Kutukculer N, Gray P, Seminario G, Pasic S, Aquino V, Wysocki C, Abolhassani H, Dorsey M, Cunningham-Rundles C, Knutsen AP, Sleasman J, Costa Carvalho BT, Condino-Neto A, Grunebaum E, Chapel H, Ochs HD, Filipovich A, Cowan M, Gennery A, Cant A, Notarangelo LD, Roifman CM. Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation. J Allergy Clin Immunol. 2017 Apr;139(4):1282-1292. doi: 10.1016/j.jaci.2016.07.039. Epub 2016 Sep 30.
PubMed 27697500Gennery AR, Khawaja K, Veys P, Bredius RG, Notarangelo LD, Mazzolari E, Fischer A, Landais P, Cavazzana-Calvo M, Friedrich W, Fasth A, Wulffraat NM, Matthes-Martin S, Bensoussan D, Bordigoni P, Lange A, Pagliuca A, Andolina M, Cant AJ, Davies EG. Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002. Blood. 2004 Feb 1;103(3):1152-7. doi: 10.1182/blood-2003-06-2014. Epub 2003 Oct 2.
PubMed 14525761Vavassori V, Mercuri E, Marcovecchio GE, Castiello MC, Schiroli G, Albano L, Margulies C, Buquicchio F, Fontana E, Beretta S, Merelli I, Cappelleri A, Rancoita PM, Lougaris V, Plebani A, Kanariou M, Lankester A, Ferrua F, Scanziani E, Cotta-Ramusino C, Villa A, Naldini L, Genovese P. Modeling, optimization, and comparable efficacy of T cell and hematopoietic stem cell gene editing for treating hyper-IgM syndrome. EMBO Mol Med. 2021 Mar 5;13(3):e13545. doi: 10.15252/emmm.202013545. Epub 2021 Jan 21.
PubMed 33475257
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Base Editing Hematopoietic Stem Cell and BE T Cell Gene Therapy for CD40L-HyperIgM Syndrome-Single Patient Study
- ClinicalTrials.gov ID
- NCT06959771
- Acronym / sponsor ID
- 10002385
- Conditions
- CD40L-HyperIgM Syndrome
- Keywords
- base editing, Gene Editing
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 16 Jul 2025 (actual)
- Primary completion
- 28 Oct 2027 (estimated)
- Study completion
- 28 Oct 2027 (estimated)
- First posted
- 7 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
X-linked hyper-IgM (HIGM) syndrome is caused by a mutation in the CD40 ligand (CD40L) gene. People with this disease have white blood cells that do not work properly. These people are at risk of severe infections and autoimmune diseases. Researchers want to know if these base-edited stem cells and T cells can help people with CD40L-HIGM syndrome.
Objective:
To test base-edited stem cells and base-edited T cells in 1 person with CD40L-HIGM syndrome.
Eligibility:
A single male with CD40L-HIGM syndrome.
Design:
A single participant is planned to receive a single dose of edited stem cells and supportive treatment with edited T cells. Participant stem and T cells will undergo base editing to repair the mutation.
In preparation for the gene therapy, the participant will receive busulfan chemotherapy and alemtuzumab. After treatment, the participant will have follow-up visits every few months in the first 2 years after treatment. Long-term visits will continue annually for 15 years.
Detailed description
Study Description:
This is a single participant gene therapy study to provide a participant with CD40L c.658C>T; p.Q220X-Hyper IgM syndrome with autologous base-edited hematopoietic stem/progenitor cells (HSPC) and base-edited T cells (BE T). The study hypothesis is that base edited HSPCs will be repaired efficiently and safely to restore CD40L expression and improve immune function long term. BE T cells will provide functional T cells to support subject against immunodeficiency and lymphopenia.
The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning using busulfan administered once daily for 2 days with a daily target AUC of 4500 micromol*min/L or a cumulative AUC of 9000 micromol*min/L (approximately 6 mg/kg) and serotherapy (alemtuzumab (Campath)) 10 mg/m^2 total dose divided over 3 days by subcutaneous injection on days -21, -20, and -19. Following infusion, the participant will be evaluated at months 3, 6, 9, 12, 18, 24. Long-term annual follow up will be performed on a separate protocol.
Base edited autologous T cells will be administered at 2 weeks following BE HSPC infusion that function as 'donor lymphocyte infusions' to protect the patient from the diseaserelated T-cell immunodeficiency and alemtuzumab-related lymphopenia. Subsequent doses of BE T cells may be infused monthly as indicated to achieve T cell reconstitution for treatment of infections.
Objectives:
- Primary Objective: To determine the safety and efficacy of BE HSPC CD40L and BE T cells.
- Secondary Objectives: To determine restoration of CD40L expression and immune function
- Exploratory Objectives:
- Assess for potential unintended edits
- Kinetics of immune reconstitution
Endpoints:
- Primary Endpoint:
- Efficacy determined by percentages of corrected alleles
- Safety determined by toxicities related to infusion of Study Cell Product
- Secondary Endpoints:
- Level of CD40L expression in peripheral blood T cells
- IgG production
- Response to immunization
- Exploratory Endpoints:
- Repeat WES at 24 months after study cell product infusion
- Evaluate for gene correction levels in peripheral blood CD34s and isolated immune cell lineages
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm Study | Experimental | Biological: Base-edited hematopoietic stem and progenitor cells, Drug: Alemtuzumab, Drug: Sirolimus, Drug: Palifermin, Drug: Busulfan, Biological: Base-edited T lymphocyte cellsThe study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following conditioning using busulfan and alemtuzumab. |
Who may qualify
- Ages
- 37 to 120 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- This study is a single participant research study and to receive the study product, he needs to meet the following criteria:
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Has CD40L Q220X mutation
- Defective class switching
Key exclusion criteria (6 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Known allergic reactions to components of the BE HSPC study product or BE T cell product
- Febrile illness within two weeks of hospital admission for treatment
- Unwilling to submit their information as part of the alemtuzumab (Campath(R)) Distribution Program application or the Distribution Program committee has determined the participant is not qualified to receive alemtuzumab.
- NOTE: Alemtuzumab (campath) (IV formulation) is no longer distributed commercially. To receive product, the physician must contact the program for the participant. If the participant is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore no transplant will occur on this protocol. http://www.campath.com/
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 |
|---|---|---|
| Base-edited hematopoietic stem and progenitor cellsThe study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning. | Biological | Single Arm Study |
| AlemtuzumabSerotherapy agent, 10 mg/m^2 on days -21, -20 and -19 | Drug | Single Arm Study |
| SirolimusImmunophilin drug, will start on day -1, targeting a trough level between 4-12 ng/mL. | Drug | Single Arm Study |
| PaliferminMucositis prophylaxis agent, will be administered at 60 mcg/kg/day for 3 days before initiation of busulfan (days -6 to -4), as well as for the 3 days following study agent administration (days 1 to 3). | Drug | Single Arm Study |
| BusulfanMyeloid conditioning agent, administered once daily (3 mg/kg) x 2 days, targeting a daily AUC of 4500 micromol*min/L or a cumulative AUC of 9000 micromol*min/L for the 2 days of therapy, if levels are available | Drug | Single Arm Study |
| Base-edited T lymphocyte cellsThe secondary study cell product is base edited autologous which will be administered as a one-time infusion two weeks following the infusion of the base-edited autologous HSPCs. | Biological | Single Arm Study |
Primary outcome
Safety determined by toxicities related to the infusion of the Study Cell Products
Time frame: Through end of study
To determine the safety and efficacy of BE HSPC CD40L and BE T Cells
Efficacy determined by percentages of corrected alleles
Time frame: Through end of study
To determine the safety and efficacy of BE HSPC CD40L and BE T Cells
3 secondary outcomes
Level of CD40L expression in peripheral blood T cells
Time frame: Through end of study
IgG production
Time frame: Through end of study
Response to immunization
Time frame: Through end of study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- Background: PubMed 14663287Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, Stiehm ER, Conley ME. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore). 2003 Nov;82(6):373-84. doi: 10.1097/01.md.0000100046.06009.b0.
- Background: PubMed 20687504Kracker S, Gardes P, Durandy A. Inherited defects of immunoglobulin class switch recombination. Adv Exp Med Biol. 2010;685:166-74. doi: 10.1007/978-1-4419-6448-9_15.
- Background: PubMed 26903548Hubbard N, Hagin D, Sommer K, Song Y, Khan I, Clough C, Ochs HD, Rawlings DJ, Scharenberg AM, Torgerson TR. Targeted gene editing restores regulated CD40L function in X-linked hyper-IgM syndrome. Blood. 2016 May 26;127(21):2513-22. doi: 10.1182/blood-2015-11-683235. Epub 2016 Feb 22.
- Background: PubMed 34713250Ferrari S, Vavassori V, Canarutto D, Jacob A, Castiello MC, Javed AO, Genovese P. Gene Editing of Hematopoietic Stem Cells: Hopes and Hurdles Toward Clinical Translation. Front Genome Ed. 2021 Mar 31;3:618378. doi: 10.3389/fgeed.2021.618378. eCollection 2021.
- Background: PubMed 38585919Lazzarotto CR, Katta V, Li Y, Urbina E, Lee G, Tsai SQ. CHANGE-seq-BE enables simultaneously sensitive and unbiased in vitro profiling of base editor genome-wide activity. bioRxiv [Preprint]. 2024 Mar 30:2024.03.28.586621. doi: 10.1101/2024.03.28.586621.
- Background: PubMed 27697500de la Morena MT, Leonard D, Torgerson TR, Cabral-Marques O, Slatter M, Aghamohammadi A, Chandra S, Murguia-Favela L, Bonilla FA, Kanariou M, Damrongwatanasuk R, Kuo CY, Dvorak CC, Meyts I, Chen K, Kobrynski L, Kapoor N, Richter D, DiGiovanni D, Dhalla F, Farmaki E, Speckmann C, Espanol T, Shcherbina A, Hanson IC, Litzman J, Routes JM, Wong M, Fuleihan R, Seneviratne SL, Small TN, Janda A, Bezrodnik L, Seger R, Raccio AG, Edgar JD, Chou J, Abbott JK, van Montfrans J, Gonzalez-Granado LI, Bunin N, Kutukculer N, Gray P, Seminario G, Pasic S, Aquino V, Wysocki C, Abolhassani H, Dorsey M, Cunningham-Rundles C, Knutsen AP, Sleasman J, Costa Carvalho BT, Condino-Neto A, Grunebaum E, Chapel H, Ochs HD, Filipovich A, Cowan M, Gennery A, Cant A, Notarangelo LD, Roifman CM. Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation. J Allergy Clin Immunol. 2017 Apr;139(4):1282-1292. doi: 10.1016/j.jaci.2016.07.039. Epub 2016 Sep 30.
- Background: PubMed 14525761Gennery AR, Khawaja K, Veys P, Bredius RG, Notarangelo LD, Mazzolari E, Fischer A, Landais P, Cavazzana-Calvo M, Friedrich W, Fasth A, Wulffraat NM, Matthes-Martin S, Bensoussan D, Bordigoni P, Lange A, Pagliuca A, Andolina M, Cant AJ, Davies EG. Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002. Blood. 2004 Feb 1;103(3):1152-7. doi: 10.1182/blood-2003-06-2014. Epub 2003 Oct 2.
- Background: PubMed 33475257Vavassori V, Mercuri E, Marcovecchio GE, Castiello MC, Schiroli G, Albano L, Margulies C, Buquicchio F, Fontana E, Beretta S, Merelli I, Cappelleri A, Rancoita PM, Lougaris V, Plebani A, Kanariou M, Lankester A, Ferrua F, Scanziani E, Cotta-Ramusino C, Villa A, Naldini L, Genovese P. Modeling, optimization, and comparable efficacy of T cell and hematopoietic stem cell gene editing for treating hyper-IgM syndrome. EMBO Mol Med. 2021 Mar 5;13(3):e13545. doi: 10.15252/emmm.202013545. Epub 2021 Jan 21.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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.
Suk S De Ravin, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Base-edited hematopoietic stem and progenitor cells, Alemtuzumab and Sirolimus in people with CD40L-HyperIgM Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. 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: looking for participants now, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Suk S De Ravin, M.D. ((301) 496-6772, sderavin@niaid.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety determined by toxicities related to the infusion of the Study Cell Products (time frame: Through end of study). 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 NCT06959771, which also lists 8 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 31 Jul 2026; AzTrials last refreshed its copy on 31 Oct 2026.