Severe Combined ImmunodeficiencyPhase 1/2NCT02127892
SCID Bu/Flu/ATG Study With T Cell Depletion
A Phase 1/2 study testing unrelated BM with T cell depletion, unrelated cord blood and haplo BM with T cell depletion in people with Severe Combined Immunodeficiency, run by Neena Kapoor, M.D. at 1 site in United States.
Trial summary
This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with a diagnosis of Severe Combined Immune Deficiency (SCID) who do not have an HLA-matched sibling donor. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Severe Combined Immunodeficiency
- What is being tested?
- unrelated BM with T cell depletion, unrelated cord blood and haplo BM with T cell depletion
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jan 2007to 1 Aug 2016
- Phase
- Phase 1/2
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients with SCID who lack a histocompatible sibling or HLA-matched related donor will be considered as candidates for this study protocol.
- Eligible patients must have adequate physical function to tolerate the chemotherapy conditioning regimen and the HSCT, as measure by:
- Renal: creatinine clearance or GFR ≥50 ml/min/1.73m2, and not requiring dialysis
- Pulmonary: Because patients with SCID frequently present with infectious pneumonia causing ventilatory failure, patients will be considered for enrollment in the study even if respiratory failure requiring mechanical ventilatory support is present. In patients recently diagnosed with pneumonia, efforts to stabilize the respiratory status will be made prior to enrollment in the study.
- Infectious disease status. The presence of infection per se will not be a reason for exclusion from the study. Patients with SCID are frequently infected with both routine pathogens as well as opportunistic infections. Antibiotic, antifungal and antiviral prophylaxis and therapy will be instituted as clinically indicated. Despite the use of antimicrobial therapy, the ability to control infections will not be achieved unless HSCT is performed. Therefore, subjects may be enrolled in the study, even though infection is present, because control of infection may depend on engraftment of a donor immune system.
- Patients will be 0-21 years of age.
Who cannot join
- Patient with histocompatible sibling or other related donor
- End-organ failure that precludes the ability to tolerate the transplant procedure, including conditioning.
- Renal failure requiring dialysis
- Congenital heart disease resulting in congestive heart failure
- Severe CNS disease, e.g., coma or intractable seizures
- Ventilatory failure due to non-infectious etiology
Show all 10Show fewer
- Major congenital anomalies that adversely affect survival, eg CNS malformations
- Metabolic diseases that would affect transplant survival, eg urea cycle disorders
- HIV infection
- Since the only chance of survival for patients with SCID is successful transplantation, all patients with SCID will be considered to be potential subjects for the study, regardless of end-organ dysfunction.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Los Angeles
Los Angeles, California, 90027
About this study
Official title: Phase I/II Trial of Hematopoietic Stem Cell Transplant (HSCT) for Children With Severe Combined Immune Deficiency (SCID) and Without an HLA-Matched Sibling Donor
This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with a diagnosis of Severe Combined Immune Deficiency (SCID) who do not have an HLA-matched sibling donor. The stem cells will be derived from a 1) matched unrelated donor (MUD), 2) unrelated cord blood donor, or 3) a haplo-identical (parental) donor (in descending order of preference).Patients will receive a novel conditioning regimen with Busulfan, Fludarabine and Anti-thymocyte globulin (ATG) followed by an unrelated donor hematopoietic stem cell transplant (HSCT) with T-cell depletion using the CliniMACS device.
Read the detailed description
The study is being conducted to assess the following:
- overall survival
- event-free survival (events are defined as: death,non-engraftment/2nd transplant, immune reconstitution failure)
- acute toxicity of the conditioning regimen
- engraftment frequency immune reconstitution frequency and tempo acute and chronic graft-versus-host disease (GVHD), frequency and severity.
The outcome from this protocol will be compared to the retrospective cohort consisting of all patients who have undergone haplo-identical HSCT for SCID at CHLA from 1984-2006 based on the assessment of the above-listed endpoints.
The CliniMACS device will be used for CD34+ selection in place of the Isolex 300i. The CliniMACS CD34 Reagent System is an investigational medical device that has not yet been approved by the FDA. This device is used in vitro to select and enrich specific cell populations. When using the CliniMACS CD34 Reagent, the system selects CD34+ cells from heterogenous hematological cell populations for transplantation in cases where this is clinically indicated.
- Conditions
- Severe Combined Immunodeficiency
- Being tested
- unrelated BM with T cell depletion, unrelated cord blood, haplo BM with T cell depletion, unrelated PBSC with T cell depletion
- Keywords
- Severe Combined Immune Deficiency, SCID, HLA-matched unrelated donor, unrelated, MUD, bone marrow, cord blood, haplo-identical, peripheral blood, CD34+ selection, T cell depletion, HSCT, BMT, CliniMACS
- Medical subject headings
- Severe Combined Immunodeficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
unrelated BM with T cell depletionBiological
Also called CD34+ selection using CliniMACS
Remaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted).
unrelated cord bloodBiological
Also called umbilical cord blood
Cord blood will be thawed (and processed if ABO incompatibility) per institutional SOP.
haplo BM with T cell depletionBiological
Also called CD34+ selection with CliniMACS
haplo-identical (parental) bone marrow will be processed for CD34+ cell isolation.
unrelated PBSC with T cell depletionDevice
Also called CD34+ selection using CliniMACS
peripheral blood stem cell will be processed for CD34+ cell isolation.
| Study group | Role | What they receive |
|---|---|---|
| unrelated BM with T cell depletion | Other | Acceptable matching for matched unrelated donor (MUD) bone marrow will be genotypic matches at 10 of 10 HLA alleles (HLA-A, B, C, DR and DQ) or 9 of 10 HLA alleles. Receives: Biological: unrelated BM with T cell depletion |
| unrelated cord blood | Other | Acceptable matching for unrelated cord blood will be a genotypic match at 6 of 6 alleles (HLA A, B and DR) or 5 of 6 alleles, but not with mismatches at both alleles of a single locus (e.g. not mismatched for both HLA A alleles). Receives: Biological: unrelated cord blood |
| haplo BM with T cell depletion | Other | If there is no unrelated donor available meeting the matching criteria for unrelated bone marrow or unrelated cord blood donors. Receives: Biological: haplo BM with T cell depletion |
| unrelated PBSC with T cell depletion | Other | The preferred source will be bone marrow, however, if a donor is unable or unwilling to donate bone marrow, peripheral blood stem cells (PBSC) will be allowed. Receives: Device: unrelated PBSC with T cell depletion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Engraftment
Engraftment is defined as recovery of blood counts (neutrophil and platelet engraftment) with cells of donor origin, documented by either bone marrow or peripheral blood chimerism assays after hematopoietic stem cell transplant.
Measured: 100 day
Secondary outcomes (1)
Number of Participants With Donor-derived CD3+ T Lymphocytes >/= 100/mm3
Absolute number of donor-derived CD3+ T lymphocytes >/= 100/mm3 in participating subjects.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2014 (estimated)
- Study start2 Jan 2007
- Primary completion1 Aug 2016
- Study completion1 Aug 2016
Why it stopped: Closed due to slow accrual. Nine subjects enrolled over 7 years.
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.
- Other trials for Severe Combined ImmunodeficiencyStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neena Kapoor, M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Neena Kapoor, M.D., Children's Hospital Los Angeles
- Investigators
- Neena Kapoor, M.D., Principal investigator, Children's Hospital Los Angeles, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02127892
- Sponsor's protocol ID
- CCI-06-00243
- Status last verified
- Aug 2017
- First submitted
- 19 Oct 2012
- Last updated
- 18 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Hematopoietic Stem Cell Transplant (HSCT) for Children With Severe Combined Immune Deficiency (SCID) and Without an HLA-Matched Sibling Donor
- ClinicalTrials.gov ID
- NCT02127892
- Acronym / sponsor ID
- CCI-06-00243
- Conditions
- Severe Combined Immunodeficiency
- Keywords
- Severe Combined Immune Deficiency, SCID, HLA-matched unrelated donor, unrelated, MUD, bone marrow, cord blood, haplo-identical
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed due to slow accrual. Nine subjects enrolled over 7 years.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Neena Kapoor, M.D.University, hospital or other
- Study start
- 2 Jan 2007 (actual)
- Primary completion
- 1 Aug 2016 (actual)
- Study completion
- 1 Aug 2016 (actual)
- First posted
- 1 May 2014 (estimated)
- Results
- Posted 18 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with a diagnosis of Severe Combined Immune Deficiency (SCID) who do not have an HLA-matched sibling donor. The stem cells will be derived from a 1) matched unrelated donor (MUD), 2) unrelated cord blood donor, or 3) a haplo-identical (parental) donor (in descending order of preference).Patients will receive a novel conditioning regimen with Busulfan, Fludarabine and Anti-thymocyte globulin (ATG) followed by an unrelated donor hematopoietic stem cell transplant (HSCT) with T-cell depletion using the CliniMACS device.
Detailed description
The study is being conducted to assess the following:
- overall survival
- event-free survival (events are defined as: death,non-engraftment/2nd transplant, immune reconstitution failure)
- acute toxicity of the conditioning regimen
- engraftment frequency immune reconstitution frequency and tempo acute and chronic graft-versus-host disease (GVHD), frequency and severity.
The outcome from this protocol will be compared to the retrospective cohort consisting of all patients who have undergone haplo-identical HSCT for SCID at CHLA from 1984-2006 based on the assessment of the above-listed endpoints.
The CliniMACS device will be used for CD34+ selection in place of the Isolex 300i. The CliniMACS CD34 Reagent System is an investigational medical device that has not yet been approved by the FDA. This device is used in vitro to select and enrich specific cell populations. When using the CliniMACS CD34 Reagent, the system selects CD34+ cells from heterogenous hematological cell populations for transplantation in cases where this is clinically indicated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| unrelated BM with T cell depletion | Other | Biological: unrelated BM with T cell depletionAcceptable matching for matched unrelated donor (MUD) bone marrow will be genotypic matches at 10 of 10 HLA alleles (HLA-A, B, C, DR and DQ) or 9 of 10 HLA alleles. |
| unrelated cord blood | Other | Biological: unrelated cord bloodAcceptable matching for unrelated cord blood will be a genotypic match at 6 of 6 alleles (HLA A, B and DR) or 5 of 6 alleles, but not with mismatches at both alleles of a single locus (e.g. not mismatched for both HLA A alleles). |
| haplo BM with T cell depletion | Other | Biological: haplo BM with T cell depletionIf there is no unrelated donor available meeting the matching criteria for unrelated bone marrow or unrelated cord blood donors. |
| unrelated PBSC with T cell depletion | Other | Device: unrelated PBSC with T cell depletionThe preferred source will be bone marrow, however, if a donor is unable or unwilling to donate bone marrow, peripheral blood stem cells (PBSC) will be allowed. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- All patients with SCID who lack a histocompatible sibling or HLA-matched related donor will be considered as candidates for this study protocol.
- Eligible patients must have adequate physical function to tolerate the chemotherapy conditioning regimen and the HSCT, as measure by:
Key exclusion criteria (10 listed)
- Patient with histocompatible sibling or other related donor
- End-organ failure that precludes the ability to tolerate the transplant procedure, including conditioning.
- Renal failure requiring dialysis
- Congenital heart disease resulting in congestive heart failure
- Severe CNS disease, e.g., coma or intractable seizures
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 |
|---|---|---|
| unrelated BM with T cell depletionAlso: CD34+ selection using CliniMACSRemaining unmanipulated bone marrow will be processed to isolate CD34+ cells (T cell depleted). | Biological | unrelated BM with T cell depletion |
| unrelated cord bloodAlso: umbilical cord bloodCord blood will be thawed (and processed if ABO incompatibility) per institutional SOP. | Biological | unrelated cord blood |
| haplo BM with T cell depletionAlso: CD34+ selection with CliniMACShaplo-identical (parental) bone marrow will be processed for CD34+ cell isolation. | Biological | haplo BM with T cell depletion |
| unrelated PBSC with T cell depletionAlso: CD34+ selection using CliniMACSperipheral blood stem cell will be processed for CD34+ cell isolation. | Device | unrelated PBSC with T cell depletion |
Primary outcome
Number of Participants With Engraftment
Time frame: 100 day
Engraftment is defined as recovery of blood counts (neutrophil and platelet engraftment) with cells of donor origin, documented by either bone marrow or peripheral blood chimerism assays after hematopoietic stem cell transplant.
1 secondary outcome
Number of Participants With Donor-derived CD3+ T Lymphocytes >/= 100/mm3
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Neena Kapoor, M.D. principal investigator
Children's Hospital Los Angeles, University of Southern California
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 unrelated BM with T cell depletion, unrelated cord blood and haplo BM with T cell depletion in people with Severe Combined Immunodeficiency, run by Neena Kapoor, M.D. 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 6 inclusion and 10 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: stopped early, as of the sponsor's last update on 18 Sep 2017. 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?
Yes. Results are posted in the registry (first posted 18 Sep 2017). 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?
Number of Participants With Engraftment (time frame: 100 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Sep 2017; AzTrials last refreshed its copy on 26 Oct 2026.