Primary Immune Deficiency DisorderPhase 2/3NCT02327351
TCR Alpha/Beta Depletion for HSCT From Haploidentical and Unrelated Donors in the Treatment of PID
A Phase 2/3 study testing Biological: TCR alfa beta T cell depletion in people with Primary Immune Deficiency Disorder and Hematopoietic Stem Cell Transplantation, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
Trial summary
Treatment Study to assess of safety and efficiency of T cells receptor (TCR) alfa beta depleted graft for hematopoietic stem cell transplantation (HSCT) from haploidentical and unrelated donors in patients with primary immunodeficiency diseases Read more about this study
- Who is it for?
- Ages 1 month to 18 years
- Conditions the study is for
- Primary Immune Deficiency Disorder, Hematopoietic Stem Cell Transplantation
- What is being tested?
- Biological: TCR alfa beta T cell depletion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 1 siteRussia
- Study dates
- Jul 2012to Jun 2018
- Phase
- Phase 2/3
- 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 1 month to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients aged ≥ 1 months and < 19 years
- Patients diagnosed with Primary Immunodeficiency Diseases eligible for an allogeneic transplantation and lacking a related HLA-matched donor
- Lansky/Karnofsky score > 40, WHO > 4
- Signed written informed consent
Who cannot join
- Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 ml / min)
- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction <40%)
- Serious concurrent uncontrolled medical disorder
- Pregnant or breast feeding female patient
- Lack of parents' informed consent.
Trial locations and contacts
1 site in 1 country.
Russia1 site
Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
Moscow, 117997
About this study
Official title: Phase II/III Study of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated and Haploidentical Donors After TCR Alfa Beta Negative Selection in Pediatric Patients With Primary Immunodeficiency Diseases
Treatment Study to assess of safety and efficiency of T cells receptor (TCR) alfa beta depleted graft for hematopoietic stem cell transplantation (HSCT) from haploidentical and unrelated donors in patients with primary immunodeficiency diseases
Read the detailed description
Infections, graft versus host diseases (GVHD) and associated morbidity and mortality remains significant problems after unrelated and haploidentical hematopoietic stem sell transplantation (HSCT) in patients with primary immunodeficiency diseases (PID). In this study the hypothesis is that the transplantation of TCR alfa beta depleted peripheral blood stem cells (PBSC) would offers advantages over the use of positively selected CD34+ stem cells in haploidentical HSCT and non-manipulated graft in unrelated HSCT.
The purpose of this study is to evaluate the safety and efficiency of the selective infusion of TCR alfa beta T cell depleted graft in pediatric patients with PID receiving HSCT from haploidentical and unrelated donors.
- Being tested
- Biological: TCR alfa beta T cell depletion
- Medical subject headings
- Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological: TCR alfa beta T cell depletionOther
| Study group | Role | What they receive |
|---|---|---|
| TCR alfa beta depletion | Experimental | TCR alfa beta depleted graft, infusion. The leukapheresis product will undergo TCR alfa beta depletion following the standardized protocol. Receives: Other: Biological: TCR alfa beta T cell depletion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
The probability of overall survival estimated by the Kaplan-Meier method at 1 year after HSCT
Measured: 1 year after HSCT
Secondary outcomes (6)
Transplant Related Mortality (TRM)
transplant-related mortality estimated with cumulative incidence curve, considering relapse as a competitive risk
Measured: 24 months after transplantation
Acute Graft Versus Host Diseases (аGVHD)
incidence of aGVHD II-IV stage estimated with cumulative incidence curve, considering graft rejection and death as competitive risks
Measured: 12 months after transplantation
Chronic Graft Versus Host Diseases (cGVHD)
incidence of cGVHD estimated with cumulative incidence curve, considering graft rejection and death as competitive risks
Measured: 1 year after HSCT
Cellular Immunological Reconstitution
Number of participants, who reached immune recovery - CD19+ lymphocytes subsets
Measured: 2 years after HSCT
Percentage of Patients With Full Donor Chimerism
Percentage of patients with full (more than 90%) donor chimerism among survivals
Measured: last follow-up
Viral Infections After Transplant
number of patients with CMV reactivation (detection of any grade of CMV viremia after HSCT)
Measured: 12 months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2014 (estimated)
- Study startJul 2012
- Primary completionDec 2017
- Study completionJun 2018
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 (1)Papers the sponsor has linked to this study.
- Other trials for Primary Immune Deficiency DisorderStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexei Maschan, Professor, Study chair, Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and ImmunologyDmitry Balashov, MD, PhD, Principal investigator, Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02327351
- Sponsor's protocol ID
- TCRabPID-2012
- Status last verified
- Feb 2021
- First submitted
- 18 Dec 2014
- Last updated
- 26 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Balashov D, Shcherbina A, Maschan M, Trakhtman P, Skvortsova Y, Shelikhova L, Laberko A, Livshits A, Novichkova G, Maschan A. Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRalphabeta and CD19 Depletion in Children with Primary Immunodeficiency Syndromes. Biol Blood Marrow Transplant. 2015 Nov;21(11):1955-62. doi: 10.1016/j.bbmt.2015.07.008. Epub 2015 Jul 15.
PubMed 26187864
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II/III Study of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated and Haploidentical Donors After TCR Alfa Beta Negative Selection in Pediatric Patients With Primary Immunodeficiency Diseases
- ClinicalTrials.gov ID
- NCT02327351
- Acronym / sponsor ID
- TCRabPID-2012
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- Jul 2012 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 30 Dec 2014 (estimated)
- Results
- Posted 26 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Treatment Study to assess of safety and efficiency of T cells receptor (TCR) alfa beta depleted graft for hematopoietic stem cell transplantation (HSCT) from haploidentical and unrelated donors in patients with primary immunodeficiency diseases
Detailed description
Infections, graft versus host diseases (GVHD) and associated morbidity and mortality remains significant problems after unrelated and haploidentical hematopoietic stem sell transplantation (HSCT) in patients with primary immunodeficiency diseases (PID). In this study the hypothesis is that the transplantation of TCR alfa beta depleted peripheral blood stem cells (PBSC) would offers advantages over the use of positively selected CD34+ stem cells in haploidentical HSCT and non-manipulated graft in unrelated HSCT.
The purpose of this study is to evaluate the safety and efficiency of the selective infusion of TCR alfa beta T cell depleted graft in pediatric patients with PID receiving HSCT from haploidentical and unrelated donors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TCR alfa beta depletion | Experimental | Other: Biological: TCR alfa beta T cell depletionTCR alfa beta depleted graft, infusion. The leukapheresis product will undergo TCR alfa beta depletion following the standardized protocol. |
Who may qualify
- Ages
- 1 month to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Patients aged ≥ 1 months and < 19 years
- Patients diagnosed with Primary Immunodeficiency Diseases eligible for an allogeneic transplantation and lacking a related HLA-matched donor
- Lansky/Karnofsky score > 40, WHO > 4
- Signed written informed consent
Key exclusion criteria (5 listed)
- Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 ml / min)
- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction <40%)
- Serious concurrent uncontrolled medical disorder
- Pregnant or breast feeding female patient
- Lack of parents' informed consent.
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 |
|---|---|---|
| Biological: TCR alfa beta T cell depletion | Other | TCR alfa beta depletion |
Primary outcome
Overall Survival
Time frame: 1 year after HSCT
The probability of overall survival estimated by the Kaplan-Meier method at 1 year after HSCT
6 secondary outcomes
Transplant Related Mortality (TRM)
Time frame: 24 months after transplantation
Acute Graft Versus Host Diseases (аGVHD)
Time frame: 12 months after transplantation
Chronic Graft Versus Host Diseases (cGVHD)
Time frame: 1 year after HSCT
Cellular Immunological Reconstitution
Time frame: 2 years after HSCT
Percentage of Patients With Full Donor Chimerism
Time frame: last follow-up
Viral Infections After Transplant
Time frame: 12 months after transplantation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26187864Balashov D, Shcherbina A, Maschan M, Trakhtman P, Skvortsova Y, Shelikhova L, Laberko A, Livshits A, Novichkova G, Maschan A. Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRalphabeta and CD19 Depletion in Children with Primary Immunodeficiency Syndromes. Biol Blood Marrow Transplant. 2015 Nov;21(11):1955-62. doi: 10.1016/j.bbmt.2015.07.008. Epub 2015 Jul 15.
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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.
Alexei Maschan, Professor study chair
Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
Dmitry Balashov, MD, PhD principal investigator
Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Biological: TCR alfa beta T cell depletion in people with Primary Immune Deficiency Disorder and Hematopoietic Stem Cell Transplantation, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
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 4 inclusion and 5 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: finished, as of the sponsor's last update on 26 Feb 2021. 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 Russia. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 26 Feb 2021). 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?
Overall Survival (time frame: 1 year after HSCT). 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 NCT02327351, which also lists 1 linked publication.
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 26 Feb 2021.