Severe Congenital NeutropeniaPhase 2NCT04844177
Total Lymphoid Irradiation Pre-HSCT in Severe Congenital Neutropenia
A Phase 2 study testing conditioning with TLI in people with Severe Congenital Neutropenia and GATA2 Deficiency, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
Trial summary
Severe congenital neutropenia (SCN) is a group of primary immunodeficiencies caused by distinct gene mutations and characterized by neutrophil maturation impairment, which leads to neutropenia, predisposition to severe bacterial and fungal infections, and myeloid malignancies. Read more about this study
- Who is it for?
- Ages 18 months to 21 years
- Conditions the study is for
- Severe Congenital Neutropenia, GATA2 Deficiency
- What is being tested?
- conditioning with TLI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteRussia
- Study dates
- 14 Apr 2021to Apr 2026
- Phase
- Phase 2
- 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 18 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Clinical indications for HSCT in SCN: clinical diagnosis of SCN with (1) no adequate response to G-CST therapy or (2) with malignant transformation or (3) unfavorable mutations of known SCN genes
- GATA2 deficiency
- SCN patients age at HSCT 18 months - 21 years
- GATA2 deficiency patients age at HSCT more than 10 years
- Signed informed consent to participate in the study
- Presence of HLA-matched unrelated or HLA-mismatched related donor
Who cannot join
- Presence of HLA matched related donor in absence of pathologic SCN gene mutation
- Inability to perform TCRab/CD19 graft depletion
- Contraindications for HSCT due to patients somatic condition
Trial locations and contacts
1 site in 1 country.
Alexandra Laberko, MD contact
Russia1 site
HSCT department
Moscow, 117198
Dmitry Balashov, MD, PhD, 84956647078, Dmitriy.Balashov@fccho-moscow.ru
About this study
Official title: Pilot Prospective Clinical Study of Safety and Efficacy of Conditioning Regimen With Total Lymphoid Irradiation Before Allogeneic Hematopoietic Stem Cell Transplantation With TCRab/CD19 Graft Depletion in Severe Congenital Neutropenia
Severe congenital neutropenia (SCN) is a group of primary immunodeficiencies caused by distinct gene mutations and characterized by neutrophil maturation impairment, which leads to neutropenia, predisposition to severe bacterial and fungal infections, and myeloid malignancies. Granulocyte-colony stimulation factor is used for pathogenetic therapy, however, no adequate response is seen in some patients.
The only curative option for SCN is hematopoietic stem cell transplantation (HSCT). An indication for HSCT in SCN is: no adequate response to G-CSF therapy, or development of malignancies, or found unfavorable mutations of SCN genes, leading to poor response to G-CSF and high risk of malignant transformation.
Read more
One of the major peculiarities of HSCT in SCN is a high risk of graft failure. That was described in few studies in SCN transplantation and was also observed in our SCN HSCT cohort. We also consider the role of TCRab/CD19 graft depletion, which is routinely used in our center for GVHD prophylaxis in increased risks of graft failure.
Another problem often observed in our patients is the relatively high risks of death of infections, developed after graft failure.
Due to predominantly early HSCT graft failure development, non-sufficient immuablation is presumed as the main reason for graft failure. Because of the low level of toxicity, associated with TCRab/CD19 depletion usage, this strategy is planned to be used in the current study. To increase an immunoablative potential of conditioning regimen in SCN, total lymphoid irradiation will be studied in combination with myeloablative agents and standardly used serotherapy.
- Conditions
- Severe Congenital Neutropenia, GATA2 Deficiency
- Being tested
- conditioning with TLI
- Medical subject headings
- Neutropenia, Severe Congenital, Autosomal Recessive 3, GATA2 Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
conditioning with TLIOther
Total lymphoid irradiation 4 Gy (days -7, -6) in combination with:
- Fludarabine 150 mg/m2 (days-6, -5, -4, -3, -2)
- Cyclophosphamide 120 mg/kg (days -5, -4, -3)
- Thymoglogulin (Genzyme) 5 mg/kg (days -5, -4)
- Melphalan 180 mg/m2 (day -2)
- Rituximab 100 mg/m2 (day -1)
- Hematopoietic stem cell graft infusion after TCRab/CD19 depletion - day 0
| Study group | Role | What they receive |
|---|---|---|
| intervention/treatment | Experimental | Total lymphoid irradiation 4 Gy (days -7, -6) in combination with:
* Fludarabine 150 mg/m2 (days-6, -5, -4, -3, -2)
* Cyclophosphamide 120 mg/kg (days -5, -4, -3)
* Thymoglogulin (Genzyme) 5 mg/kg (days -5, -4)
* Melphalan 180 mg/m2 (day -2)
* Rituximab 100 mg/m2 (day -1)
* Hematopoietic stem cell graft infusion after TCRab/CD19 depletion - day 0 Receives: Other: conditioning with TLI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Measured: 2 years post HSCT
event free survival
events - death, graft failure, secondary malignancy, relapse of malignancy
Measured: 2 years post HSCT
Secondary outcomes (8)
Cumulative incidence of transplant related mortality
Measured: 2 years post HSCT
Cumulative incidence of graft failure
non-engraftment, secondary graft rejection, severe non-reversible bone marrow failure
Measured: 2 years post HSCT
Cumulative incidence of graft versus host disease
Measured: 2 years post HSCT
number of patients with donor chimerism
Measured: 2 years post HSCT
Incidence of secondary malignancies
number of patients
Measured: 2 years post HSCT
Cumulative incidence of engraftment
Measured: 100 days post HSCT
Incidence of early severe organ toxicity
number of patients
Measured: 100 days post HSCT
cumulative incidence of infectious complications
infectious complication - CMV, EVB, ADV reactivation
Measured: 1 year after HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2021
- Study start14 Apr 2021 (estimated)
- Primary completionApr 2024 (estimated)
- Study completionApr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Congenital NeutropeniaStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04844177
- Sponsor's protocol ID
- NCPHOI-2021-02
- Status last verified
- Apr 2021
- First submitted
- 9 Apr 2021
- Last updated
- 14 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Prospective Clinical Study of Safety and Efficacy of Conditioning Regimen With Total Lymphoid Irradiation Before Allogeneic Hematopoietic Stem Cell Transplantation With TCRab/CD19 Graft Depletion in Severe Congenital Neutropenia
- ClinicalTrials.gov ID
- NCT04844177
- Acronym / sponsor ID
- NCPHOI-2021-02
- Conditions
- Severe Congenital Neutropenia, GATA2 Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- 14 Apr 2021 (estimated)
- Primary completion
- Apr 2024 (estimated)
- Study completion
- Apr 2026 (estimated)
- First posted
- 14 Apr 2021 (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.
Severe congenital neutropenia (SCN) is a group of primary immunodeficiencies caused by distinct gene mutations and characterized by neutrophil maturation impairment, which leads to neutropenia, predisposition to severe bacterial and fungal infections, and myeloid malignancies. Granulocyte-colony stimulation factor is used for pathogenetic therapy, however, no adequate response is seen in some patients.
The only curative option for SCN is hematopoietic stem cell transplantation (HSCT). An indication for HSCT in SCN is: no adequate response to G-CSF therapy, or development of malignancies, or found unfavorable mutations of SCN genes, leading to poor response to G-CSF and high risk of malignant transformation.
One of the major peculiarities of HSCT in SCN is a high risk of graft failure. That was described in few studies in SCN transplantation and was also observed in our SCN HSCT cohort. We also consider the role of TCRab/CD19 graft depletion, which is routinely used in our center for GVHD prophylaxis in increased risks of graft failure.
Another problem often observed in our patients is the relatively high risks of death of infections, developed after graft failure.
Due to predominantly early HSCT graft failure development, non-sufficient immuablation is presumed as the main reason for graft failure. Because of the low level of toxicity, associated with TCRab/CD19 depletion usage, this strategy is planned to be used in the current study. To increase an immunoablative potential of conditioning regimen in SCN, total lymphoid irradiation will be studied in combination with myeloablative agents and standardly used serotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intervention/treatment | Experimental | Other: conditioning with TLITotal lymphoid irradiation 4 Gy (days -7, -6) in combination with: * Fludarabine 150 mg/m2 (days-6, -5, -4, -3, -2) * Cyclophosphamide 120 mg/kg (days -5, -4, -3) * Thymoglogulin (Genzyme) 5 mg/kg (days -5, -4) * Melphalan 180 mg/m2 (day -2) * Rituximab 100 mg/m2 (day -1) * Hematopoietic stem cell graft infusion after TCRab/CD19 depletion - day 0 |
Who may qualify
- Ages
- 18 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Clinical indications for HSCT in SCN: clinical diagnosis of SCN with (1) no adequate response to G-CST therapy or (2) with malignant transformation or (3) unfavorable mutations of known SCN genes
- GATA2 deficiency
- SCN patients age at HSCT 18 months - 21 years
- GATA2 deficiency patients age at HSCT more than 10 years
- Signed informed consent to participate in the study
Key exclusion criteria (3 listed)
- Presence of HLA matched related donor in absence of pathologic SCN gene mutation
- Inability to perform TCRab/CD19 graft depletion
- Contraindications for HSCT due to patients somatic condition
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 |
|---|---|---|
| conditioning with TLITotal lymphoid irradiation 4 Gy (days -7, -6) in combination with: * Fludarabine 150 mg/m2 (days-6, -5, -4, -3, -2) * Cyclophosphamide 120 mg/kg (days -5, -4, -3) * Thymoglogulin (Genzyme) 5 mg/kg (days -5, -4) * Melphalan 180 mg/m2 (day -2) * Rituximab 100 mg/m2 (day -1) * Hematopoietic stem cell graft infusion after TCRab/CD19 depletion - day 0 | Other | intervention/treatment |
Primary outcome
Overall survival
Time frame: 2 years post HSCT
event free survival
Time frame: 2 years post HSCT
events - death, graft failure, secondary malignancy, relapse of malignancy
8 secondary outcomes
Cumulative incidence of transplant related mortality
Time frame: 2 years post HSCT
Cumulative incidence of graft failure
Time frame: 2 years post HSCT
Cumulative incidence of graft versus host disease
Time frame: 2 years post HSCT
number of patients with donor chimerism
Time frame: 2 years post HSCT
Incidence of secondary malignancies
Time frame: 2 years post HSCT
Cumulative incidence of engraftment
Time frame: 100 days post HSCT
Incidence of early severe organ toxicity
Time frame: 100 days post HSCT
cumulative incidence of infectious complications
Time frame: 1 year after HSCT
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2021.
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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.
Alexandra Laberko, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing conditioning with TLI in people with Severe Congenital Neutropenia and GATA2 Deficiency, 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 6 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 14 Apr 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dmitry Balashov, MD, PhD (84956647078, Dmitriy.Balashov@fccho-moscow.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: 2 years post HSCT). 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?
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 14 Apr 2021.