Wiskott-Aldrich SyndromePhase 2NCT03019809
A Trial of Plerixafor/G-CSF as Additional Agents for Conditioning Before TCR Alpha/Beta Depleted HSCT in WAS Patients
A Phase 2 study testing G-CSF for Conditioning before HSCT. and Plerixafor for Conditioning before HSCT. in people with Wiskott-Aldrich Syndrome 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 conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after transplantation with TCR alpha/beta grafts depletion in patient with Wiskott-Aldrich syndrome. Read more about this study
- Who is it for?
- Ages 1 month to 19 years
- Conditions the study is for
- Wiskott-Aldrich Syndrome, Hematopoietic Stem Cell Transplantation, Graft Failure
- What is being tested?
- G-CSF for Conditioning before HSCT. and Plerixafor for Conditioning before HSCT.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteRussia
- Study dates
- Jun 2016to Jul 2019
- 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 1 month to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients aged ≥ 1 months and < 19 years
- Patients diagnosed with Wiskott-Aldrich syndrome 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
- Lack of parents' informed consent.
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
Moscow, 117997
Dmitry Balashov, MD, PhD, +7(495)287-6570 ext. 6534, bala8@yandex.ru
Michael Maschan, Professor, +7(926)287-6570, mmaschan@yandex.ru
About this study
Official title: A Trial of Plerixafor With G-CSF as Additional Agents in Conditioning Regimen for Prevention of Graft Failure After Transplantation With TCR Alpha/Beta Grafts Depletion in Patients With Wiskott-Aldrich Syndrome.
Treatment Study to assess of safety and efficiency of conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after transplantation with TCR alpha/beta grafts depletion in patient with Wiskott-Aldrich syndrome.
Read the detailed description
Severe graft dysfunction, such as the degree of donor chimerism predominantly in the myeloid compartment is one of major problem in patients with Wiskott-Aldrich syndrome (WAS), especially after hematopoietic stem cell transplantation (HSCT) from alternative donor. It often leads to the development of severe thrombocytopenia or even transplants rejection. In this study the hypothesis is that the use of plerixafor and G-CSF as additional agents in conditioning regimen would offers advantages due to lowing risk of mixed chimerism after HSCT. This effect is based on the fact that simultaneous use of plerixafor with G-CSF is efficient in inducing stem cell release and opening of bone marrow (BM) niches. Moreover, stem cell release probably leads to liberation of host stem cells from the anti-apoptotic effects of the BM stroma for the more powerful effect of chemotherapy.
In this study, the investigators use TCR alpha/beta grafts depletion of the grafts as basic technology for HSCT from haploidentical and unrelated donors approved in Institution.
Thus, the purpose of this study is to evaluate the safety and efficiency of myeloablative conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after transplantation with TCR alpha/beta grafts depletion in patients with Wiskott-Aldrich syndrome.
- Being tested
- G-CSF for Conditioning before HSCT., Plerixafor for Conditioning before HSCT.
- Medical subject headings
- Wiskott-Aldrich Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G-CSF for Conditioning before HSCT.Biological
Mobilization of hematopoietic stem (HSC) into circulation
Plerixafor for Conditioning before HSCT.Biological
Directed inhibition of CXC chemokine receptor type 4 (CXCR4) for opening enough BM niches for adequate donor HSC engraftment.
| Study group | Role | What they receive |
|---|---|---|
| Plerixafor/G-CSF for HSCT conditioning | Experimental | Myeloablative conditioning regimen with Plerixafor and G-CSF as addition agents before stem cell transplantation in WAS patients. Receives: Biological: G-CSF for Conditioning before HSCT.; Biological: Plerixafor for Conditioning before HSCT. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event free survival (EFS)
The EFS probability compared with historical control. We mean event as patient's death, second transplantation or persistence of severe thrombocytopenia
Measured: 24 months
Secondary outcomes (8)
Overall survival (OS)
The OS probability compared with historical control.
Measured: 24 months
Percentage of patients with full/mixed donor chimerism
Evaluation of the percentage of patients with the full/mixed donor chimerism (whole blood and CD3+ lineage). In addition, patients will be divided in accordance with % of donors cells: >95%; 50%-95%; 10%-49%; <10%. All data will be compared with historical control
Measured: 12 months
Transplant related mortality (TRM)
The TRM probability compared with historical control.
Measured: 24 months
Severe thrombocytopenia (ST)
The ST probability after HSCT compared with historical control
Measured: 24 months
Autoimmune complications (AC)
The AC probability after HSCT compared with historical control
Measured: 24 months
Acute Graft Versus Host Diseases (aGVHD)
Cumulative Incidence and severity of aGVHD
Measured: 12 months
Chronic Graft Versus Host Diseases (cGVHD)
Cumulative Incidence and severity of cGVHD
Measured: 24 months
Plerixafor related complications (PRC)
PRC: severity, features, incidence
Measured: 2 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2017 (estimated)
- Study startJun 2016
- Primary completionDec 2018
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Wiskott-Aldrich SyndromeStudies 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
- 30 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
- Investigators
- Alexei Maschan, Professor, Study chair, Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and ImmunologyDmitry Balashov, Principal investigator, Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03019809
- Sponsor's protocol ID
- WAS_PG 2016
- Status last verified
- Dec 2018
- First submitted
- 11 Jan 2017
- Last updated
- 12 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Balashov D, Laberko A, Shcherbina A, Trakhtman P, Abramov D, Gutovskaya E, Kozlovskaya S, Shelikhova L, Novichkova G, Maschan M, Rumiantsev A, Maschan A. A Conditioning Regimen with Plerixafor Is Safe and Improves the Outcome of TCRalphabeta+ and CD19+ Cell-Depleted Stem Cell Transplantation in Patients with Wiskott-Aldrich Syndrome. Biol Blood Marrow Transplant. 2018 Jul;24(7):1432-1440. doi: 10.1016/j.bbmt.2018.03.006. Epub 2018 Mar 14.
PubMed 29550630
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of Plerixafor With G-CSF as Additional Agents in Conditioning Regimen for Prevention of Graft Failure After Transplantation With TCR Alpha/Beta Grafts Depletion in Patients With Wiskott-Aldrich Syndrome.
- ClinicalTrials.gov ID
- NCT03019809
- Acronym / sponsor ID
- WAS_PG 2016
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- Jun 2016 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Jul 2019 (estimated)
- First posted
- 13 Jan 2017 (estimated)
- 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.
Treatment Study to assess of safety and efficiency of conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after transplantation with TCR alpha/beta grafts depletion in patient with Wiskott-Aldrich syndrome.
Detailed description
Severe graft dysfunction, such as the degree of donor chimerism predominantly in the myeloid compartment is one of major problem in patients with Wiskott-Aldrich syndrome (WAS), especially after hematopoietic stem cell transplantation (HSCT) from alternative donor. It often leads to the development of severe thrombocytopenia or even transplants rejection. In this study the hypothesis is that the use of plerixafor and G-CSF as additional agents in conditioning regimen would offers advantages due to lowing risk of mixed chimerism after HSCT. This effect is based on the fact that simultaneous use of plerixafor with G-CSF is efficient in inducing stem cell release and opening of bone marrow (BM) niches. Moreover, stem cell release probably leads to liberation of host stem cells from the anti-apoptotic effects of the BM stroma for the more powerful effect of chemotherapy.
In this study, the investigators use TCR alpha/beta grafts depletion of the grafts as basic technology for HSCT from haploidentical and unrelated donors approved in Institution.
Thus, the purpose of this study is to evaluate the safety and efficiency of myeloablative conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after transplantation with TCR alpha/beta grafts depletion in patients with Wiskott-Aldrich syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Plerixafor/G-CSF for HSCT conditioning | Experimental | Biological: G-CSF for Conditioning before HSCT., Biological: Plerixafor for Conditioning before HSCT.Myeloablative conditioning regimen with Plerixafor and G-CSF as addition agents before stem cell transplantation in WAS patients. |
Who may qualify
- Ages
- 1 month to 19 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 Wiskott-Aldrich syndrome 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 (4 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
- 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 |
|---|---|---|
| G-CSF for Conditioning before HSCT.Mobilization of hematopoietic stem (HSC) into circulation | Biological | Plerixafor/G-CSF for HSCT conditioning |
| Plerixafor for Conditioning before HSCT.Directed inhibition of CXC chemokine receptor type 4 (CXCR4) for opening enough BM niches for adequate donor HSC engraftment. | Biological | Plerixafor/G-CSF for HSCT conditioning |
Primary outcome
Event free survival (EFS)
Time frame: 24 months
The EFS probability compared with historical control. We mean event as patient's death, second transplantation or persistence of severe thrombocytopenia
8 secondary outcomes
Overall survival (OS)
Time frame: 24 months
Percentage of patients with full/mixed donor chimerism
Time frame: 12 months
Transplant related mortality (TRM)
Time frame: 24 months
Severe thrombocytopenia (ST)
Time frame: 24 months
Autoimmune complications (AC)
Time frame: 24 months
Acute Graft Versus Host Diseases (aGVHD)
Time frame: 12 months
Chronic Graft Versus Host Diseases (cGVHD)
Time frame: 24 months
Plerixafor related complications (PRC)
Time frame: 2 week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2018.
- Derived from this study: PubMed 29550630Balashov D, Laberko A, Shcherbina A, Trakhtman P, Abramov D, Gutovskaya E, Kozlovskaya S, Shelikhova L, Novichkova G, Maschan M, Rumiantsev A, Maschan A. A Conditioning Regimen with Plerixafor Is Safe and Improves the Outcome of TCRalphabeta+ and CD19+ Cell-Depleted Stem Cell Transplantation in Patients with Wiskott-Aldrich Syndrome. Biol Blood Marrow Transplant. 2018 Jul;24(7):1432-1440. doi: 10.1016/j.bbmt.2018.03.006. Epub 2018 Mar 14.
Related trials for Wiskott-Aldrich Syndrome
Active, not recruiting
Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
SCID, Omenn's Syndrome
Enrolling by invitationObservational study
Analysis of the Therapeutic and Clinical Profile of Cannabinoid Treatments: A Real-World Study
Chronic Pain, Depression Disorders
RecruitingObservational study
Data Collection Study of Patients With Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT With RIC
Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes
Enrolling by invitationPhase 1/2
Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
Severe Combined Immunodeficiency (SCID), Immunodeficiency With Predominant T-cell Defect, Unspecified
RecruitingPhase 2
Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT
Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes
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 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 study testing G-CSF for Conditioning before HSCT. and Plerixafor for Conditioning before HSCT. in people with Wiskott-Aldrich Syndrome 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 4 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 12 Dec 2018. 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 (+7(495)287-6570 ext. 6534, bala8@yandex.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event free survival (EFS) (time frame: 24 months). 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 NCT03019809, 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 12 Dec 2018.