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A Trial of Plerixafor/G-CSF as Additional Agents for Conditioning Before TCR Alpha/Beta Depleted HSCT in WAS Patients

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ClinicalTrials.gov Identifier: NCT03019809
Recruitment Status : Recruiting
First Posted : January 13, 2017
Last Update Posted : December 12, 2018
Sponsor:
Information provided by (Responsible Party):
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Brief 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.

Condition or disease Intervention/treatment Phase
Wiskott-Aldrich Syndrome Hematopoietic Stem Cell Transplantation Graft Failure Biological: G-CSF for Conditioning before HSCT. Biological: Plerixafor for Conditioning before HSCT. Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : June 2016
Actual Primary Completion Date : December 2018
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Plerixafor

Arm Intervention/treatment
Experimental: Plerixafor/G-CSF for HSCT conditioning
Myeloablative conditioning regimen with Plerixafor and G-CSF as addition agents before stem cell transplantation in WAS patients.
Biological: G-CSF for Conditioning before HSCT.
Mobilization of hematopoietic stem (HSC) into circulation

Biological: Plerixafor for Conditioning before HSCT.
Directed inhibition of CXC chemokine receptor type 4 (CXCR4) for opening enough BM niches for adequate donor HSC engraftment.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 24 months ]
    The OS probability compared with historical control.

  2. Percentage of patients with full/mixed donor chimerism [ Time Frame: 12 months ]
    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

  3. Transplant related mortality (TRM) [ Time Frame: 24 months ]
    The TRM probability compared with historical control.

  4. Severe thrombocytopenia (ST) [ Time Frame: 24 months ]
    The ST probability after HSCT compared with historical control

  5. Autoimmune complications (AC) [ Time Frame: 24 months ]
    The AC probability after HSCT compared with historical control

  6. Acute Graft Versus Host Diseases (aGVHD) [ Time Frame: 12 months ]
    Cumulative Incidence and severity of aGVHD

  7. Chronic Graft Versus Host Diseases (cGVHD) [ Time Frame: 24 months ]
    Cumulative Incidence and severity of cGVHD

  8. Plerixafor related complications (PRC) [ Time Frame: 2 week ]
    PRC: severity, features, incidence



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03019809


Contacts
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Contact: Dmitry Balashov, MD, PhD +7(495)287-6570 ext 6534 bala8@yandex.ru
Contact: Michael Maschan, Professor +7(926)651-2145 mmaschan@yandex.ru

Locations
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Russian Federation
Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology Recruiting
Moscow, Russian Federation, 117997
Contact: Dmitry Balashov, MD, PhD    +7(495)287-6570 ext 6534    bala8@yandex.ru   
Contact: Michael Maschan, Professor    +7(926)287-6570    mmaschan@yandex.ru   
Sub-Investigator: Michael Maschan, Professor         
Sub-Investigator: Alexandra Laberko, MD         
Sub-Investigator: Svetlana Kozlovskaya, MD         
Sub-Investigator: Elena Gutovskaya, MD         
Sub-Investigator: Anna Shcherbina, Professor         
Sponsors and Collaborators
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Investigators
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Study Chair: Alexei Maschan, Professor Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
Principal Investigator: Dmitry Balashov Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
ClinicalTrials.gov Identifier: NCT03019809     History of Changes
Other Study ID Numbers: WAS_PG 2016
First Posted: January 13, 2017    Key Record Dates
Last Update Posted: December 12, 2018
Last Verified: December 2018

Additional relevant MeSH terms:
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Syndrome
Wiskott-Aldrich Syndrome
Disease
Pathologic Processes
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphopenia
Leukopenia
Leukocyte Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Immunologic Deficiency Syndromes
Immune System Diseases
Lenograstim
Plerixafor octahydrochloride
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents