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

December 10, 2018 updated by: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 117997
        • Recruiting
        • Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
        • Contact:
          • Dmitry Balashov, MD, PhD
          • Phone Number: 6534 +7(495)287-6570
          • Email: bala8@yandex.ru
        • Contact:
        • 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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 19 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 24 months
The OS probability compared with historical control.
24 months
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
12 months
Transplant related mortality (TRM)
Time Frame: 24 months
The TRM probability compared with historical control.
24 months
Severe thrombocytopenia (ST)
Time Frame: 24 months
The ST probability after HSCT compared with historical control
24 months
Autoimmune complications (AC)
Time Frame: 24 months
The AC probability after HSCT compared with historical control
24 months
Acute Graft Versus Host Diseases (aGVHD)
Time Frame: 12 months
Cumulative Incidence and severity of aGVHD
12 months
Chronic Graft Versus Host Diseases (cGVHD)
Time Frame: 24 months
Cumulative Incidence and severity of cGVHD
24 months
Plerixafor related complications (PRC)
Time Frame: 2 week
PRC: severity, features, incidence
2 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Investigators

  • 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 and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2016

Primary Completion (Actual)

December 1, 2018

Study Completion (Anticipated)

July 1, 2019

Study Registration Dates

First Submitted

January 11, 2017

First Submitted That Met QC Criteria

January 12, 2017

First Posted (Estimate)

January 13, 2017

Study Record Updates

Last Update Posted (Actual)

December 12, 2018

Last Update Submitted That Met QC Criteria

December 10, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WAS_PG 2016

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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