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

Hematopoietic Stem Cell Transplantation Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03019809
• Other study ID #: WAS_PG 2016
• Status: Recruiting
• Phase: Phase 2
• Start date: June 2016
• Est. completion date: July 2019

Study information

• Verified date: December 2018
• Source: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Contact: Dmitry Balashov, MD, PhD
• Phone: +7(495)287-6570
• Email: bala8[@]yandex.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 19 Years

Eligibility

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.

Related Conditions & MeSH terms

• Graft Failure
• Hematopoietic Stem Cell Transplantation
• Syndrome
• Wiskott-Aldrich Syndrome

Intervention

Biological:
• G-CSF for Conditioning before HSCT.
Mobilization of hematopoietic stem (HSC) into circulation
• Plerixafor for Conditioning before HSCT.
Directed inhibition of CXC chemokine receptor type 4 (CXCR4) for opening enough BM niches for adequate donor HSC engraftment.

Locations

Country	Name	City	State
Russian Federation	Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Country where clinical trial is conducted

Russian Federation, 

Outcome

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