Plerixafor/G-CSF as Additional Agents for Conditioning Before HSCT in CGD Patients

A Clinical Trial of Plerixafor With G-CSF as Additional Agents in Conditioning Regimen for Prevention of Graft Failure in Patients With Chronic Granulomatous Disease

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 in patients with chronic granulomatous disease

Study Overview

• Status: Unknown
• Conditions: Chronic Granulomatous Disease
• Intervention / Treatment: Drug: Plerixafor; Drug: Gcsf

Detailed Description

Severe primary or secondary graft dysfunction is one of major problem in patients with Chronic granulomatous disease (CGD). In this study the hypothesis is that the use of plerixafor and G-CSF as additional agents in conditioning regimen would offers advantages. The effect is based on mobilizing bone marrow stem cells into the peripheral blood and blocking CXCR4 chemokine receptors to prevent stem cell homing. Thus, some have hypothesized that plerixafor and G-CSF make free stromal space of the bone marrow available for donor stem cell engraftment. 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. 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 stem cell transplantation in patients with chronic granulomatous disease.

• Study Type: Interventional
• Enrollment (Anticipated): 17
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dmitry Balashov, MD; Phone Number: +79265791817; Email: bala8@yandex.ru
• Study Contact Backup: Name: Svetlana Kozlovskaya, MD; Phone Number: +79165587891; Email: lana.n.kozlovskaya@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 117997
    • Recruiting
    • Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
    • Principal Investigator: Dmitry Balashov, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 24 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients aged ≥ 1 months and < 25 years Patients diagnosed with CGD eligible for an allogeneic transplantation Signed written informed consent

Exclusion Criteria:

Lack of informed consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plerixafor/G-CSF; Plerixafor/G-CSF for HSCT conditioning Myeloablative conditioning regimen with Plerixafor as addition agent before stem cell transplantation in CGD patients	Drug: Plerixafor; Plerixafor for Conditioning before HSCT.; Drug: Gcsf; GCSF for Conditioning before HSCT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival	The EFS probability compared with historical control. We mean event as primary (non-engraftment) and secondary (rejection) graft dysfunction.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Overall survival	The OS probability compared with historical control	1 year
Proportion 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	30 days
3. Transplant related mortality	The TRM probability compared with historical control.	1 year
4. Acute Graft Versus Host Diseases	Cumulative Incidence of aGVHD	100 days
5. Incidence of Plerixafor related toxicity	severity, features, incidence	100 days

Collaborators and Investigators

• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2019
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): September 17, 2019
• Last Update Submitted That Met QC Criteria: September 16, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: stem cell transplantation; plerixafor; graft failure; conditioning regimen; chronic granulomatous disease
• Additional Relevant MeSH Terms: Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Leukocyte Disorders; Phagocyte Bactericidal Dysfunction; Granuloma; Granulomatous Disease, Chronic; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Plerixafor
• Other Study ID Numbers: NCPHOI-2018-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No