Efficacy and Safety of Cytotect®CP, Hyperimmune Anti-CMV IVIg as CMV Prophylaxis in Patients Developing Acute Grade II-IV GVHD After Allogeneic Hematopoietic Cell Transplantation. (CMV-GVHD)
Primary Purpose
Cytomegalovirus Infections
Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Cytotect®CP
Sponsored by
About this trial
This is an interventional treatment trial for Cytomegalovirus Infections
Eligibility Criteria
Inclusion Criteria:
- Able to provide informed consent
- Patients before day from 29 days to 150 days of first allo-HCT
- Any indication, any stem cell source, any conditioning, any donor type or HLA-matching
- Patients with positive CMV-serostatus before transplant
- Patients with first episode of grade II-IV acute GVHD requiring systemic corticosteroids ≥1 mg/kg/day
- Absence of CMV infection at the time of inclusion
- Absence of other viral infections (EBV, adenovirus, BK virus) at the time of inclusion
- Absence of dialysis
- Absence of thrombotic microangiopathy
- Absence of macrophage activation syndrome
Exclusion Criteria:
- - Patients receiving corticosteroids > 0.5 mg/kg/day for more than 5 days before inclusion
- Uncontrolled CMV infection within 02 weeks before inclusion
- Inability to understand the investigational nature of the study or to give informed consent
- ECOG Performance Status ≥ 3
- Evidence of relapse of underlying disease
- Patients receiving or having received anti-CMV treatment within 30 days before inclusion (acyclovir and valacyclovir are not considered as CMV prophylaxis)
- Hypersensitivity to Cytotect®CP or to any of the excipients
- Hypersensitivity to human immunoglobulins, especially in patients with antibodies against IgA
- Patients with any contra-indication to Cytotect®CP
- Females either pregnant/breast-feeding or planning to become pregnant
- Patients developing post-DLI grade II-IV acute GVHD
- Freedom privacy
- Absence of medical insurance cover
Sites / Locations
- Hop Claude Huriez Chu LilleRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental group
Arm Description
Outcomes
Primary Outcome Measures
Rate of CMV infection within 16 weeks of Cytotect®CP therapy.
Secondary Outcome Measures
Time from inclusion to death from any cause or death without relapse of the underlying disease within 6 months
Time from inclusion to EBV, adenovirus or BK virus co-infection ≤ 16 weeks.
Time from inclusion to CMV infection ≤ 16 weeks.
Time from inclusion to CMV disease ≤ 16 weeks
Frequency of adverse events (grades 3 and 4)
Analysis of immune reconstitution under Cytotect®CP.
Full Information
NCT ID
NCT05370976
First Posted
May 19, 2021
Last Updated
November 8, 2022
Sponsor
University Hospital, Lille
Collaborators
Biotest
1. Study Identification
Unique Protocol Identification Number
NCT05370976
Brief Title
Efficacy and Safety of Cytotect®CP, Hyperimmune Anti-CMV IVIg as CMV Prophylaxis in Patients Developing Acute Grade II-IV GVHD After Allogeneic Hematopoietic Cell Transplantation.
Acronym
CMV-GVHD
Official Title
Efficacy and Safety of Cytotect®CP, Hyperimmune Anti-CMV IVIg as CMV Prophylaxis in Patients Developing Acute Grade II-IV GVHD After Allogeneic Hematopoietic Cell Transplantation: A Prospective, Open-label, Phase II Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 13, 2022 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Lille
Collaborators
Biotest
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Many risk factors are known to be associated with high risk of developing CMV infection in positive CMV-serostatus patients: negative CMV-serostatus donor, unrelated or mismatched donor, use of antithymocyte globulin (ATG), and development of GVHD. Acute GVHD occurs during the first hundred days after transplantation. In spite of systematic GVHD prophylactic using immunosuppressive agents, approximately 50% of transplantation recipients develop GVHD. The first-line treatment of acute GVHD is methylprednisolone 2 mg/kg/day. Probably because of the use corticosteroids but also due to the GVHD itself, approximately 46% of CMV seropositive patients develop CMV infection (report from the national database of the SFGM-TC, data unpublished yet).
CMV infection leads to longer duration of hospitalization and increases the risk of mortality, particularly in cases of CMV disease. Available antiviral agents used to prevent CMV infections are generally reputed to cause significant side effects. These agents can prevent full immunological post-transplant reconstitution and cause profound cytopenia. Some agents may be responsible for renal impairment, which prevents continuation of immunosuppressive treatment; this is especially the case with calcineurin inhibitors in allo-HCT patients. Indeed, compared to placebo, intravenous ganciclovir has been shown to reduce the risk of CMV infection and disease, although it did not appear to improve overall survival. However, it was responsible for 30% of cases of severe neutropenia in allo-HCT patients, increasing the risk of bacterial and fungal coinfections. CMV infection treatment is commonly based on ganciclovir and foscavir and, to a lesser extent, on other drugs, including cidofovir. However, these drugs cause high levels of toxicity, resulting in myelotoxicity in the case of ganciclovir, or, in the case of foscavir and cidofovir, potential renal failure, incurring treatment discontinuation.
CMV prophylaxis using drugs with fewer side-effects is necessary in patients at high risk of CMV infection.
With its safety profile, Cytotect®CP offers an alternative option for CMV prophylaxis with avoidance of renal and bone marrow impairment.
Considering the high risk of developing CMV infection, we decided to investigate the efficacy and safety of Cytotect®CP in patients requiring systematic corticosteroids (≥ 1 mg/kg/day) for an initial episode of grade II-IV acute GVHD following a first allo-HCT.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental group
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cytotect®CP
Intervention Description
Cytotect®CP in two phases:
Induction phase: 1 ml/kg/week for 4 weeks Maintenance phase: 1 ml/kg/2 weeks for 12 weeks or corticosteroid dose < 0.5 mg/kg, according to which condition occurs first.
Patients developing CMV infection under Cytotect®CP must be given standard anti-CMV treatment (Gancyclovir or Foscarnet) according to their center procedure. Cytotect®CP will be maintained
Primary Outcome Measure Information:
Title
Rate of CMV infection within 16 weeks of Cytotect®CP therapy.
Time Frame
within 16 weeks
Secondary Outcome Measure Information:
Title
Time from inclusion to death from any cause or death without relapse of the underlying disease within 6 months
Time Frame
from inclusion to 16 weeks
Title
Time from inclusion to EBV, adenovirus or BK virus co-infection ≤ 16 weeks.
Time Frame
within the 16 weeks from inclusion
Title
Time from inclusion to CMV infection ≤ 16 weeks.
Time Frame
within the 16 weeks from inclusion
Title
Time from inclusion to CMV disease ≤ 16 weeks
Time Frame
within the 16 weeks from inclusion
Title
Frequency of adverse events (grades 3 and 4)
Time Frame
from 1st administration of Cytotect®CP throughout the 4 weeks after the last administration of Cytotect®CP, an average 20 weeks
Title
Analysis of immune reconstitution under Cytotect®CP.
Time Frame
Througth study completion, an average 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Able to provide informed consent
Patients before day from 29 days to 150 days of first allo-HCT
Any indication, any stem cell source, any conditioning, any donor type or HLA-matching
Patients with positive CMV-serostatus before transplant
Patients with first episode of grade II-IV acute GVHD requiring systemic corticosteroids ≥1 mg/kg/day
Absence of CMV infection at the time of inclusion
Absence of other viral infections (EBV, adenovirus, BK virus) at the time of inclusion
Absence of dialysis
Absence of thrombotic microangiopathy
Absence of macrophage activation syndrome
Exclusion Criteria:
- Patients receiving corticosteroids > 0.5 mg/kg/day for more than 5 days before inclusion
Uncontrolled CMV infection within 02 weeks before inclusion
Inability to understand the investigational nature of the study or to give informed consent
ECOG Performance Status ≥ 3
Evidence of relapse of underlying disease
Patients receiving or having received anti-CMV treatment within 30 days before inclusion (acyclovir and valacyclovir are not considered as CMV prophylaxis)
Hypersensitivity to Cytotect®CP or to any of the excipients
Hypersensitivity to human immunoglobulins, especially in patients with antibodies against IgA
Patients with any contra-indication to Cytotect®CP
Females either pregnant/breast-feeding or planning to become pregnant
Patients developing post-DLI grade II-IV acute GVHD
Freedom privacy
Absence of medical insurance cover
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ibrahim Yakoub-Agha, MD,PhD
Phone
0320445962
Ext
+33
Email
ibrahim.yakoubagha@chru-lille.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ibrahim Yakoub-Agha, MD,PhD
Organizational Affiliation
University Hospital, Lille
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hop Claude Huriez Chu Lille
City
Lille
Country
France
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Cytotect®CP, Hyperimmune Anti-CMV IVIg as CMV Prophylaxis in Patients Developing Acute Grade II-IV GVHD After Allogeneic Hematopoietic Cell Transplantation.
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