Clinical trial NCT03343600: Imatinib for Cytomegalovirus Prophylaxis and Treatment After Allogeneic Hematopoietic Stem Cell Transplantation
Official title: A Randomization, Double Blind, Multicenter Phase II Clinical Trial to Evaluate the Imatinib for Prophylaxis of CMV Infection After Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Patients Who Have Received Allo-HSCT
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: Far Eastern Memorial Hospital
name: Tri-Service General Hospital
name: National Cheng-Kung University Hospital
name: Hualien Tzu Chi General Hospital
First posted: 2017-11-17
Enrollment: 5
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study aim at examining whether blocking platelet-derived growth factor receptor-α by imatinib lowers the risk of post-allogeneic hematopoietic stem cell transplantation CMV infection.

Detailed description: This is a randomized, double-blind, multicenter phase II clinical trial. In the trial, post-allo-HSCT patients with signs of bone marrow engraftment and without evidence of CMV reactivation will be enrolled. All enrolled patients will be monitored for their blood CMV DNA copy numbers by Q-PCR and safety throughout the trial. In addition to their routine post-allo-HSCT care, eligible patients will receive imatinib (100mg/tablet, 2 tablets daily) or placebo (2 tablets daily) administration after myeloid engraftment (defined as absolute neutrophil count higher than 500 for three consecutive days). While receiving the trial therapy, patients will have a regular CMV surveillance every week by the quantification of plasma CMV DNA copies. During the administration of the investigational drugs, other concomitant anti-CMV prophylaxis treatments are prohibited. When a patient has any signs suggesting CMV infection that the treating physician determines that an anti-CMV therapy is indicated, the patient will be defined as failure of prophylaxis for the efficacy evaluation. Whether the conventional anti-CMV therapy is started or not, the investigational drugs with imatinib or placebo will be continued till at least Day+100 unless the patient is defined as prophylaxis failure or withdraws from the study including personal reasons, early mortality, disease recurrence after transplantation, pregnancy, or the investigator decides that the subject should be withdrawn for safety reasons or physical conditions.

Eligibility criteria: Inclusion Criteria:

* Adult patients (Age ≧ 20) who received the first allo-HSCT are eligible;
* Patients with underlying disease of acute leukemia in morphological remission, or myelodysplastic syndrome;
* Received allo-HSCT with HLA-matched sibling or unrelated donors (at least 8/8 match for HLA-A/B/C/DR);
* Evidence of post-transplantation neutrophil engraftment: absolute neutrophil count \> 500/mm3 for at least 3 consecutive days;
* No detectable CMV infection before study enrollment: negative plasma CMV DNA surveillance within passing 2 weeks;
* No previous post-transplantation anti-CMV therapy and no planned prophylactic anti-CMV therapy;
* The patients has the ability to swallow tablets

Exclusion Criteria:

* They have renal insufficiency: serum creatinine \> 2.5 mg/dL;
* They have hepatic dysfunction: serum alanine or aspartate aminotransferase levels of \> 5 times the upper limit of the normal range or a serum total bilirubin of \> 3 mg/dL;
* Patients with history of HIV infection;
* Unstable post-BMT condition or other medical condition deemed not appropriate to be included to this study as judged by investigator;
* Life expectancy less than 3 months;
* Unwillingness or unable to give consent;
* Patients with diseases that are positive for t(9;22) or BCR-ABL fusion gene.

Primary outcomes:
measure: Number of participants free from initiating conventional anti-CMV treatment by Day+100 after allo-HSCT.
timeFrame: From first dosing to 100 days after allo-HSCT (Day+100)
Secondary outcomes:
measure: Number of treatment-related adverse events (AE) by Day+100 after allo-HSCT.
timeFrame: From first dosing to 100 days after allo-HSCT (Day+100)
measure: Time to onset of CMV reactivation defined by peripheral blood CMV copies by Day+100 after allo-HSCT.
timeFrame: From first dosing to 100 days after allo-HSCT (Day+100)
measure: Time to onset of CMV disease diagnosed by investigator by Day+100 after allo-HSCT.
timeFrame: From first dosing to 100 days after allo-HSCT (Day+100)
measure: Number of participants who had progressive hematological disease within 6 months after allo-HSCT.
timeFrame: 6 months post-transplant
measure: Number of participants who died within 6 months after allo-HSCT.
timeFrame: 6 months post-transplant
Other outcomes:
Locations:
city: Hualien City
country: Taiwan
facility: Tzu Chi General Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Chien-Ting Lin, MD
role: PRINCIPAL_INVESTIGATOR
References: