Clinical trial NCT01252017: Nilotinib for Cytomegalovirus Prophylaxis and Treatment After Allogeneic Hematopoietic Stem Cell Transplantation
Official title: Cytomegalovirus (CMV) Reactivation in Post-allogeneic Hematopoietic Stem Cell Transplantation(Allo-HSCT) Patients: Salvage and Prophylactic Treatments of Nilotinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Patients Who Have Received Allo-HSCT
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2010-12-02
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether nilotinib is effective in the prophylaxis and treatment of CMV reactivation in allo-HSCT patients.

Detailed description: The purpose of this study is to determine whether nilotinib is effective in the prophylaxis and treatment of CMV reactivation in allo-HSCT patients.

Prophylaxis Part: patients will be treated with nilotinib after their hemogram engraftment to prevent CMV reactivation Salvage Part: patients who have had intractable CMV reactivation after gancyclovir therapy will be treated with nilotinib

Eligibility criteria: Inclusion Criteria:

Part A:

* Adult patients who have received allo-HSCT
* Performance status ECOG 0-2
* Patients with CMV reactivation (defined as plasma CMV DNA copy numbers of more than 1000 copy numbers/ml by Quantitative-PCR) after allo-HSCT.
* Patients with CMV reactivation that is uncontrollable by conventional first line agent (ganciclovir) for 2 or more weeks, or patients who are intolerable to ganciclovir treatment.

Part B

* Adult patients who have received allo-HSCT
* Performance status ECOG 0-2
* Either the patient or his/her donor are CMV-IgG test positive
* Patients with post-transplantation engraftment: stable myeloid engraftment (absolute neutrophil count 500/mm3) for at least 3 consecutive days, and stable megakaryocyte engraftment (platelet count 20k/uL) for at least 3 consecutive days.
* Patient with no CMV reactivation before enrollment: a negative (undetectable) plasma CMV DNA Quantitative-PCR assay on blood collected within 7 days Patients without previous or current exposure to any prophylactic or therapeutic drugs for CMV reactivation

Exclusion Criteria:

* Patients with renal insufficiency: serum creatinine \> 2.5 mg/dL,
* Patients with significant electrolyte deficiency after suitable supplement: \[K\] \<3.0mmol/L, \[Ca\]\< 2.0 mmol/L(corrected), or \[Mg\] \< 0.6 mmol/L.
* Patients with hepatic dysfunction: alkaline phosphatase ≥2.5 times of the upper normal limit of the normal range (ULN); serum alanine or aspartate aminotransferase levels of \> 5 times ULN; a serum total bilirubin of \> 3 mg/dL
* Patients with serum amylase and lipase \> 1.5 x ULN
* Patients with history of HIV infection
* Patients with unstable medical condition or any other history of serious/significant medical diseases deemed not appropriate to be included to this study as judged by investigators
* Females patient who are pregnant or breast-feeding
* Female patients of childbearing potential not using any reliable and appropriate contraception method(s)
* Patients with life expectancy, as judged by the investigators, is less than 3 months
* Patients with, as judged by the investigators, other contraindications of nilotinib administration, such as prolonged QTc, concurrent usage of drugs that possess possible severe drug-drug interactions with nilotinib, or had severe adverse effects in the previous exposure to nilotinib
* Patients who cannot swallow capsules.
* Patients who are unwilling or unable to give consent

Primary outcomes:
measure: anti-CMV treatment free rate
timeFrame: 100 days after allo-HSCT (Day+100)
Secondary outcomes:
measure: Successful salvage rate
timeFrame: up to 8 weeks
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Shang-Ju Wu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lin CT, Hsueh PR, Wu SJ, Yao M, Ko BS, Li CC, Hsu CA, Tang JL, Tien HF. Repurposing Nilotinib for Cytomegalovirus Infection Prophylaxis after Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Arm, Phase II Trial. Biol Blood Marrow Transplant. 2018 Nov;24(11):2310-2315. doi: 10.1016/j.bbmt.2018.07.013. Epub 2018 Jul 17.