Nilotinib for Cytomegalovirus Prophylaxis and Treatment After Allogeneic Hematopoietic Stem Cell Transplantation

Cytomegalovirus (CMV) Reactivation in Post-allogeneic Hematopoietic Stem Cell Transplantation(Allo-HSCT) Patients: Salvage and Prophylactic Treatments of Nilotinib

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

Study Overview

• Status: Completed
• Conditions: Patients Who Have Received Allo-HSCT
• Intervention / Treatment: Drug: nilotinib

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

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Nilotinib; Single arm, open label study	Drug: nilotinib; nilotinib (200mg/tab) 1 tab everyday; Other Names: tasigna

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
anti-CMV treatment free rate	For prophylaxis part	100 days after allo-HSCT (Day+100)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful salvage rate	For salvage treatment part	up to 8 weeks

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Shang-Ju Wu, MD, National Taiwan University Hospital

Publications and helpful links

General Publications

• 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.

Helpful Links

• Published article

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2010
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: November 24, 2010
• First Submitted That Met QC Criteria: November 30, 2010
• First Posted (Estimate): December 2, 2010

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 201006057M