Leflunomide to Prevent Cytomegalovirus Reactivation in Stem Cell Transplant Patients

July 11, 2026 updated by: Dr Lingaraj Nayak, Tata Memorial Centre

Use of Leflunomide as Primary Prophylaxis Against Cytomegalovirus (CMV) Reactivation in Haploidentical Haematopoietic Stem Cell Transplant (HIT) - Single, Arm, Phase 2 Clinical Trial

Patients undergoing half-matched hematopoietic stem cell transplantation (HSCT) are at high risk of viral reactivation after bone marrow transplantation (BMT). The purpose of this study is to evaluate whether leflunomide can prevent cytomegalovirus (CMV) reactivation in these patients and to assess its safety.

The main questions it aims to answer are -

  1. Does leflunomide prevent cytomegalovirus (CMV) related organ damage?
  2. Does leflunomide prevent a rise in cytomegalovirus (CMV) copy number to more than 2000 copies/ml?
  3. Does leflunomide prevent the need to start pre-emptive therapy for cytomegalovirus (CMV)?
  4. Is it safe to use in bone marrow transplant ( BMT) patients?
  5. Does leflunomide prevent other viral reactivations - like Adeno virus and BK virus?
  6. Does leflunomide affect the risk of acute graft-versus-host disease ( acute GVHD) after bone marrow transplant (BMT)?

What medicine will the patients receive? Patients in study shall receive loading dose of Tab. Leflunomide 100 mg daily for 3 days followed by 20 mg daily orally. Leflunomide will be given till day +180 post transplant or till patient is on immunosuppressant medicines.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Introduction :While pre-emptive medications have lowered the frequency of cytomegalovirus (CMV) illness after HSCT, CMV reactivation remains associated with higher mortality. Haploidentical transplant (haplo-HSCT) are high risk transplants, which have increased risk of viral reactivations. Current antiviral treatments, such as ganciclovir, have serious adverse effects and are limited in their use, whereas letermovir is expensive and unavailable in India.

Leflunomide, a medicine, which is used in Rheumatoid arthritis, is a possible alternative due to its antiviral effects and low cost. It may be beneficial at preventing cytomegalovirus (CMV) reactivation, particularly in patients with low viral levels. Furthermore, leflunomide has demonstrated efficacy against BK virus and other DNA viruses, making it a possible multifaceted preventive treatment for high-risk haplo-identical hematopoietic stem cell transplantation (HSCT) recipients.

Hypothesis Leflunomide is effective in decreasing clinically significant CMV(cytomegalovirus) infection after haplo-hematopoietic stem cell transplantation (HSCT)

Target population Patients ≥18 years of age who are undergoing haplo-hematopoietic stem cell transplantation (HSCT) for any malignancy at Tata Memorial centre ACTREC, Mumbai

Aims:

To evaluate efficacy of leflunomide as a prophylactic agent against cytomegalovirus (CMV)reactivation in Haplo-hematopoietic stem cell transplantation (HSCT).

Objectives -

Primary objective To determine the rate of clinically significant CMV infection on prophylactic leflunomide in haplo-HSCT patients till day+180 post HSCT

Secondary objective

  1. To evaluate the safety of post-transplant leflunomide using CTCAE 5.0 grading.
  2. To evaluate the incidence of clinically significant BK virus reactivation in peripheral blood and urine till day+180. Clinically significant BK virus reactivation will be defined as per ECIL-6 guidelines as more than 10^7 copies (7 log10 gEq/mL) in urine and 10^3 copies (1000 gEq/mL) in blood will be considered significant thresholds to define BK virus re- activation
  3. To evaluate the incidence of grade III - IV acute GVHD.

Study schema - Single-arm, Phase 2, prospective, interventional study

Administration of study treatment Once neutrophil engraftment has occurred i.e., ANC≥500/mm (on or before day-28), all patients in study shall receive loading dose of Tab. Leflunomide 100 mg daily for 3 days followed by 20 mg daily orally. Leflunomide will be given till day +180 post haplo-HSCT or till patient is on systemic immunosuppression

Timing of dose administration Study therapy should be administered/taken at the same time each day. Tablets are to be swallowed whole (i.e., no crushing or chewing the tablet is allowed). Study therapy may be administered with or without food. If a subject misses a dose, the missed dose should be given as soon as possible during the same day. If more than 18 hours have gone by after the regular dosing time, then the missed dose should be skipped and the normal dosing schedule should be resumed. The next dose should not be doubled in order to "make up" what has been missed.

Investigations During Treatment Monitoring: Weekly cytomegalovirus (CMV) PCR in blood, bi-weekly BK virus PCR in blood and urine, and additional tests as clinically indicated.

Overall study duration - 5 years

Study Type

Interventional

Enrollment (Estimated)

22

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
    • Maharashtra
      • Navi Mumbai, Maharashtra, India, 410210
        • Recruiting
        • Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) Tata Memorial Centre
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lingaraj Nayak, MD, DM
        • Sub-Investigator:
          • Sumeet Mirgh, MD, DM
      • Navi Mumbai, Maharashtra, India, 410210
        • Not yet recruiting
        • Advanced Centre for Treatment, Research and Education in Cancer
        • Contact:
        • Contact:
        • Principal Investigator:
          • Dr Lingaraj Nayak, MBBS MD DM Medical Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Males or females undergoing Haplo-identical haematopoetic stem cell transplant.
  2. Age ≥18yrs on the day of signing informed consent
  3. Undetectable CMV from plasma sample in preceding 7 days
  4. Patient who has WBC engraftment (ANC>=500/cumm for 3 or more consecutive days).
  5. Within 7 days of WBC engraftment
  6. Adequate liver functions (ALT / AST less than 5 times upper limit of normal and Bilirubin <=3 times upper limit of normal) at time of starting leflunomide
  7. Understands the study procedures, alternative treatment available, and risks involved with the study, and voluntarily agree to participate by giving written informed consent.

Exclusion Criteria:

  1. Known hypersensitivity to Leflunomide
  2. History of clinically significant CMV reactivation in past 1 year
  3. Patient is receiving/has received drug known to have anti CMV activity within in last 7 days [Ganciclovir, valganciclovir, foscarnet, letermovir, acyclovir (at doses >=3200 mg PO per day or >=25 mg/kg IV per day), valacyclovir (at doses &>=3000 mg PO per day)]
  4. Inadequate renal function (creatinine clearance <=30 ml/min)
  5. Chronic active hepatitis B (HBsAg+ or any HBV DNA+), hepatitis C, or/and HIV
  6. Any psychiatric condition that might limit the ability of the patient to comply with the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Leflunomide
This will be a single arm open label intervention study. Patients who undergo haploidentical transplant, within 7 days of engraftment, will receive leflunomide till day+180 post transplant or till patient is on systemic immunosuppression.
Drug: Leflunomide 20 mg
Patients in study shall receive loading dose of Tab Leflunomide 100 mg daily for 3 days followed by 20 mg daily orally. Leflunomide will be given till day 180 + post haploidentical transplant or till patient is on systemic immunosuppression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with clinically significant cytomegalovirus (CMV) infection
Time Frame: Through Day +180 post hematopoietic stem cell transplantation (HSCT).

Number of participants with clinically significant cytomegalovirus (CMV) infection through Day +180 after hematopoietic stem cell transplantation (HSCT). Clinically significant CMV infection is defined as the occurrence of one or more of the following:

Cytomegalovirus (CMV) end-organ disease; Cytomegalovirus (CMV) viremia ≥2,000 copies/mL measured by the central laboratory; or Initiation of pre-emptive anti-CMV therapy at the investigator's discretion.
Through Day +180 post hematopoietic stem cell transplantation (HSCT).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Time Frame: Day+180 post transplant
Number of participants experiencing treatment-emergent adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Day+180 post transplant
Number of participants with clinically significant BK virus reactivation
Time Frame: Day+180 post transplant

Number of participants with clinically significant BK virus reactivation through Day +180 after hematopoietic stem cell transplantation. Clinically significant BK virus reactivation is defined according to European Conference on Infections in Leukaemia (ECIL)-6 criteria as:

Urine BK viral load >10⁷ copies/mL (>7 log₁₀ genome equivalents/mL), or Blood BK viral load >10³ copies/mL (>1,000 genome equivalents/mL).
Day+180 post transplant
Number of participants with Grade III-IV acute graft-versus-host disease
Time Frame: Day+180 post transplant
Number of participants who develop Grade III-IV acute graft-versus-host disease (aGVHD) according to the study-defined grading criteria.
Day+180 post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tata Memorial Centre

Collaborators

Indian Council of Medical Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 18, 2024

Primary Completion (Estimated)

April 1, 2029

Study Completion (Estimated)

April 1, 2029

Study Registration Dates

First Submitted

January 25, 2025

First Submitted That Met QC Criteria

July 11, 2026

First Posted (Actual)

July 16, 2026

Study Record Updates

Last Update Posted (Actual)

July 16, 2026

Last Update Submitted That Met QC Criteria

July 11, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 901006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

At this time, we do not plan to share individual participant data (IPD) due to concerns regarding patient privacy, the regulatory requirements for data sharing for maintaining patient confidentiality

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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