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Leflunomide to Prevent Cytomegalovirus Reactivation in Stem Cell Transplant Patients

11. juli 2026 opdateret af: 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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

22

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

Studiesteder

  • Indien
    • Maharashtra
      • Navi Mumbai, Maharashtra, Indien, 410210
        • Rekruttering
        • Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) Tata Memorial Centre
        • Kontakt:
        • Kontakt:
        • Ledende efterforsker:
          • Lingaraj Nayak, MD, DM
        • Underforsker:
          • Sumeet Mirgh, MD, DM
      • Navi Mumbai, Maharashtra, Indien, 410210
        • Ikke rekrutterer endnu
        • Advanced Centre for Treatment, Research and Education in Cancer
        • Kontakt:
        • Kontakt:
        • Ledende efterforsker:
          • Dr Lingaraj Nayak, MBBS MD DM Medical Oncology

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Forebyggelse
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Medicin: 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of participants with clinically significant cytomegalovirus (CMV) infection
Tidsramme: 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).

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of participants with treatment-emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Tata Memorial Centre

Samarbejdspartnere

Indian Council of Medical Research

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

18. oktober 2024

Primær færdiggørelse (Anslået)

1. april 2029

Studieafslutning (Anslået)

1. april 2029

Datoer for studieregistrering

Først indsendt

25. januar 2025

Først indsendt, der opfyldte QC-kriterier

11. juli 2026

Først opslået (Faktiske)

16. juli 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

16. juli 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

11. juli 2026

Sidst verificeret

1. juli 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 901006

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

IPD-planbeskrivelse

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

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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