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Hematologic MalignanciesPhase 2NCT07709013

Leflunomide to Prevent Cytomegalovirus Reactivation in Stem Cell Transplant Patients

A Phase 2 study testing Leflunomide 20 mg in people with Hematologic Malignancies, run by Tata Memorial Centre at 3 sites in India.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hematologic Malignancies
What is being tested?
Leflunomide 20 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
3 sitesIndia
Study dates
18 Oct 2024to Apr 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males or females undergoing Haplo-identical haematopoetic stem cell transplant.
  • Age ≥18yrs on the day of signing informed consent
  • Undetectable CMV from plasma sample in preceding 7 days
  • Patient who has WBC engraftment (ANC>=500/cumm for 3 or more consecutive days).
  • Within 7 days of WBC engraftment
  • 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
  • Understands the study procedures, alternative treatment available, and risks involved with the study, and voluntarily agree to participate by giving written informed consent.

Who cannot join

  • Known hypersensitivity to Leflunomide
  • History of clinically significant CMV reactivation in past 1 year
  • 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)]
  • Inadequate renal function (creatinine clearance <=30 ml/min)
  • Chronic active hepatitis B (HBsAg+ or any HBV DNA+), hepatitis C, or/and HIV
  • Any psychiatric condition that might limit the ability of the patient to comply with the protocol

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Lingaraj Nayak, MD, DM contact

91-9167294976

lingarajnayak86@gmail.com

Sumeet Mirgh, MD, DM contact

91-8130140245

drsumeetmirgh@gmail.com

India3 sites, 3 recruiting
  • Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) Tata Memorial Centre

    Navi Mumbai, Maharashtra, 410210

    Lingaraj Nayak, MD, DM, 91-9167294976, lingarajnayak86@gmail.com

    Sumeet Mirgh, MD, DM, 91-8130140245, drsumeetmirgh@gmail.com

    Recruiting
  • Advanced Centre for Treatment, Research and Education in Cancer

    Navi Mumbai, Maharashtra, 410210

    Lingaraj Nayak Nayak L, MBBS,MD DM Medical Oncology, +91-22- 24177000 ext. 7210, lingarajnayak86@gmail.com

    Not yet recruiting
  • Advanced Centre for Treatment, Research and Education in Cancer

    Navi Mumbai, Maharashtra, 410210

    Dr. Lingaraj Nayak, MBBS,MD DM Medical Oncology, 91 22 24177000 ext. 7210, lingarajnayak86@gmail.com

    Dr Sumeet Mirgh, DM medical Oncology, drsumeetmirgh@gmail.com

    Not yet recruiting

Other trials in India

About this study

Official title: 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 -

Read more
  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.

Read the 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

Being tested
Leflunomide 20 mg
Keywords
Cytomegalovirus (CMV) Reactivation, Leflunomide, haplo-HSCT, Haploidentical, Hematopoietic stem cell transplant
Medical subject headings
Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Leflunomide 20 mgDrug

    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.

Study groups in NCT07709013
Study groupRoleWhat they receive
LeflunomideExperimentalThis 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.
Receives: Drug: Leflunomide 20 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with clinically significant cytomegalovirus (CMV) infection

    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.

    Measured: Through Day +180 post hematopoietic stem cell transplantation (HSCT).

Secondary outcomes (3)
  1. Number of participants with treatment-emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

    Number of participants experiencing treatment-emergent adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

    Measured: Day+180 post transplant

  2. Number of participants with clinically significant BK virus reactivation

    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).

    Measured: Day+180 post transplant

  3. Number of participants with Grade III-IV acute graft-versus-host disease

    Number of participants who develop Grade III-IV acute graft-versus-host disease (aGVHD) according to the study-defined grading criteria.

    Measured: Day+180 post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2026
  2. Study start18 Oct 2024
  3. Primary completionApr 2029 (estimated)
  4. Study completionApr 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Model description
Single-arm, Phase 2, prospective, interventional study.
Masking
None (open label)
Enrolment
22 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07709013
Sponsor's protocol ID
901006
Status last verified
Jul 2026
First submitted
25 Jan 2025
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: 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

Publications

  • PREVYMIS™ (letermovir) Whitehouse Station, NJ: Merck &amp; Co., Inc.; 2017

  • Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, Pikis A, Razonable RR, Miller V, Griffiths PD; Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis. 2017 Jan 1;64(1):87-91. doi: 10.1093/cid/ciw668. Epub 2016 Sep 28.

    PubMed 27682069
  • Fox R, Helfgott S (2021). Leflunomide. In St Clair EW (Ed.), UpToDate. https://www.uptodate.com/drug-interactions. Accessed June 01, 2023

  • Strand V, Cohen S, Schiff M, Weaver A, Fleischmann R, Cannon G, Fox R, Moreland L, Olsen N, Furst D, Caldwell J, Kaine J, Sharp J, Hurley F, Loew-Friedrich I. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch Intern Med. 1999 Nov 22;159(21):2542-50. doi: 10.1001/archinte.159.21.2542.

    PubMed 10573044
  • US Department of Health and Human Services, National Institutes of Health, National Cancer Institute (2017) Common Terminology Criteria for Adverse Events (CTCAE) Version Study protocol Version -1.1 dated 22/02/2024 17 of 16 5.0 2017. https://ctep.cancer.gov/ protocolDevelopment/electronic_applications/docs/ CTCAE_v5_Quick_Reference_8.5x11.pdf. Accessed 01 May 2020

  • Matthes-Martin S, Feuchtinger T, Shaw PJ, Engelhard D, Hirsch HH, Cordonnier C, Ljungman P; Fourth European Conference on Infections in Leukemia. European guidelines for diagnosis and treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL-4 (2011). Transpl Infect Dis. 2012 Dec;14(6):555-63. doi: 10.1111/tid.12022. Epub 2012 Nov 12.

    PubMed 23146063
  • Lindemans CA, Leen AM, Boelens JJ. How I treat adenovirus in hematopoietic stem cell transplant recipients. Blood. 2010 Dec 16;116(25):5476-85. doi: 10.1182/blood-2010-04-259291. Epub 2010 Sep 13.

    PubMed 20837781
  • Anderson EJ, Guzman-Cottrill JA, Kletzel M, Thormann K, Sullivan C, Zheng X, Katz BZ. High-risk adenovirus-infected pediatric allogeneic hematopoietic progenitor cell transplant recipients and preemptive cidofovir therapy. Pediatr Transplant. 2008 Mar;12(2):219-27. doi: 10.1111/j.1399-3046.2007.00851.x.

    PubMed 18307672
  • Jeffers-Francis LK, Burger-Calderon R, Webster-Cyriaque J. Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system. Antiviral Res. 2015 Jun;118:46-55. doi: 10.1016/j.antiviral.2015.02.002. Epub 2015 Mar 16.

    PubMed 25790744
  • Cesaro S, Dalianis T, Hanssen Rinaldo C, Koskenvuo M, Pegoraro A, Einsele H, Cordonnier C, Hirsch HH; ECIL-6 Group. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients. J Antimicrob Chemother. 2018 Jan 1;73(1):12-21. doi: 10.1093/jac/dkx324.

    PubMed 29190347
  • Bogdanovic G, Priftakis P, Giraud G, Kuzniar M, Ferraldeschi R, Kokhaei P, Mellstedt H, Remberger M, Ljungman P, Winiarski J, Dalianis T. Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation. J Clin Microbiol. 2004 Nov;42(11):5394-6. doi: 10.1128/JCM.42.11.5394-5396.2004.

    PubMed 15528753
  • Erard V, Kim HW, Corey L, Limaye A, Huang ML, Myerson D, Davis C, Boeckh M. BK DNA viral load in plasma: evidence for an association with hemorrhagic cystitis in allogeneic hematopoietic cell transplant recipients. Blood. 2005 Aug 1;106(3):1130-2. doi: 10.1182/blood-2004-12-4988. Epub 2005 Apr 21.

    PubMed 15845896
  • Bernhoff E, Tylden GD, Kjerpeseth LJ, Gutteberg TJ, Hirsch HH, Rinaldo CH. Leflunomide inhibition of BK virus replication in renal tubular epithelial cells. J Virol. 2010 Feb;84(4):2150-6. doi: 10.1128/JVI.01737-09. Epub 2009 Dec 2.

    PubMed 19955306
  • Nesselhauf N, Strutt J, Bastani B. Evaluation of leflunomide for the treatment of BK viremia and biopsy proven BK nephropathy; a single center experience. J Nephropathol. 2016 Jan;5(1):34-7. doi: 10.15171/jnp.2016.06. Epub 2015 Dec 23.

    PubMed 27047808
  • Chacko B, John GT. Leflunomide for cytomegalovirus: bench to bedside. Transpl Infect Dis. 2012 Apr;14(2):111-20. doi: 10.1111/j.1399-3062.2011.00682.x. Epub 2011 Oct 9.

    PubMed 22093814

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Leflunomide 20 mg in people with Hematologic Malignancies, run by Tata Memorial Centre at 3 sites in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lingaraj Nayak, MD, DM (91-9167294976, lingarajnayak86@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with clinically significant cytomegalovirus (CMV) infection (time frame: Through Day +180 post hematopoietic stem cell transplantation (HSCT).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07709013, which also lists 29 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026.

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