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Myelodysplastic SyndromesPhase 1/2NCT06923488

Leflunomide in Combination With Decitabine for Treatment of Relapsed or Refractory Myelodysplastic Syndromes

A Phase 1/2 study testing Leflunomide 10mg, Leflunomide 20mg and Decitabine in people with Myelodysplastic Syndromes, run by West Virginia University at 1 site in United States.

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

The goal of this interventional clinical trial is to evaluate the safety and tolerability of leflunomide in combination with decitabine as treatment for patients with relapsed or refractory myelodysplastic syndromes (R/R MDS). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
Leflunomide 10mg, Leflunomide 20mg and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
15 Jul 2025to Oct 2028
Phase
Phase 1/2
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

  • Patient has pathologically confirmed diagnosis of MDS
  • Patient has currently measurable disease meeting the following criteria:
  • Bone marrow biopsy with more than 5% blasts, AND
  • Absolute neutrophil count (ANC) less than 1,000/mcL, and/or platelet count less than 100,000/mcL and/or hemoglobin levels less than 10g/dL
  • Patient has received one prior treatment with a DNA methyltransferase inhibitor (DNMTi), also commonly called hypomethylating agent (HMA). Patients whose MDS has IDH1/IDH2 mutations should have received at least one available IDH1/IDH2 inhibitor
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
Show all 13Show fewer
  • Patient has the following required baseline laboratory data (eligibility can be based on local lab results):
  • Total serum bilirubin level less than or equal to 2 times ULN
  • Estimated glomerular filtration rate (eGFR) greater than or equal to 45 mL/min/1.73 m2
  • Patients who have undergone alloHSCT are eligible if they are more than 28 days post stem cell infusion, have no evidence of GVHD > Grade 1, and are more than a week off all immunosuppressive therapy
  • If a female of childbearing potential, the patient has a negative serum or urine pregnancy test result within 7 days prior to the first dose of treatment. Women of non-childbearing potential are those who are postmenopausal greater than one year or who have had a bilateral tubal ligation or hysterectomy
  • If female of childbearing potential or a male patient, patient agrees to use an effective contraceptive method from the time of informed consent, during the course of the study, and for 3 months following the last dose of treatment
  • Patient understands and voluntarily signs the written informed consent prior to any study-specific procedures. A copy of the signed informed consent form will be retained by the treating institution

Who cannot join

  • Patients receiving any other investigational agents, or concurrent chemotherapy or immunotherapy
  • Patients with progression to acute myeloid leukemia
  • Patients with other malignancies requiring systemic chemotherapy, immunotherapy or targeted therapy in the last four weeks
  • Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms)
  • Patients with active or latent tuberculosis
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that per Principal Investigator's judgment would limit compliance with study requirements
  • Females who are pregnant or breast feeding
  • Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study

Trial locations and contacts

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

Konstantinos Sdrimas, MD contact

304-598-4520

Konstantinos.sdrimas1@hsc.wvu.edu

United States1 site, 1 recruiting

  • West Virginia University Cancer Institute

    Morgantown, West Virginia, 26506

    Recruiting

Other trials in United States

About this study

Official title: Phase I/II Study of Leflunomide in Combination With Decitabine for Treatment of Relapsed or Refractory (R/R) Myelodysplastic Syndromes (MDS)

The goal of this interventional clinical trial is to evaluate the safety and tolerability of leflunomide in combination with decitabine as treatment for patients with relapsed or refractory myelodysplastic syndromes (R/R MDS).

The main question this study aims to answer are to evaluate and estimate the maximum tolerated doses and/or biologically active doses of the combination of leflunomide-decitabine in participants.

Decitabine will be administered at a dose of 20 mg/m2 by continuous intravenous infusion over one hour repeated daily for 5 days with repeating cycle every 4 weeks. Leflunomide is administered orally at 10 to 20 mg once daily (without a loading dose) for 14 to 21 days, as part of a 28-day treatment cycle in adult subjects with R/R MDS. After 12 cycles (study duration) responding patients can continue progression with the assigned doses.

Read the detailed description

This is a phase I/II dose-escalation trial to estimate the activity of leflunomide in combination with decitabine for treatment of relapsed or refractory MDS. Leflunomide will be administered orally daily with decitabine IV for 5 days as part of a 28-day treatment cycle in adult subjects with R/R MDS. Patients who have been previously treated with decitabine will be eligible. The trial will consist of dose escalation to evaluate safety and tolerability of leflunomide in combination with decitabine. There will be no intra-patient dose escalation or reduction. In the event of an RLT, one or both drugs (leflunomide or decitabine) could be withheld at the discretion of the treating physician and on the basis of the expected adverse event. The period for determination of RLT will be from the first day of treatment until 30 days after receiving the first dose of leflunomide + decitabine. After 12 cycles (study duration) responding patients can continue progression with the assigned doses.

Staging studies, including bone marrow biopsy and complete blood counts will be performed within 45 days prior to study enrollment and again within 30 days after completing Cycle 3, Cycle 6, and Cycle 12 and within 30 days of discontinuing study treatment. A repeat bone marrow biopsy will be performed at the end of the study (Cycle 12). Patients will be followed every 3 months for 2 years after completion of study.

Study assessments will also include monitoring of all toxicities and adverse events. The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, will be used for grading adverse events and all toxicities

Being tested
Leflunomide 10mg, Leflunomide 20mg, Decitabine
Keywords
relapsed or refractory
Medical subject headings
Myelodysplastic Syndromes, Recurrence

What participants receive

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

  • Leflunomide 10mgDrug

    Also called Arava

    Leflunomide 10mg tablet

  • Leflunomide 20mgDrug

    Also called Arava

    Leflunomide 20mg tablet

  • DecitabineDrug

    Also called Dacogen

    Decitabine dose of 20 mg/m2

Study groups in NCT06923488
Study groupRoleWhat they receive
Leflunomide + Decitabine TreatmentExperimentalParticipants will receive combination treatment for 12 cycles consisting of 28 days. Utilizing a conventional 3+3 design, Decitabine will be at a dose of 20 mg/m2 and will be administered by intravenous infusion over 1 hour daily for 5 days each 28-day cycle. Leflunomide will have a dose escalation schedule starting at (Level +1) as follows: Dose Escalation (Level -2): Leflunomide 10mg once daily by mouth x 14 days/cycle (Level -1): Leflunomide 10mg once daily by mouth x 21 days/cycle (Level +1): Leflunomide 20mg once daily by mouth x 14 days/cycle (Level +2): Leflunomide 20mg once daily by mouth x 21 days/cycle
Receives: Drug: Leflunomide 10mg; Drug: Leflunomide 20mg; Drug: Decitabine

What is being measured

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

  1. Percentage of incidences of regimen limiting toxicities (RLTs)

    Percentages of incidences of RLTs defined as:

    • A need to reduce the dose of one or both of the treatments
    • Discontinue the treatment due to dose limiting toxicities, AE/SAE
    • Be withheld at the discretion of the treating physician and on the basis of the expected adverse event

    Measured: Date of first treatment up to 13 months

Secondary outcomes (15)

  1. Percentage of Complete Remission (CR) Rate (3rd cycle)

    Percentage of patients achieving complete remission (CR) rate defined as bone marrow (BM): <5% myeloblasts (dysplasia may persist), and peripheral blood (PB): hemoglobin (Hb) ≥10 g/dL, platelets ≥100 × 109/L; neutrophils ≥1.0 × 109/L; blasts 0%. Full cytogenetic clearance of baseline abnormalities (complete cytogenetic response)

    Measured: Within 30 days following the end of the 3rd cycle (cycle = 28 days)

  2. Percentage of Complete Remission (CR) Rate (6th cycle)

    Percentage of patients achieving complete remission (CR) rate defined as bone marrow (BM): <5% myeloblasts (dysplasia may persist), and peripheral blood (PB): hemoglobin (Hb) ≥10 g/dL, platelets ≥100 × 109/L; neutrophils ≥1.0 × 109/L; blasts 0%. Full cytogenetic clearance of baseline abnormalities (complete cytogenetic response)

    Measured: Within 30 days following the end of the 6th cycle (cycle = 28 days)

  3. Percentage of Complete Remission (CR) Rate (12th cycle)

    Percentage of patients achieving complete remission (CR) rate defined as bone marrow (BM): <5% myeloblasts (dysplasia may persist), and peripheral blood (PB): hemoglobin (Hb) ≥10 g/dL, platelets ≥100 × 109/L; neutrophils ≥1.0 × 109/L; blasts 0%. Full cytogenetic clearance of baseline abnormalities (complete cytogenetic response)

    Measured: Within 30 days of the end of the 12th cycle (cycle = 28 days)

  4. CR + complete remission with partial hematologic recovery (CRh) (3rd cycle)

    Percentage of participants that achieve CR + complete remission with partial hematologic recovery (CRh) - defined as BM: <5% myeloblasts (dysplasia may persist) and PB: Not meeting criteria for CR or CRL, no Hb threshold required, platelets ≥50 × 109/L; neutrophils ≥0.5 × 109/L; blasts 0%

    Measured: Within 30 days following the end of the 3rd cycle (cycle = 28 days)

  5. CR + complete remission with partial hematologic recovery (CRh) (6th cycle)

    Percentage of participants that achieve CR + complete remission with partial hematologic recovery (CRh) - defined as BM: <5% myeloblasts (dysplasia may persist) and PB: Not meeting criteria for CR or CRL, no Hb threshold required, platelets ≥50 × 109/L; neutrophils ≥0.5 × 109/L; blasts 0%

    Measured: Within 30 days following the end of the 6th cycle (cycle = 28 days)

  6. CR + complete remission with partial hematologic recovery (CRh) (12th cycle)

    Percentage of participants that achieve CR + complete remission with partial hematologic recovery (CRh) - defined as BM: <5% myeloblasts (dysplasia may persist) and PB: Not meeting criteria for CR or CRL, no Hb threshold required, platelets ≥50 × 109/L; neutrophils ≥0.5 × 109/L; blasts 0%

    Measured: Within 30 days following the end of the 12th cycle (cycle = 28 days)

  7. CR + CRh + complete remission with limited count recovery (CRL) including CR bilineage (CRbi) and CR unilineage (CRuni) (3rd cycle)

    Percentage of participants that achieve CR + CRh + complete remission with limited count recovery (CRL) including CR bilineage (CRbi) and CR unilineage (CRuni) - defined as BM: <5% myeloblasts (dysplasia may persist), and PB: blasts 0%; CRuni: PB, not meeting CR but only 1 of the following: Hb ≥10 g/dL; platelets ≥100 × 109/L; neutrophils ≥1.0 × 109/L; CRbi: PB, not meeting CR but only 2 of the following: Hb ≥10 g/dL; platelets ≥100 × 109/L; neutrophils ≥1.0 × 109/L

    Measured: Within 30 days following the end of the 3rd cycle (cycle = 28 days)

  8. CR + CRh + complete remission with limited count recovery (CRL) including CR bilineage (CRbi) and CR unilineage (CRuni) (6th cycle)

    Percentage of participants that achieve CR + CRh + complete remission with limited count recovery (CRL) including CR bilineage (CRbi) and CR unilineage (CRuni) - defined as BM: <5% myeloblasts (dysplasia may persist), and PB: blasts 0%; CRuni: PB, not meeting CR but only 1 of the following: Hb ≥10 g/dL; platelets ≥100 × 109/L; neutrophils ≥1.0 × 109/L; CRbi: PB, not meeting CR but only 2 of the following: Hb ≥10 g/dL; platelets ≥100 × 109/L; neutrophils ≥1.0 × 109/L

    Measured: Within 30 days following the end of the 6th cycle (cycle = 28 days)

  9. CR + CRh + complete remission with limited count recovery (CRL) including CR bilineage (CRbi) and CR unilineage (CRuni) (12th cycle)

    Percentage of participants that achieve CR + CRh + complete remission with limited count recovery (CRL) including CR bilineage (CRbi) and CR unilineage (CRuni) - defined as BM: <5% myeloblasts (dysplasia may persist), and PB: blasts 0%; CRuni: PB, not meeting CR but only 1 of the following: Hb ≥10 g/dL; platelets ≥100 × 109/L; neutrophils ≥1.0 × 109/L; CRbi: PB, not meeting CR but only 2 of the following: Hb ≥10 g/dL; platelets ≥100 × 109/L; neutrophils ≥1.0 × 109/L

    Measured: Within 30 days following the end of the 12th cycle (cycle = 28 days)

  10. Allogeneic hematopoietic stem cell transplant (alloHSCT)

    The percentage of participants that proceed to allogeneic hematopoietic stem cell transplant (alloHSCT).

    Measured: Enrollment up to 3 years

  11. Overall Survival (OS)

    Overall Survival (OS) defined for all patients of the trial; measured from the first day of receiving study drugs on the clinical trial to the date of death by any cause

    Measured: From first treatment up to 3 years

  12. Event-free survival (EFS)

    Event-free survival (EFS) defined for all patients of the trial; measured from the first day of receiving study drugs to the date of treatment failure, or relapse from CR or CRh or CRL, or death by any cause. Treatment is defined as failure to achieve CR or CRh or CRL after at least three cycles of treatment; the date of treatment failure is defined as date of marrow evaluation after the last course of treatment.

    Measured: From first treatment up to 3 years

  13. Relapse-free survival (RFS) defined only for patients achieving CR or CRh or CRL;

    Relapse-free survival (RFS) defined only for patients achieving CR or CRh or CRL; measured from the date of achievement of a CR/CRh/CRL until the date of relapse or death from any cause; RFS and disease-free survival (DFS) have been used with the same definition.

    Measured: From the date of achievement of a CR/CRh/CRL up to 3 years

  14. Progression to acute myeloid leukemia (AML)

    Percentage of participant progression to acute myeloid leukemia (AML)

    Measured: Enrollment up to 3 years

  15. Percentage of Red Blood Cell transfusion independence

    The percentage of participants that achieve the conversion from red blood cell transfusion dependence to transfusion independence. Transfusion Independence is defined as a period of time, usually 8 weeks, with no transfusion between first dose of study drug and the last dose of study drug + 30 days.

    Measured: Date of first treatment up to 3 years

Timeline

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

  1. First posted11 Apr 2025
  2. Study start15 Jul 2025
  3. Primary completionOct 2027 (estimated)
  4. Study completionOct 2028 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06923488
Sponsor's protocol ID
2502109808
Status last verified
Apr 2026
First submitted
25 Mar 2025
Last updated
23 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chilakala S, Feng Y, Li L, Mahfouz R, Quteba E, Saunthararajah Y, Xu Y. Tracking Decitabine Incorporation into Malignant Myeloid Cell DNA in vitro and in vivo by LC-MS/MS with Enzymatic Digestion. Sci Rep. 2019 Mar 14;9(1):4558. doi: 10.1038/s41598-019-41070-y.

    PubMed 30872721

  • Qin F, Wu J, Chen F, Wei Y, Zhao Y, Jiang Z, Bai J, Yu H. Optimal, minimax and admissible two-stage design for phase II oncology clinical trials. BMC Med Res Methodol. 2020 May 20;20(1):126. doi: 10.1186/s12874-020-01017-8.

    PubMed 32434577

  • Zeidan AM, Platzbecker U, Bewersdorf JP, Stahl M, Ades L, Borate U, Bowen D, Buckstein R, Brunner A, Carraway HE, Daver N, Diez-Campelo M, de Witte T, DeZern AE, Efficace F, Garcia-Manero G, Garcia JS, Germing U, Giagounidis A, Griffiths EA, Hasserjian RP, Hellstrom-Lindberg E, Iastrebner M, Komrokji R, Kulasekararaj AG, Malcovati L, Miyazaki Y, Odenike O, Santini V, Sanz G, Scheinberg P, Stauder R, van de Loosdrecht AA, Wei AH, Sekeres MA, Fenaux P. Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes. Blood. 2023 Apr 27;141(17):2047-2061. doi: 10.1182/blood.2022018604.

    PubMed 36724453

  • Kayamori K, Nagai Y, Zhong C, Kaito S, Shinoda D, Koide S, Kuribayashi W, Oshima M, Nakajima-Takagi Y, Yamashita M, Mimura N, Becker HJ, Izawa K, Yamazaki S, Iwano S, Miyawaki A, Ito R, Tohyama K, Lennox W, Sheedy J, Weetall M, Sakaida E, Yokote K, Iwama A. DHODH inhibition synergizes with DNA-demethylating agents in the treatment of myelodysplastic syndromes. Blood Adv. 2021 Jan 26;5(2):438-450. doi: 10.1182/bloodadvances.2020001461.

    PubMed 33496740

  • Santini V. How I treat MDS after hypomethylating agent failure. Blood. 2019 Feb 7;133(6):521-529. doi: 10.1182/blood-2018-03-785915. Epub 2018 Dec 13.

    PubMed 30545832

  • Stomper J, Rotondo JC, Greve G, Lubbert M. Hypomethylating agents (HMA) for the treatment of acute myeloid leukemia and myelodysplastic syndromes: mechanisms of resistance and novel HMA-based therapies. Leukemia. 2021 Jul;35(7):1873-1889. doi: 10.1038/s41375-021-01218-0. Epub 2021 May 6.

    PubMed 33958699

  • Jabbour E, Garcia-Manero G, Batty N, Shan J, O'Brien S, Cortes J, Ravandi F, Issa JP, Kantarjian H. Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer. 2010 Aug 15;116(16):3830-4. doi: 10.1002/cncr.25247.

    PubMed 20564137

  • Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8. Epub 2009 Feb 21.

    PubMed 19230772

  • Prebet T, Gore SD, Esterni B, Gardin C, Itzykson R, Thepot S, Dreyfus F, Rauzy OB, Recher C, Ades L, Quesnel B, Beach CL, Fenaux P, Vey N. Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure. J Clin Oncol. 2011 Aug 20;29(24):3322-7. doi: 10.1200/JCO.2011.35.8135. Epub 2011 Jul 25.

    PubMed 21788559

  • Zeidan AM, Stahl M, Hu X, Wang R, Huntington SF, Podoltsev NA, Gore SD, Ma X, Davidoff AJ. Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation. Blood. 2018 Feb 15;131(7):818-821. doi: 10.1182/blood-2017-10-811729. Epub 2017 Dec 19. No abstract available.

    PubMed 29259002

  • Bartenstein M, Deeg HJ. Hematopoietic stem cell transplantation for MDS. Hematol Oncol Clin North Am. 2010 Apr;24(2):407-22. doi: 10.1016/j.hoc.2010.02.003.

    PubMed 20359634

  • Sekeres MA, Schoonen WM, Kantarjian H, List A, Fryzek J, Paquette R, Maciejewski JP. Characteristics of US patients with myelodysplastic syndromes: results of six cross-sectional physician surveys. J Natl Cancer Inst. 2008 Nov 5;100(21):1542-51. doi: 10.1093/jnci/djn349. Epub 2008 Oct 28.

    PubMed 18957672

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Leflunomide 10mg, Leflunomide 20mg and Decitabine in people with Myelodysplastic Syndromes, run by West Virginia University at 1 site in United States.

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 13 inclusion and 8 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 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 Konstantinos Sdrimas, MD (304-598-4520, Konstantinos.sdrimas1@hsc.wvu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of incidences of regimen limiting toxicities (RLTs) (time frame: Date of first treatment up to 13 months). 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 NCT06923488, which also lists 12 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 23 Apr 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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