Clinical Trials /

NTX-301 in MDS/AML



NTX-301 is a DNMT1 inhibitor. The drug is an oral drug with preclinical data that has shown preclinical anti-leukemic efficacy. This is the first clinical trial using NTX-301 in patients with myeloid malignancies.

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:



Phase 1

Trial Eligibility



  • Brief Title: NTX-301 in MDS/AML
  • Official Title: A Phase 1 Study of NTX-301, an Oral DNMT1 Inhibitor, in Patients With MDS and AML

Clinical Trial IDs

  • NCT ID: NCT04167917


  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Chronic Myelomonocytic Leukemia




NTX-301 is a DNMT1 inhibitor. The drug is an oral drug with preclinical data that has shown preclinical anti-leukemic efficacy. This is the first clinical trial using NTX-301 in patients with myeloid malignancies.

Trial Arms

  • NTX-301

Eligibility Criteria

        Inclusion Criteria:

          1. Able to understand and comply with the study procedures, understand the risks involved
             in the study, and provide written informed consent before the first study-specific

          2. Men or women ≥18 years with one of the following conditions that is relapsed or
             refractory to at least one line of therapy:

               1. Acute myeloid leukemia as long as with myeloblast percentage in the marrow is ≤
                  30% or the peripheral white blood cell count is less than 20,000 cells/μL in the
                  absence of leukoreducing therapy (e.g., hydroxyurea, leukapheresis)

               2. MDS classified as intermediate, high, or very high risk by International
                  Prognostic Scoring System-Revised [IPSS-R] criteria

               3. CMML classified as intermediate-2 or high risk per CMML-specific prognostic
                  scoring system (CPSS) or clinical/molecular CPSS (CPSS-mol) criteria

          3. ECOG performance status of 0, 1, or 2

          4. Adequate organ function at screening defined as follows [reasonably minor changes
             pre-first dose are acceptable if deemed so by the investigator]:

             a) Hepatic:

               -  Total bilirubin ≤2 × upper limit of normal (ULN); isolated bilirubin > 2 is
                  acceptable if participant has a diagnosis of Gilbert's syndrome

               -  Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and
                  alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤3 × ULN.

                  b) Renal:

               -  estimated glomerular filtration rate (by CKD-EPI method) ≥ 40 mL/min/1.73 m2 c)

               -  Left ventricular ejection fraction greater than 45% or the institutional lower
                  limit of normal by either ECHO or MUGA at entry.

          5. Patients must have recovered to grade 1 or less from prior toxicity or adverse events
             (exception of myelosuppression - neutropenia, anemia, thrombocytopenia - and
             alopecia). Note: Participants with treatment-related toxicities that are unlikely to
             resolve per the investigator may be enrolled on a case-by-case basis after discussion
             with the medical monitor

          6. Patients must have completed any chemotherapy, radiation therapy, or biologic therapy
             specific to their myeloid neoplasm ≥ 2 weeks or 5 half-lives (whichever is longer)

          7. Able to swallow, retain, and absorb orally administered medication

          8. Expected life ≥ 4 months

          9. Participants with a prior history of stem cell transplant (autologous and/or
             allogeneic) are allowed if all of the following are met:

               -  90 days or more have elapsed from the time of transplant

               -  subject has been off systemic immunosuppressive medications (including but not
                  limited to: cyclosporine, tacrolimus, mycophenolate mofetil, or corticosteroids)
                  for at least 30 days prior to the first dose of NTX-301. Topical steroids are

               -  no signs or symptoms of acute graft versus host disease, other than Grade 1 skin

               -  there are no signs or symptoms of chronic graft versus host disease requiring
                  systemic therapy

         10. Women of child-bearing potential (according to recommendations of the Clinical Trial
             Facilitation Group [CTFG], CTFG 2014) must not be pregnant or breastfeeding and must
             have a negative pregnancy test at screening. A woman is considered of childbearing
             potential (ie, fertile) following menarche and until becoming postmenopausal, unless
             permanently sterile. Permanent sterilization methods include hysterectomy, bilateral
             salpingectomy, and bilateral oophorectomy. A man is considered fertile after puberty
             unless permanently sterile by bilateral orchidectomy.

         11. Subjects and their partners with reproductive potential must agree to use 2 highly
             effective contraceptive measures during the study and must agree not to become
             pregnant or father a child for 3 months after the last dose of study treatment.
             Contraceptive measures that may be considered highly effective comprise combined
             hormonal contraception (oral, vaginal, or transdermal) or progestogen-only hormonal
             contraception (oral, injectable, implantable) associated with inhibition of ovulation,
             intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion,
             sexual abstinence, and surgically successful vasectomy. Abstinence is acceptable only
             if it is consistent with the preferred and usual lifestyle of the subject. Periodic
             abstinence (eg, calendar, ovulation, symptothermal, or post-ovulation methods) and
             withdrawal are not acceptable methods of birth control.

        Exclusion Criteria:

          1. Diagnosis or presence of any of the following:

               -  acute promyelocytic leukemia

               -  core-binding factor AML in first relapse

               -  extramedullary leukemia

               -  symptomatic or untreated Central Nervous System (CNS) disease [note that lumbar
                  puncture (LP) is not required for study enrollment unless there is clinical
                  suspicion for CNS disease; patients with history of CNS disease are permitted to
                  enroll if they have previously received appropriate therapy and CNS remission has
                  been; participants on maintenance intrathecal chemotherapy may be enrolled and
                  continue to receive therapy]

          2. Patients who are receiving any other investigational agents.

          3. Pregnant women and women who are breastfeeding are excluded from this study.

          4. Patients with clinically significant illnesses which would compromise participation in
             the study, including, but not limited to:

               -  severe or uncontrolled infection

               -  known HIV infection requiring protease inhibitor therapy

               -  known Hepatitis B; defined as presence of hepatitis B surface antigen (HBsAg)

               -  known Hepatitis C; if Hepatitis C antibody is positive, then this is defined as
                  positive Hepatitis C RNA polymerase chain reaction (PCR) (or comparable test)

               -  uncontrolled diabetes and/or hypertension, symptomatic congestive heart failure,
                  unstable angina pectoris, myocardial infarction within the past 6 months,
                  uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that
                  would limit compliance with study requirements in the opinion of the investigator

               -  Malabsorption syndrome or other conditions that would interfere with intestinal

          5. History of a second malignancy, excluding non-melanoma skin cell cancer, within the
             last three years. Participants with second malignancies that were indolent, in situ or
             definitively treated may be enrolled even if less than three years have elapsed since
             treatment. Consult the monitor if there are any queries.

          6. History of prior solid organ transplant

          7. History of prior sensitivity reaction to any cytidine derivates
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety/tolerability: Incidence of treatment related adverse events (AEs) and dose-limiting toxicities (DLTs)
Time Frame:3 years
Safety Issue:

Secondary Outcome Measures

Measure:Efficacy: Clinical Benefit Rate (CBR)
Time Frame:3 years
Safety Issue:
Description:Clinical Benefit Rate (CBR), as defined as the percentage of participants achieving a complete remission (CR), complete marrow remission (mCR), partial remission (PR), stable disease (SD) lasting at least 8 weeks, or hematologic improvement (HI), per International Working Group (IWG) criteria.
Measure:Efficacy: Overall response rate (ORR)
Time Frame:3 years
Safety Issue:
Description:Overall response rate (ORR), defined as the percentage of participants achieving a CR, mCR, or PR, per IWG criteria.
Measure:Efficacy: Progression free survival (PFS)
Time Frame:3 years
Safety Issue:
Description:Progression free survival (PFS), defined as time from first dose to disease progression, as defined by IWG criteria, or death due to any cause, whichever occurs earlier.
Measure:Efficacy: Overall survival (OS)
Time Frame:3 years
Safety Issue:
Description:Overall survival (OS), defined as time from first dose to death due to any cause.
Measure:Pharmacodynamics (PD): Global methylation (assay) in blood and/or marrow leukemia samples
Time Frame:3 years
Safety Issue:
Measure:Pharmacokinetics (PK): Area under the curve (AUC)
Time Frame:3 years
Safety Issue:
Measure:Pharmacokinetics (PK): Maximum plasma concentration (Cmax)
Time Frame:3 years
Safety Issue:
Measure:Pharmacokinetics (PK): Time to reach maximum concentration (Tmax)
Time Frame:3 years
Safety Issue:
Measure:Pharmacokinetics (PK): Half life (t1/2)
Time Frame:3 years
Safety Issue:


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Alabama at Birmingham

Last Updated

January 28, 2021