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NTX-301 in MDS/AML

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04167917
Recruitment Status : Recruiting
First Posted : November 19, 2019
Last Update Posted : December 7, 2021
Information provided by (Responsible Party):
Pankit Vachhani, University of Alabama at Birmingham

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia Drug: NTX-301 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of NTX-301, an Oral DNMT1 Inhibitor, in Patients With MDS and AML
Actual Study Start Date : January 6, 2021
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : March 31, 2025

Arm Intervention/treatment
Experimental: NTX-301 Drug: NTX-301
oral hypomethylating agent

Primary Outcome Measures :
  1. Safety/tolerability: Incidence of treatment related adverse events (AEs) and dose-limiting toxicities (DLTs) [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Efficacy: Clinical Benefit Rate (CBR) [ Time Frame: 3 years ]
    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.

  2. Efficacy: Overall response rate (ORR) [ Time Frame: 3 years ]
    Overall response rate (ORR), defined as the percentage of participants achieving a CR, mCR, or PR, per IWG criteria.

  3. Efficacy: Progression free survival (PFS) [ Time Frame: 3 years ]
    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.

  4. Efficacy: Overall survival (OS) [ Time Frame: 3 years ]
    Overall survival (OS), defined as time from first dose to death due to any cause.

  5. Pharmacodynamics (PD): Global methylation (assay) in blood and/or marrow leukemia samples [ Time Frame: 3 years ]
  6. Pharmacokinetics (PK): Area under the curve (AUC) [ Time Frame: 3 years ]
  7. Pharmacokinetics (PK): Maximum plasma concentration (Cmax) [ Time Frame: 3 years ]
  8. Pharmacokinetics (PK): Time to reach maximum concentration (Tmax) [ Time Frame: 3 years ]
  9. Pharmacokinetics (PK): Half life (t1/2) [ Time Frame: 3 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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 procedure.
  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) Cardiac:
    • 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 permitted
    • no signs or symptoms of acute graft versus host disease, other than Grade 1 skin involvement.
    • 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 absorption.
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04167917

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Contact: Pankit Vachhani, MD 205-975-7850
Contact: Pam Hardwick, RN, OCN, CCRP 205-975-5387

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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Pankit Vachhani, MD    205-975-7850   
Contact: Pam Hardwick, RN, OCN    205-975-5387   
Sponsors and Collaborators
University of Alabama at Birmingham
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Responsible Party: Pankit Vachhani, Asst Prof of Medicine, University of Alabama at Birmingham Identifier: NCT04167917    
Other Study ID Numbers: UAB-NTX301
First Posted: November 19, 2019    Key Record Dates
Last Update Posted: December 7, 2021
Last Verified: December 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases