Study of REM-422 in Patients With AML or Higher Risk MDS

April 18, 2025 updated by: Remix Therapeutics

A Phase 1, Multicenter, Open-Label Study of REM-422, an MYB mRNA Degrader, in Patients With Relapsed/Refractory AML or Higher-Risk MDS

The goal of this study is to determine the safety and antitumor effects of REM-422, a MYB mRNA degrader, in people with Higher Risk MDS and relapsed/refractory AML

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a Phase 1, open-label, non-randomized, multicenter study investigating REM-422, a potent, selective, and oral small molecule mRNA degrader that reduces expression of the MYB transcription factor for patients with higher risk MDS or relapsed/refractory AML.

This study includes a Dose Escalation Phase and a Dose Expansion Phase. The purpose of the Dose Escalation Phase is to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of REM-422 in patients with higher risk MDS or relapsed/refractory AML. The purpose of Dose Expansion is to further evaluate the safety and anti-tumor activity of the RP2D carried forward from Dose Escalation.

Participation in this study will continue until disease progression, therapy intolerance, or participant withdrawal.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France
        • Recruiting
        • Centre Hospitalier Universitaire (CHU) de Bordeaux
        • Principal Investigator:
          • Arnaud Pigneux, MD
      • Paris, France
        • Recruiting
        • AP-HP - Hôpital Saint-Louis
        • Principal Investigator:
          • Raphael Itzykson, MD
      • Toulouse, France
        • Recruiting
        • IUCT-Oncopole
        • Principal Investigator:
          • Pierre Bories, MD
      • Villejuif, France
        • Recruiting
        • Institut de Cancerologie Gustave-Roussy
        • Principal Investigator:
          • Stephane De Botton, MD
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Principal Investigator:
          • Anthony S Stein, MD
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Onyee Chan, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Amir Fathi, MD
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering
        • Principal Investigator:
          • Eytan M Stein, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Courtney D DiNardo, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Be able to provide informed consent.
  2. Be 18 or older at the time of informed consent.

  3. Disease criteria:

    Histologically confirmed diagnosis of either:

    1. R/R AML, defined as relapse after transplantation, second or later relapse, refractory to initial induction or reinduction treatment or to initial treatment with hypomethylating (HMA)-based combinations, relapse after initial treatment, or otherwise considered relapsed or refractory in the opinion of the Investigator.
    2. High-risk and very-high-risk (VHR) MDS (higher-risk) per the International Prognostic Scoring System-Revised (IPSS-R) and/or International Prognostic Scoring System-Molecular (IPSS-M).
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  5. Has agreed to undergo serial blood and bone marrow sampling.
  6. Participants must have completed systemic non-investigational therapy at least 14 days prior to initiating REM-422. Hydroxyurea is permissible for controlling peripheral leukemic blasts prior to enrollment and for up to 28 days following initiation of REM-422.
  7. Toxicities from prior therapy must be either stable or recovered to ≤ Grade 1.
  8. Participants must be able to swallow and retain oral medications.
  9. Oxygen saturation > 92% on room air or up to 2 L/min supplemental oxygen by nasal cannula with ≤ Grade 1 dyspnea.
  10. People of childbearing potential (POCBP) must have a negative serum beta-human chorionic gonadotropin test result.
  11. POCBP must agree to use acceptable, effective methods of contraception and not donate ova from screening until 6 months after discontinuation of REM-422. Women who have undergone surgical or ablative sterilization or who have been postmenopausal for ≥ 2 years are not considered to be of childbearing potential.
  12. Men must agree to use acceptable, effective methods of contraception and must agree not to donate sperm from the start of receiving REM-422 until 6 months after discontinuation of REM-422.
  13. Adequate organ function and laboratory parameters

Exclusion Criteria:

  1. Active central nervous system (CNS) leukemia or a confirmed diagnosis of CNS leukemia.
  2. Has undergone hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of REM-422 or is receiving immunosuppressive therapy post HSCT at the time of screening, or has GVHD requiring systemic treatment (topical steroids for ongoing skin GVHD is permitted).
  3. Has immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated intravascular coagulation.
  4. Known hypersensitivity or contraindication to any component of REM-422 or to drugs chemically related to REM-422 or its excipients.
  5. Clinically significant active infection. Note: Patients with simple urinary tract infection or uncomplicated bacterial pharyngitis responding to active treatment are permitted. Note: Patients receiving intravenous (IV) antibiotics ≤ 7 days prior to enrollment are excluded (prophylactic antibiotics, antivirals, or antifungals are permitted).
  6. Evidence of active HIV infection.
  7. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  8. Primary immunodeficiency.

  9. Current or expected need for daily systemic corticosteroid therapy ≥ 10 mg of prednisone equivalent.

    Note: Patients who are receiving topical or inhaled corticosteroids with minimal systemic absorption are eligible for enrollment and may continue with minimal corticosteroid use as long as they are on a stable dose.

  10. Live vaccine ≤ 6 weeks prior to the start of REM-422.
  11. Use of strong CYP3A inhibitors (except azole antifungals) or CYP3A inducers
  12. Drugs that reduce gastric acidity, such as H2-receptor antagonists (eg, ranitidine, famotidine) and proton pump inhibitors (eg, omeprazole, esomeprazole) within 7 days prior to the initiation of REM-422 administration or during the study.
  13. Currently pregnant, have intentions to become pregnant during the study duration, or are currently lactating.
  14. Has dysphagia, short-gut syndrome, gastroparesis, or any other condition that limits the ingestion or gastrointestinal absorption of orally administered drugs.
  15. Current use of prohibited medication ≤ 1 week before starting REM-422.
  16. Clinically significant cardiovascular disease:
  17. Has undergone major surgery (opening a mesenchymal barrier such as the pleural cavity, peritoneum, or meninges or surgical procedures requiring general anesthesia) < 4 weeks prior to enrollment.
  18. History of organ transplant that requires use of immunosuppressive agents.
  19. History or current autoimmune disease requiring systemic treatment (eg, Crohn's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus).
  20. Radiation therapy ≤ 7 days prior to the start of REM-422.
  21. Concurrent or previous other malignancy ≤ 2 years of enrollment, except curatively treated malignancies including basal or squamous cell skin cancer, breast cancer, prostate intraepithelial neoplasm, and carcinoma in situ of the cervix.
  22. Receiving any other investigational treatment for any indication ≤ 3 weeks prior to enrollment.
  23. Unwillingness or inability to follow protocol requirements.
  24. Any condition that, in the opinion of the Investigator, would interfere with evaluation of REM-422 or interpretation of the participant's safety or study results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: REM-422

Dose Escalation: Participants will receive escalating doses of REM-422 to determine Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)-422, oral capsule administered once daily

Dose Expansion: Participants will receive REM-422 at the identified RP2D Treatment will continue until disease progression, therapy intolerance, or participant withdrawal Safety evaluation will continue until 30 days of last administration of REM-422
Drug: REM-422

REM-422 is a first in class, small molecule mRNA inhibitor that reduces expression of the MYB transcription factor

REM-422 will be administered orally once daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Frequency and severity of Treatment Emergent Adverse Events (TEAEs)
Time Frame: 24 months
Frequency and severity of Treatment Emergent Adverse Events (TEAEs) will be evaluated according to the NCI-CTCAE version 5.0 and number of participants with Dose Limiting Toxicities will be assessed to determine Safety and Tolerability of REM-422 from the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months.
24 months
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D)
Time Frame: Assessed at the end of Cycle 1 (each cycle is 28 days) for each participant for approximately 24 months
Frequency and severity of Treatment Emergent Adverse Events (TEAEs) will be evaluated according to the NCI-CTCAE version 5.0 and the number of participants with Dose Limiting Toxicities will be assessed from the date of first dose of REM-422 until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months
Assessed at the end of Cycle 1 (each cycle is 28 days) for each participant for approximately 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
AML: Rate of Complete Response (remission) (CR)
Time Frame: 24 months
Rate of Complete Response (CR) will be measured based on Investigator assessment per the modified International Working Group (IWG) response criteria 2003 from the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months.
24 months
AML: Rate of CR with partial hematologic recovery (CRh)
Time Frame: 24 months
Rate of Complete Response (CR) with partial hematologic recovery (CRh) will be measured based on Investigator assessment per the modified International Working Group (IWG) response criteria 2003 from the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months.
24 months
AML: Duration of CR
Time Frame: 24 months
Duration of CR will be evaluated per the modified International Working Group (IWG) response criteria 2003 following treatment with REM-422 from the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months.
24 months
AML: Duration of CRh
Time Frame: 24 months
Duration of CRh will be evaluated per the modified International Working Group (IWG) response criteria 2003 following treatment with REM-422 from the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months.
24 months
AML: Overall response rate (ORR) (CR + CRh + CRi + PR) with incomplete hematologic recovery [CRi] + partial response [PR]) per modified IWG response criteria 2003 based on Investigator assessment
Time Frame: 24 months
Duration of Overall Response Rate (ORR) will be evaluated per the modified International Working Group (IWG) response criteria 2003 following treatment with REM-422 from the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months.
24 months
AML: Duration of response (DOR)
Time Frame: 24 months
Duration of Response (DoR) will be evaluated following treatment with REM-422 based on Investigator assessment for participants who achieve a response per IWG response criteria 2003, defined as the time from when response criteria are first met for CR, CRi, CRh, or PR until progressive disease (PD) per IWG response criteria 2003 is documented or death, whichever occurs first
24 months
MDS: Rate of Compete Response (CR)
Time Frame: 24 months
Rate of CR will be evaluated based on Investigator assessment per IWG 2023 response criteria following treatment with REM-422 for participants who achieve a Complete Response (CR), defined as the time from when criteria are first met for CR until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months.
24 months
MDS: Duration of Complete Response (CR)
Time Frame: 24 months
Duration of CR will be evaluated per IWG 2023 response criteria following treatment with REM-422 based on Investigator assessment for participants who achieve a CR per IWG response criteria 2003, defined as the time from when response criteria are first met for CR until progressive disease (PD) per IWG response criteria 2003 is documented or death, whichever occurs first
24 months
MDS: Overall Response Rate (ORR)
Time Frame: 24 months
ORR will be evaluated per IWG 2023 response criteria based on Investigator assessment following treatment with REM-422 from the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months.
24 months
MDS: Duration of Response (DOR)
Time Frame: 24 months
DOR will be evaluated following treatment with REM-422 based on Investigator assessment for participants who achieve a response per IWG 2023 response criteria, defined as the time from when criteria are first met for CR, CRi, CRh, or PR until PD per IWG 2023 or death, whichever occurs first
24 months
Determine pharmacokinetic profile (Cmax) of REM-422
Time Frame: 24 months
Measure Maximal concentration (Cmax) of REM-422
24 months
Determine pharmacokinetic profile (Cmin) of REM-422
Time Frame: 24 months
Measure Minimal concentration (Cmin) of REM-422
24 months
Determine pharmacokinetic profile (Tmax) of REM-422
Time Frame: 24 months
Measure Time to peak drug concentration (Tmax) of REM-422
24 months
Determine pharmacokinetic profile (AUC) of REM-422
Time Frame: 24 months
Measure Area Under the Curve (AUC) of REM-422
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Remix Therapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Christopher Bowden, MD, Remix Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 26, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 15, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 15, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 23, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 29, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 7, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 23, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • REM-422-102

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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