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Leukemia, Myeloid, AcutePhase 1Encore-MDSNCT02841540

A Study of H3B-8800 (RVT-2001) in Participants With Lower Risk Myelodysplastic Syndromes

A Phase 1 study testing H3B-8800 (RVT-2001) in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Hemavant Sciences GmbH at 49 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

A Phase 1, an Open-label, Multicenter Phase 1 Trial to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Splicing Modulator H3B-8800 (RVT-2001) for Subjects With Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
H3B-8800 (RVT-2001)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
127 participants
Where
49 sitesin 7 countries
Study dates
6 Oct 2016to 13 Feb 2024
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Confirmed diagnosis of MDS, CMML, or AML.
  • For the MDS Expansion cohort, participants must be lower-risk MDS, defined as low or intermediate-1 risk categorization per International Prognostic Scoring System (IPSS) criteria that carries a missense SF3B1 mutation.
  • For the Dose Optimization cohort, participants must be transfusion-dependent, lower-risk MDS, defined as very-low to intermediate risk categorization per IPSS-R criteria that carries a missense SF3B1 mutation.
  • Participants must meet the following criteria relevant to their specific diagnosis:
  • Participants with higher-risk MDS/CMML must be intolerant of hypomethylating agents (HMAs) or not have responded to 4 treatment cycles of decitabine or 6 treatment cycles of azacitidine, or must have progressed at any point after initiation of an HMA.
  • For the Dose Escalation portion, participants with lower-risk MDS/CMML must be transfusion-dependent for red blood cells or platelets.
Show all 15Show fewer
  • For the MDS expansion cohort, lower risk MDS participants must be RBC transfusion dependent according to IWG 2006 criteria and must also have failed erythropoiesis stimulating agents (ESA) or have serum erythropoietin (EPO) levels greater than (>) 500 units per liter (U/L).
  • For the Dose Optimization cohort, lower-risk MDS participants must be RBC transfusion-dependent at baseline defined as ≥3 RBC units (concentrates) in 16-weeks in at least 2 transfusion episodes prior to the first dose of H3B-8800 (RVT-2001) and must also have failed ESA or have serum EPO levels > 500 U/L. Any ESA use should be discontinued ≥6 weeks prior to enrollment.
  • Participants with AML must either refuse or not be considered candidates for intensive induction chemotherapy using consensus criteria for defining such participants.
  • Participants with CMML must have been treated with at least one prior therapy (hydroxyurea or a hypomethylating agent [HMA]).
  • Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
  • For MDS expansion and Dose optimization cohorts - absolute neutrophil count (ANC) greater than or equal to (>=) 500/ microliter (mcL) (0.5*10^9/L).
  • For expansion and Dose optimization cohorts- platelet count >50,000/mcL (50*10^9/L).
  • For Dose-optimization cohort: No prior HMA or lenalidomide in participants with lower-risk MDS.
  • Adequate baseline organ function.

Who cannot join

  • Diagnosis of a core binding factor leukemia (t(8;21), t(16;16) or inv(16)). Diagnosis of acute promyelocytic leukemia (t(15;17))
  • Participants are deemed candidate for hematopoietic stem cell transplants at the time of enrollment (for AML participants only).
  • Known prior or current retinal or optic nerve disease (example, Retinitis Pigmentosa, diabetic retinopathy, optic neuritis) not stable for at least 6 months.
  • History of clinically significant, uncorrected vitamin B12 or folate deficiency.

Trial locations and contacts

49 sites in 7 countries.

49 sites in 7 countries

United States15 sites

  • Rocky Mountain Cancer Center

    Aurora, Colorado, 80012

  • Texas Oncology

    Austin, Texas, 78705

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope

    Duarte, California, 91010

  • Oncology Associates of Oregon

    Eugene, Oregon, 97401

  • Virginia Cancer Specialist

    Fairfax, Virginia, 22301

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • City of Hope

    Irvine, California, 96218

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • University of Miami

    Miami, Florida, 33136

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Arizona Oncology Associates

    Tucson, Arizona, 85711

Other trials in United States

South Korea8 sites

  • Daegu Catholic University Medical Center

    Daegu

  • National Cancer Center

    Gyeonggi-do, Goyang-si

  • Gachon University Gil Medical Center

    Incheon

  • Asan Medical Center

    Seoul

  • Hanyang University Seoul Hospital

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • The Catholic University of Korea Seoul St. Mary's Hospital

    Seoul

Other trials in South Korea

France7 sites

  • CHU Amiens-Picardie

    Amiens

  • Centre Hospitalier Universitaire d'Angers (CHU d'Angers)

    Angers

  • Centre Hospitalier Universitaire (CHU) de Bordeaux

    Bordeaux

  • Centre Hospitalier - Le Mans

    Le Mans

  • Hôpital Claude Huriez

    Lille

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite

  • Institut Gustave Roussy

    Villejuif, Val-de-Marne, 94805

Other trials in France

Spain6 sites

  • Hospital Universitario Valle de Hebrón

    Barcelona

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Complejo Asistencial Universitario de Salamanca

    Salamanca

  • Hospital Universitario y Politécnico La Fe de Valencia

    Valencia

Other trials in Spain

Taiwan5 sites

  • Changhua Christian Hospital

    Changhua

  • Chang-Gung Memorial Hospital, Chiayi

    Chiayi City

  • China Medical University Hospital

    Taichung

  • National Cheng Kung University Hospital

    Tainan

  • National Taiwan University Hospital

    Taipei

Other trials in Taiwan

Belgium4 sites

  • Algemeen Ziekenhuis Klina

    Brasschaat

  • AZ Sint-Jan Brugge Oostende AV

    Bruges

  • Universiteit Gent

    Ghent

  • University Hospitals Leuven

    Leuven

Other trials in Belgium

Italy4 sites

  • Azienda Ospedaliera Universitaria di Bologna - Policlinico S. Orsola Malpighi

    Bologna

  • Fondazione IRCCS Cà Granda Ospedale Policlinico Maggiore

    Milan

  • Fondazione IRCCS Policlinico San Matteo

    Pavia

  • IRCCS Istituto Clinico Humanitas Cancer Center

    Rozzano

Other trials in Italy

About this study

Official title: An Open-label, Multicenter Phase 1 Trial to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Splicing Modulator H3B-8800 for Subjects With Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia

A Phase 1, an Open-label, Multicenter Phase 1 Trial to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Splicing Modulator H3B-8800 (RVT-2001) for Subjects With Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia

Read the detailed description

This study is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of H3B-8800 (RVT-2001) in subset of participants with Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML), or Chronic Myelomonocytic Leukemia (CMML). The study consists of three parts, the dose escalation part (Part 1) exploring multiple once daily (QD) schedules and MDS Expansion part (Part 2) and Dose Optimization part (Part 3) exploring dosing schedules in lower-risk MDS.

Being tested
H3B-8800 (RVT-2001)
Keywords
Myelodysplastic Syndromes, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, H3B-8800 (RVT-2001), Splicing Modulator, CMML, AML, MDS
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

What participants receive

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

  • H3B-8800 (RVT-2001)Drug

    H3B-8800 (RVT-2001) orally at specified doses and schedules.

Study groups in NCT02841540
Study groupRoleWhat they receive
H3B-8800 (RVT-2001) Dose EscalationExperimentalH3B-8800 Acute Myeloid Leukemia or High Risk Myelodysplastic Syndromes/ Low Risk Myelodysplastic Syndromes/ Chronic Myelomonocytic Leukemia.
Receives: Drug: H3B-8800 (RVT-2001)
H3B-8800 (RVT-2001) MDS ExpansionExperimentalTransfusion-dependent, lower-risk MDS subjects (very-low to intermediate risk categorization per IPSS-R) with missense mutations in SF3B1.
Receives: Drug: H3B-8800 (RVT-2001)
H3B-8800 (RVT-2001) Dose OptimizationExperimentalTransfusion-dependent, lower-risk MDS subjects (very-low to intermediate risk categorization per IPSS-R) with missense mutations in SF3B1, and who have not been exposed to HMA's or lenalidomide in a prior line of therapy.
Receives: Drug: H3B-8800 (RVT-2001)

What is being measured

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

  1. Number of Participants with Dose-limiting Toxicities (DLTs)

    Measured: Escalation Cycle 1 (28 days)

  2. Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    The type and frequency of AEs and SAEs using CTCAE v4.03, as well as changes in clinical laboratory values, ECG parameters, ophthalmologic examinations, and vital sign measurements.

    Measured: From the first dose of study drug until 30 days after final dose of study drug (up to approximately 50 months)

Secondary outcomes (10)

  1. Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t)

    Plasma samples for PK analyses will be collected at predetermined timepoint and analyzed

    Measured: Up to Cycle 6 Day 15 (each cycle length=28 days)

  2. Maximum Observed Plasma Concentration (Cmax)

    Plasma samples for PK analyses will be collected at predetermined timepoint and analyzed

    Measured: Up to Cycle 6 Day 15 (each cycle length=28 days)

  3. Time of Maximum Observed Plasma Concentration (Tmax)

    Plasma samples for PK analyses will be collected at predetermined timepoint and analyzed

    Measured: Up to Cycle 6 Day 15 (each cycle length=28 days)

  4. Number of Participants who Achieve Red Blood Cell (RBC) Transfusion Independence

    Measured: Up to approximately 50 months

  5. Number of Participants with Hematologic Improvement

    Measured: Up to approximately 50 months

  6. Objective Response Rate (ORR)

    ORR will be defined as the percentage of participants achieving a best overall response of partial remission (PR) or complete remission (CR) (PR + CR), from first dose date until disease progression/recurrence. CR includes CR with incomplete blood count recovery (CRi) in AML participants and marrow CR in MDS participants and optimal marrow response in CMML participants. Response will be assessed by the Investigator and the independent central review based on 2006 International Working Group (IWG) response criteria for MDS, 2003 IWG criteria for AML, and the international consortium proposal of uniform response criteria for CMML published in 2015.

    Measured: Up to approximately 50 months

  7. Duration of Response (DOR)

    DOR will be defined as the time from the date of first documented CR/PR until the first documentation of confirmed relapse, or death, whichever comes first.

    Measured: Up to approximately 50 months

  8. Time to Progression

    Measured: Up to approximately 50 months

  9. Overall Survival (OS)

    Overall Survival is defined as the time from first dose date to the date of death from any cause.

    Measured: Up to approximately 50 months

  10. Mortality Rate at 3 and 6 Months

    Measured: Months 3 and 6

Timeline

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

  1. First posted22 Jul 2016 (estimated)
  2. Study start6 Oct 2016
  3. Primary completion13 Feb 2024
  4. Study completion13 Feb 2024

Why it stopped: The study was terminated after conducting an interim analysis of the available data where it became evident that the observed efficacy results were not in alignment with the initially set expectations.

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
127 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02841540
Sponsor's protocol ID
H3B-8800-G000-101
Other IDs
2016-001792-70, 2016
Acronym
Encore-MDS
Status last verified
Feb 2024
First submitted
20 Jul 2016
Last updated
14 Feb 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Maron MI, Abdel-Wahab O. Outstanding Questions to Understand and Target Splicing Factor-Mutant Blood Cancers. Blood Cancer Discov. 2026 May 5;7(3):348-352. doi: 10.1158/2643-3230.BCD-26-0047.

    PubMed 42013378

  • Foran JM, Sanz GF, Watts JM, Brunner AM, Fossard G, Della Porta MG, Tsai XC, Garcia-Manero G, Dimicoli-Salazar S, Fletcher L, Kim YJ, Font P, Alfonso-Pierola A, Alonso-Dominguez JM, Benton C, Hong J, Malcovati L, Mazure D, Lee JH, Yeh SP, Goursaud L, Barcellini W, Wu E, Corzo D, Kuida K, Stone RM. Phase 1 first-in-human dose-expansion study of the oral SF3B1 modulator H3B-8800 in lower-risk myelodysplastic syndrome. Leuk Res. 2025 Sep;156:107735. doi: 10.1016/j.leukres.2025.107735. Epub 2025 Jun 9.

    PubMed 40651101

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing H3B-8800 (RVT-2001) in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Hemavant Sciences GmbH at 49 sites in 7 countries.

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 15 inclusion and 4 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: stopped early, as of the sponsor's last update on 14 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, South Korea, France, Spain, Taiwan and 2 more countries. 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 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.

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

Are results available for this study?

The study was stopped early (reason given: The study was terminated after conducting an interim analysis of the available data where it became evident that the observed efficacy results were not in alignment with the initially set expectations.). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with Dose-limiting Toxicities (DLTs) (time frame: Escalation Cycle 1 (28 days)). The study lists 2 primary outcomes in all. 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 NCT02841540, which also lists 2 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 14 Feb 2024.

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