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

NCT ID: NCT02841540

Last Updated: 2024-02-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-06

Study Completion Date

2024-02-13

Brief Summary

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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

Detailed Description

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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.

Conditions

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Leukemia, Myeloid, Acute Myelodysplastic Syndromes Leukemia, Myelomonocytic, Chronic

Keywords

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Myelodysplastic Syndromes Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia H3B-8800 (RVT-2001) Splicing Modulator CMML AML MDS

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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H3B-8800 (RVT-2001) Dose Escalation

H3B-8800 Acute Myeloid Leukemia or High Risk Myelodysplastic Syndromes/ Low Risk Myelodysplastic Syndromes/ Chronic Myelomonocytic Leukemia.

Group Type EXPERIMENTAL

H3B-8800 (RVT-2001)

Intervention Type DRUG

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

H3B-8800 (RVT-2001) MDS Expansion

Transfusion-dependent, lower-risk MDS subjects (very-low to intermediate risk categorization per IPSS-R) with missense mutations in SF3B1.

Group Type EXPERIMENTAL

H3B-8800 (RVT-2001)

Intervention Type DRUG

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

H3B-8800 (RVT-2001) Dose Optimization

Transfusion-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.

Group Type EXPERIMENTAL

H3B-8800 (RVT-2001)

Intervention Type DRUG

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

Interventions

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H3B-8800 (RVT-2001)

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. Participants must meet the following criteria relevant to their specific diagnosis:

A. 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.

B. For the Dose Escalation portion, participants with lower-risk MDS/CMML must be transfusion-dependent for red blood cells or platelets.

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).

C. 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.

D. Participants with AML must either refuse or not be considered candidates for intensive induction chemotherapy using consensus criteria for defining such participants.

E. Participants with CMML must have been treated with at least one prior therapy (hydroxyurea or a hypomethylating agent \[HMA\]).
3. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
4. For MDS expansion and Dose optimization cohorts - absolute neutrophil count (ANC) greater than or equal to (\>=) 500/ microliter (mcL) (0.5\*10\^9/L).
5. For expansion and Dose optimization cohorts- platelet count \>50,000/mcL (50\*10\^9/L).
6. For Dose-optimization cohort: No prior HMA or lenalidomide in participants with lower-risk MDS.
7. Adequate baseline organ function.

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hemavant Sciences GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Keisuke Kuida, MD, PhD

Role: STUDY_DIRECTOR

Hemavant Sciences

Locations

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Arizona Oncology Associates

Tucson, Arizona, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

City of Hope

Irvine, California, United States

Site Status

Rocky Mountain Cancer Center

Aurora, Colorado, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Oncology Associates of Oregon

Eugene, Oregon, United States

Site Status

Texas Oncology

Austin, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Virginia Cancer Specialist

Fairfax, Virginia, United States

Site Status

Algemeen Ziekenhuis Klina

Brasschaat, , Belgium

Site Status

AZ Sint-Jan Brugge Oostende AV

Bruges, , Belgium

Site Status

Universiteit Gent

Ghent, , Belgium

Site Status

University Hospitals Leuven

Leuven, , Belgium

Site Status

Institut Gustave Roussy

Villejuif, Val-de-Marne, France

Site Status

CHU Amiens-Picardie

Amiens, , France

Site Status

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

Angers, , France

Site Status

Centre Hospitalier Universitaire (CHU) de Bordeaux

Bordeaux, , France

Site Status

Centre Hospitalier - Le Mans

Le Mans, , France

Site Status

Hôpital Claude Huriez

Lille, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Azienda Ospedaliera Universitaria di Bologna - Policlinico S. Orsola Malpighi

Bologna, , Italy

Site Status

Fondazione IRCCS Cà Granda Ospedale Policlinico Maggiore

Milan, , Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

IRCCS Istituto Clinico Humanitas Cancer Center

Rozzano, , Italy

Site Status

National Cancer Center

Gyeonggi-do, Goyang-si, South Korea

Site Status

Daegu Catholic University Medical Center

Daegu, , South Korea

Site Status

Gachon University Gil Medical Center

Incheon, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Hanyang University Seoul Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

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

Seoul, , South Korea

Site Status

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status

Hospital Universitario Valle de Hebrón

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Site Status

Complejo Asistencial Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario y Politécnico La Fe de Valencia

Valencia, , Spain

Site Status

Changhua Christian Hospital

Changhua, , Taiwan

Site Status

Chang-Gung Memorial Hospital, Chiayi

Chiayi City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Countries

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Germany United States Belgium France Italy South Korea Spain Taiwan

References

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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.

Reference Type DERIVED
PMID: 40651101 (View on PubMed)

Other Identifiers

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2016-001792-70

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

H3B-8800-G000-101

Identifier Type: -

Identifier Source: org_study_id