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

NCT02841540 | Terminated Phase 1 FDA Drug

• 2 other identifiers: H3B-8800-G000-1012016-001792-70
• Study Type: interventional
• Target: 127
• Locations: 7 countries
• Sites: 49

Brief 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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Dose-limiting Toxicities (DLTs)

  Escalation Cycle 1 (28 days)

• 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.

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

Secondary Outcomes (10)

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

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

• Maximum Observed Plasma Concentration (Cmax)

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

• Time of Maximum Observed Plasma Concentration (Tmax)

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

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

  Up to approximately 50 months

• Number of Participants with Hematologic Improvement

  Up to approximately 50 months

Study Arms (3)

H3B-8800 (RVT-2001) Dose Escalation

EXPERIMENTAL

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

Drug: H3B-8800 (RVT-2001)

H3B-8800 (RVT-2001) MDS Expansion

EXPERIMENTAL

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

Drug: H3B-8800 (RVT-2001)

H3B-8800 (RVT-2001) Dose Optimization

EXPERIMENTAL

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.

Drug: H3B-8800 (RVT-2001)

Interventions

H3B-8800 (RVT-2001) DRUG

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

H3B-8800 (RVT-2001) Dose Escalation; H3B-8800 (RVT-2001) Dose Optimization; H3B-8800 (RVT-2001) MDS Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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 \[HMA\]).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hemavant Sciences GmbH: lead

Study Sites (49)

Arizona Oncology Associates

Tucson, Arizona, 85711, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

City of Hope

Irvine, California, 96218, United States

Location

Rocky Mountain Cancer Center

Aurora, Colorado, 80012, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Oncology Associates of Oregon

Eugene, Oregon, 97401, United States

Location

Texas Oncology

Austin, Texas, 78705, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialist

Fairfax, Virginia, 22301, United States

Location

Algemeen Ziekenhuis Klina

Brasschaat, Belgium

Location

AZ Sint-Jan Brugge Oostende AV

Bruges, Belgium

Location

Universiteit Gent

Ghent, Belgium

Location

University Hospitals Leuven

Leuven, Belgium

Location

Institut Gustave Roussy

Villejuif, Val-de-Marne, 94805, France

Location

CHU Amiens-Picardie

Amiens, France

Location

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

Angers, France

Location

Centre Hospitalier Universitaire (CHU) de Bordeaux

Bordeaux, France

Location

Centre Hospitalier - Le Mans

Le Mans, France

Location

Hôpital Claude Huriez

Lille, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Azienda Ospedaliera Universitaria di Bologna - Policlinico S. Orsola Malpighi

Bologna, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Policlinico Maggiore

Milan, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

Location

IRCCS Istituto Clinico Humanitas Cancer Center

Rozzano, Italy

Location

National Cancer Center

Gyeonggi-do, Goyang-si, South Korea

Location

Daegu Catholic University Medical Center

Daegu, South Korea

Location

Gachon University Gil Medical Center

Incheon, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Hanyang University Seoul Hospital

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

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

Seoul, South Korea

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Valle de Hebrón

Barcelona, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain

Location

Complejo Asistencial Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario y Politécnico La Fe de Valencia

Valencia, Spain

Location

Changhua Christian Hospital

Changhua, Taiwan

Location

Chang-Gung Memorial Hospital, Chiayi

Chiayi City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 40651101 DERIVED

MeSH Terms

Conditions

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

Interventions

H3B-8800

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Keisuke Kuida, MD, PhD

  Hemavant Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: July 22, 2016
• Study Start: October 6, 2016
• Primary Completion: February 13, 2024
• Study Completion: February 13, 2024
• Last Updated: February 14, 2024

Record last verified: 2024-02

Locations

TW (5); US (15); BE (4); KR (8); IT (4); FR (7); ES (6)