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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02841540
Other study ID # H3B-8800-G000-101
Secondary ID 2016-001792-70
Status Terminated
Phase Phase 1
First received
Last updated
Start date October 6, 2016
Est. completion date February 13, 2024

Study information

Verified date February 2024
Source Hemavant Sciences GmbH
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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


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.


Recruitment information / eligibility

Status Terminated
Enrollment 127
Est. completion date February 13, 2024
Est. primary completion date February 13, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Belgium Algemeen Ziekenhuis Klina Brasschaat
Belgium AZ Sint-Jan Brugge Oostende AV Brugge
Belgium Universiteit Gent Gent
Belgium University Hospitals Leuven Leuven
France CHU Amiens-Picardie Amiens
France Centre Hospitalier Universitaire d'Angers (CHU d'Angers) Angers
France Centre Hospitalier Universitaire (CHU) de Bordeaux Bordeaux
France Centre Hospitalier - Le Mans Le Mans
France Hôpital Claude Huriez Lille
France Centre Hospitalier Lyon Sud Pierre-Bénite
France Institut Gustave Roussy Villejuif Val-de-Marne
Italy Azienda Ospedaliera Universitaria di Bologna - Policlinico S. Orsola Malpighi Bologna
Italy Fondazione IRCCS Cà Granda Ospedale Policlinico Maggiore Milano
Italy Fondazione IRCCS Policlinico San Matteo Pavia
Italy IRCCS Istituto Clinico Humanitas Cancer Center Rozzano
Korea, Republic of Daegu Catholic University Medical Center Daegu
Korea, Republic of National Cancer Center Gyeonggi-do Goyang-si
Korea, Republic of Gachon University Gil Medical Center Incheon
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Hanyang University Seoul Hospital Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of The Catholic University of Korea Seoul St. Mary's Hospital Seoul
Spain Hospital Universitario Valle de Hebrón Barcelona
Spain Hospital General Universitario Gregorio Marañon Madrid
Spain Hospital Universitario Fundación Jiménez Díaz Madrid
Spain Clinica Universidad de Navarra Pamplona Navarra
Spain Complejo Asistencial Universitario de Salamanca Salamanca
Spain Hospital Universitario y Politécnico La Fe de Valencia Valencia
Taiwan Changhua Christian Hospital Changhua
Taiwan Chang-Gung Memorial Hospital, Chiayi Chiayi City
Taiwan China Medical University Hospital Taichung
Taiwan National Cheng Kung University Hospital Tainan
Taiwan National Taiwan University Hospital Taipei
United States Rocky Mountain Cancer Center Aurora Colorado
United States Texas Oncology Austin Texas
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Dana Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States Karmanos Cancer Institute Detroit Michigan
United States City of Hope Duarte California
United States Oncology Associates of Oregon Eugene Oregon
United States Virginia Cancer Specialist Fairfax Virginia
United States MD Anderson Cancer Center Houston Texas
United States City of Hope Irvine California
United States Mayo Clinic Jacksonville Jacksonville Florida
United States University of Miami Miami Florida
United States Mayo Clinic Rochester Minnesota
United States Arizona Oncology Associates Tucson Arizona

Sponsors (1)

Lead Sponsor Collaborator
Hemavant Sciences GmbH

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants with Dose-limiting Toxicities (DLTs) Escalation Cycle 1 (28 days)
Primary 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 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 Up to Cycle 6 Day 15 (each cycle length=28 days)
Secondary Maximum Observed Plasma Concentration (Cmax) Plasma samples for PK analyses will be collected at predetermined timepoint and analyzed Up to Cycle 6 Day 15 (each cycle length=28 days)
Secondary Time of Maximum Observed Plasma Concentration (Tmax) Plasma samples for PK analyses will be collected at predetermined timepoint and analyzed Up to Cycle 6 Day 15 (each cycle length=28 days)
Secondary Number of Participants who Achieve Red Blood Cell (RBC) Transfusion Independence Up to approximately 50 months
Secondary Number of Participants with Hematologic Improvement Up to approximately 50 months
Secondary 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. Up to approximately 50 months
Secondary 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. Up to approximately 50 months
Secondary Time to Progression Up to approximately 50 months
Secondary Overall Survival (OS) Overall Survival is defined as the time from first dose date to the date of death from any cause. Up to approximately 50 months
Secondary Mortality Rate at 3 and 6 Months Months 3 and 6
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