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Trial record 1 of 1 for:    NCT02841540
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A Study of H3B-8800 (RVT-2001) in Participants With Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia

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ClinicalTrials.gov Identifier: NCT02841540
Recruitment Status : Recruiting
First Posted : July 22, 2016
Last Update Posted : October 25, 2022
Sponsor:
Information provided by (Responsible Party):
Hemavant Sciences GmbH

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

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Myelodysplastic Syndromes Leukemia, Myelomonocytic, Chronic Drug: H3B-8800 (RVT-2001) Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 6, 2016
Estimated Primary Completion Date : September 1, 2024
Estimated Study Completion Date : December 1, 2024


Arm Intervention/treatment
Experimental: H3B-8800 (RVT-2001) Dose Escalation
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) orally at specified doses and schedules.

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

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




Primary Outcome Measures :
  1. Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: Escalation Cycle 1 (28 days) ]
  2. Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From the first dose of study drug until 30 days after final dose of study drug (up to approximately 50 months) ]
    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.


Secondary Outcome Measures :
  1. Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) [ Time Frame: Up to Cycle 6 Day 15 (each cycle length=28 days) ]
    Plasma samples for PK analyses will be collected at predetermined timepoint and analyzed

  2. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to Cycle 6 Day 15 (each cycle length=28 days) ]
    Plasma samples for PK analyses will be collected at predetermined timepoint and analyzed

  3. Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Up to Cycle 6 Day 15 (each cycle length=28 days) ]
    Plasma samples for PK analyses will be collected at predetermined timepoint and analyzed

  4. Number of Participants who Achieve Red Blood Cell (RBC) Transfusion Independence [ Time Frame: Up to approximately 50 months ]
  5. Number of Participants with Hematologic Improvement [ Time Frame: Up to approximately 50 months ]
  6. Objective Response Rate (ORR) [ Time Frame: Up to approximately 50 months ]
    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.

  7. Duration of Response (DOR) [ Time Frame: Up to approximately 50 months ]
    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.

  8. Time to Progression [ Time Frame: Up to approximately 50 months ]
  9. Overall Survival (OS) [ Time Frame: Up to approximately 50 months ]
    Overall Survival is defined as the time from first dose date to the date of death from any cause.

  10. Mortality Rate at 3 and 6 Months [ Time Frame: Months 3 and 6 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02841540


Contacts
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Contact: Hemavant Sciences Clinical Contact (213) 549-2979 hemavant@patientwing.com

Locations
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Sponsors and Collaborators
Hemavant Sciences GmbH
Investigators
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Study Director: Keisuke Kuida, MD, PhD Hemavant Sciences
Additional Information:
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Responsible Party: Hemavant Sciences GmbH
ClinicalTrials.gov Identifier: NCT02841540    
Other Study ID Numbers: H3B-8800-G000-101
2016-001792-70 ( EudraCT Number )
First Posted: July 22, 2016    Key Record Dates
Last Update Posted: October 25, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hemavant Sciences GmbH:
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
H3B-8800 (RVT-2001)
Splicing Modulator
CMML
AML
MDS
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases