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A Phase 1 Study to Evaluate H3B-8800 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 : February 22, 2019
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Eisai Inc. ( H3 Biomedicine Inc. )

Brief Summary:
This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of H3B-8800 in participants with Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML), or Chronic Myelomonocytic Leukemia (CMML). The study consists of two parts, a dose escalation part (Part 1) and an expansion part (Part 2) exploring a multiple once daily (QD) schedules at the recommended phase 2 dose (RP2D).

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

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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: Basic Science
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 : December 1, 2019
Estimated Study Completion Date : December 1, 2019


Arm Intervention/treatment
Experimental: H3B-8800 (escalation and expansion)
H3B-8800 Acute Myeloid Leukemia or High Risk Myelodysplastic Syndromes/ Low Risk Myelodysplastic Syndromes/ Chronic Myelomonocytic Leukemia.
Drug: H3B-8800
H3B-8800 by mouth once daily at specified doses.




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: Escalation and Expansion continuously throughout the study until 30 days after treatment discontinuation (up to 38 months) ]

Secondary Outcome Measures :
  1. Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) [ Time Frame: Days 1, 4 and/or 15 of Cycle 1 (28 days) at pre-dose and at multiple time points (up to 24 hours) post-dose ]
  2. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Days 1, 4 and/or 15 of Cycle 1 (28 days) at pre-dose and at multiple time points (up to 24 hours) post-dose ]
  3. Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Days 1, 4 and/or 15 of Cycle 1 (28 days) at pre-dose and at multiple time points (up to 24 hours) post-dose ]
  4. Objective Response Rate (ORR) [ Time Frame: Up to approximately 38 months ]
  5. Duration of Response (DOR) [ Time Frame: Up to approximately 38 months ]
  6. Number of Participants with Hematologic Improvement [ Time Frame: Up to approximately 38 months ]
  7. Percentage of Participants who Achieve Red Blood Cell (RBC) Transfusion Independence [ Time Frame: Up to approximately 38 months ]
  8. Time to Progression [ Time Frame: Up to approximately 38 months ]
  9. Overall Survival (OS) [ Time Frame: Up to approximately 38 months ]
  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.
  2. The participant 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. Participants with lower-risk MDS/CMML must be transfusion-dependent for red blood cells or platelets (as determined by instructional practices or local standard of care). Participants who are red blood cell transfusion-dependent must also have failed erythropoiesis stimulating agents (ESA) (primary resistance or relapse after a response) or have serum EPO levels > 500 U/L. These lower-risk participants must have platelet counts above 50,000 mm^3 in the absence of transfusion for 8 weeks.

    C. Participants with AML must either refuse or not be considered candidates for intensive induction chemotherapy using consensus criteria for defining such participants. Previously treated participants should have evidence of persistent or recurrent AML in the peripheral blood and/or bone marrow that is refractory to, or has relapsed from, their most recent prior line of treatment. For AML, participants must have WBC < 15 × 10^9/L.

    D. 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. Adequate baseline organ function

Exclusion Criteria:

  1. Diagnosis of a core binding factor leukemia (t(8;21), t(16;16) or inv(16)).
  2. Participant is candidate for hematopoietic stem cell transplants at the time of enrollment.
  3. Family history of Leber Hereditary Optic Neuropathy, Autosomal Dominant Optic Atrophy, Late-Onset Retinal Degeneration, Familial Dysautonomia or other hereditary mitochondrial disease, unless the causative mutation(s) in the family have been determined and the participant has tested negative for the mutation(s).
  4. Known prior or current retinal or optic nerve disease (example, Retinitis Pigmentosa, diabetic retinopathy, optic neuritis) based on screening ophthalmology assessment for eligibility.
  5. Corrected vision is worse than 20/40 unless due to cataracts.
  6. Vitamin B12, folate or vitamin A deficiency. Rescreening following repletion therapy is acceptable.

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: Eisai Medical Information 1-888-274-2378 esi_oncmedinfo@eisai.com

  Show 27 Study Locations
Sponsors and Collaborators
H3 Biomedicine Inc.
Eisai Inc.

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Responsible Party: H3 Biomedicine Inc.
ClinicalTrials.gov Identifier: NCT02841540     History of Changes
Other Study ID Numbers: H3B-8800-G000-101
2016-001792-70 ( EudraCT Number )
First Posted: July 22, 2016    Key Record Dates
Last Update Posted: February 22, 2019
Last Verified: August 2018

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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 Eisai Inc. ( H3 Biomedicine Inc. ):
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
H3B-8800
Splicing Modulator
CMML
AML
MDS

Additional relevant MeSH terms:
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Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases