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A Phase 1 Study to Evaluate H3B-8800 in Participants With Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia

NCT02841540

Description:

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).

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study to Evaluate H3B-8800 in Participants With Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia
  • 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

Clinical Trial IDs

  • ORG STUDY ID: H3B-8800-G000-101
  • SECONDARY ID: 2016-001792-70
  • NCT ID: NCT02841540

Conditions

  • Myelodysplastic Syndromes
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia

Interventions

DrugSynonymsArms
H3B-8800H3B-8800 (escalation and expansion)

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
H3B-8800 (escalation and expansion)ExperimentalH3B-8800 Acute Myeloid Leukemia or High Risk Myelodysplastic Syndromes/ Low Risk Myelodysplastic Syndromes/ Chronic Myelomonocytic Leukemia.
  • H3B-8800

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame:Escalation Cycle 1 (28 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 38 months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:Up to approximately 38 months
Safety Issue:
Description:
Measure:Number of Participants with Hematologic Improvement
Time Frame:Up to approximately 38 months
Safety Issue:
Description:
Measure:Percentage of Participants who Achieve Red Blood Cell (RBC) Transfusion Independence
Time Frame:Up to approximately 38 months
Safety Issue:
Description:
Measure:Time to Progression
Time Frame:Up to approximately 38 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Up to approximately 38 months
Safety Issue:
Description:
Measure:Mortality Rate at 3 and 6 Months
Time Frame:Months 3 and 6
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H3 Biomedicine Inc.

Trial Keywords

  • Myelodysplastic Syndromes
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • H3B-8800
  • Splicing Modulator
  • CMML
  • AML
  • MDS

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