Clinical Trial - NCT02841540

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

Recruiting

Sponsor: H3 Biomedicine Inc.

Collaborators: Eisai Inc.

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02841540

Protocol Info

Short Description: SPLICING MODULATOR H3B-8800 IN MDS, AML, CML
Long Description: 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
MGH Status: Open
Sponsor: H3 Biomedicine Inc.
Disease Program: Leukemia

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




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).
Condition Title Intervention Phase
Myelodysplastic Syndromes Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia H3B-8800 Phase 1
Study Type Interventional
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

Primary Outcome Measures

Number of Participants with Dose-limiting Toxicities (DLTs) [Time Frame: Escalation Cycle 1 (28 days)] [Designated as safety issue: ]

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)] [Designated as safety issue: ]


Secondary Outcome Measures

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Objective Response Rate (ORR) [Time Frame: Up to approximately 38 months] [Designated as safety issue: ]

Duration of Response (DOR) [Time Frame: Up to approximately 38 months] [Designated as safety issue: ]

Number of Participants with Hematologic Improvement [Time Frame: Up to approximately 38 months] [Designated as safety issue: ]

Percentage of Participants who Achieve Red Blood Cell (RBC) Transfusion Independence [Time Frame: Up to approximately 38 months] [Designated as safety issue: ]

Time to Progression [Time Frame: Up to approximately 38 months] [Designated as safety issue: ]

Overall Survival (OS) [Time Frame: Up to approximately 38 months] [Designated as safety issue: ]

Mortality Rate at 3 and 6 Months [Time Frame: Months 3 and 6] [Designated as safety issue: ]

Estimated Enrollment: 200
Study Start Date: October 2016
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019
Arms Assigned Interventions

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.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02841540

Locations

  • United States, California
    • Stanford Cancer Center Stanford, California, United States, 94305
  • United States, Colorado
    • SCRI - Colorado Blood Cancer Institute Denver, Colorado, United States, 80218
  • United States, Florida
    • Mayo Clinic Jacksonville Jacksonville, Florida, United States, 32224
    • University of Miami Miami, Florida, United States, 33136
    • H Lee Moffitt Cancer Center and Research Institute Tampa, Florida, United States, 33612
  • United States, Illinois
    • University of Chicago Chicago, Illinois, United States, 60637
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02115
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • Karmanos Cancer Institute Detroit, Michigan, United States, 48201
  • United States, Minnesota
    • Mayo Clinic Rochester, Minnesota, United States, 55905
  • United States, New York
    • Rosewell Park Cancer Center Buffalo, New York, United States, 14263
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, North Carolina
    • University of North Carolina Chapel Hill Chapel Hill, North Carolina, United States, 27514
  • United States, Ohio
    • Cleveland Clinic Cleveland, Ohio, United States, 21287
  • United States, Tennessee
    • SCRI - Tennessee Oncology Nashville, Tennessee, United States, 37203
  • United States, Texas
    • MD Anderson Cancer Center Houston, Texas, United States, 77030
  • United States, Washington
    • Fred Hutchinson Cancer Research Center Seattle, Washington, United States, 98109
  • France, Val-de-Marne
    • Institut Gustave Roussy Villejuif, Val-de-Marne, France, 94805
  • France,
    • Hôpital Saint Louis Paris, , France, 75475
  • Germany, Lower Saxony
    • Eisai Trial Site 1 Hannover, Lower Saxony, Germany, 30625
  • Germany, Sachsen
    • Eisai Trial Site 2 Dresden, Sachsen, Germany, 1307
    • Eisai Trial Site 3 Leipzig, Sachsen, Germany, 1403
  • Spain, Navarra
    • Clinica Universidad Navarra Pamplona, Navarra, Spain, 31008
  • Spain,
    • Hospital General Universitario Gregorio Marañon Madrid, , Spain, 28007
    • Hospital Universitario Fundacion Jimenez Diaz Madrid, , Spain, 28040
    • Hospital Universitario HM Sanchinarro - CIOCC Madrid, , Spain, 28050

Sponsors and Collaborators

H3 Biomedicine Inc.

Eisai Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02841540
Other Study ID Numbers: 2016-001792-70
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Eisai Inc.:

Myelodysplastic Syndromes

Acute Myeloid Leukemia

Chronic Myelomonocytic Leukemia

H3B-8800

Splicing Modulator

CMML

AML

MDS

Additional relevant MeSH terms:

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Myelodysplastic Syndromes

Preleukemia

Leukemia, Myelomonocytic, Acute

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on July 18, 2019