A Study of Bomedemstat (IMG-7289/MK-3543) With and Without ATRA, in Participants With Advanced Myeloid Malignancies (IMG-7289-CTP-101/MK-3543-001)

NCT ID: NCT02842827

Last Updated: 2023-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-06
• Study Completion Date: 2018-10-30

Brief Summary

This is an open label study of the dose and duration of an orally administered lysine-specific demethylase 1 (LSD1) inhibitor, bomedemstat, in patients with high-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Some participants may also receive all-trans retinoic acid (ATRA; also known as tretinoin and Vesanoid®) in combination with bomedemstat. This study investigates the following:

• The safety and tolerability of bomedemstat with and without ATRA
• The pharmacodynamic effect of different doses of bomedemstat and treatment durations, as well as bomedemstat administered in combination with ATRA
• The pharmacokinetics of bomedemstat with and without ATRA

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1a: bomedemstat 0.75 mg/kg/day

Participants receive bomedemstat 0.75 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Group Type: EXPERIMENTAL

bomedemstat

Intervention Type: DRUG

oral administration

Cohort 1b: bomedemstat 1.5 mg/kg/day

Participants receive bomedemstat 1.5 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Group Type: EXPERIMENTAL

bomedemstat

Intervention Type: DRUG

oral administration

Cohort 1c: bomedemstat 3 mg/kg/day

Participants receive bomedemstat 3 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Group Type: EXPERIMENTAL

bomedemstat

Intervention Type: DRUG

oral administration

Cohort 1d: bomedemstat 6 mg/kg/day orally

Participants receive bomedemstat 6 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Group Type: EXPERIMENTAL

bomedemstat

Intervention Type: DRUG

oral administration

Cohort 1x3: bomedemstat 3 mg/kg/day orally plus tretinoin 45 mg/m^2 /day3

Participants receive bomedemstat 3 mg/kg/day orally plus tretinoin 45 mg/m\^2/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Group Type: EXPERIMENTAL

bomedemstat

Intervention Type: DRUG

oral administration

tretinoin

Intervention Type: DRUG

oral administration

Cohort 1x6: bomedemstat 6 mg/kg/day plus tretinoin 45 mg/m^2/day

Participants receive bomedemstat 6 mg/kg/day orally plus tretinoin 45 mg/m\^2/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Group Type: EXPERIMENTAL

bomedemstat

Intervention Type: DRUG

oral administration

tretinoin

Intervention Type: DRUG

oral administration

Cohort 3x: bomedemstat 6 mg/kg/day plus tretinoin 45 mg/m^2/day

Participants receive bomedemstat 6 mg/kg/day orally plus tretinoin 45 mg/m\^2/day orally in 21-day cycles consisting of 14 days of treatment and 7 days of rest. Participants will receive up to 2 cycles (21-day cycles) for up to a total of up 42 days (28 days on treatment).

Group Type: EXPERIMENTAL

bomedemstat

Intervention Type: DRUG

oral administration

tretinoin

Intervention Type: DRUG

oral administration

Cohort 4x: bomedemstat 6 mg/kg/day plus tretinoin 45 mg/m^2/day

Participants receive bomedemstat 6 mg/kg/day orally for 21 days plus tretinoin 45 mg/m\^2/day orally in 28-day cycles consisting of 21 days of treatment and 7 days of rest. Participants will receive at least 1 cycle (28-day cycles) and will receive subsequent cycles at the discretion of the investigator.

Group Type: EXPERIMENTAL

bomedemstat

Intervention Type: DRUG

oral administration

tretinoin

Intervention Type: DRUG

oral administration

Interventions

bomedemstat

oral administration

Intervention Type: DRUG

tretinoin

oral administration

Intervention Type: DRUG

Other Intervention Names

MK-3543; IMG-7289; ATRA®; Vesanoid®; all-trans retinoic acid,

Eligibility Criteria

Inclusion Criteria

High-risk Acute Myeloid Leukemia (AML)

• Have a diagnosis of AML according to the World Health Organization (WHO) criteria
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
• Have AML that is classified as high risk as defined by one of the following: ≥ 60 years of age who were not candidates for or have refused standard chemotherapy; ≥18 years of age with de novo or secondary AML who were not expected to benefit from standard remission-induction chemotherapy; or had relapsed/refractory AML after no more than 3 previous lines of chemotherapy.

High-risk Myelodysplastic Syndromes (MDS)

• Have a diagnosis of myelodysplastic syndromes according to the World Health Organization (WHO) criteria
• Have either an International Prognostic Scoring System (IPSS) score equivalent to intermediate-2 risk or higher, or a Revised International Prognostic Scoring System (IPSS-R) score equivalent to intermediate risk or higher.
• Have MDS that is classified as high risk as defined by one of the following: participants who have failed first-line therapy; or treatment-related MDS, except if it is associated with favorable cytogenetics, and not a candidate for stem cell transplantation
• Prior autologous stem cell transplant is allowed if a minimum of 3 months has elapsed from the time of transplant and the patient has recovered from transplant-associated toxicities
• Prior allogeneic stem cell transplant is allowed, provided all of the following criteria are met: transplant was >120 days prior to study enrollment; no immunosuppressive medications have been taken for at least 1 month; and no active graft versus host disease (GVHD), excluding Grade 1 skin GVHD
• Has a life expectancy >12 weeks

Exclusion Criteria

• Is receiving other treatments for the condition (with exceptions and time limits)
• Has had major surgery in last 4 weeks or minor surgery in the last 2 weeks
• Has a scheduled hematopoietic stem-cell transplant
• Is currently using prohibited medications
• Has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia
• Has a concurrent second active and non-stable malignancy
• Has an uncontrolled active infection
• Has known Human Immunodeficiency Virus (HIV) infection or active Hepatitis B or Hepatitis C virus infection
• Has used an investigational agent within last 14 days
• Is a pregnant or lactating females

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Countries

Australia

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IMG-7289-CTP-101

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3543-001

Identifier Type: OTHER

Identifier Source: secondary_id

IMG-7289-CTP-101

Identifier Type: -

Identifier Source: org_study_id