Phase 2
Completed N=45
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)
Source: ClinicalTrials.gov NCT02842827 ↗Enrolled (actual)
45
Serious AEs
97.8%
Results posted
Jul 2023
Primary outcomePrimary: Number of Participants Who Experienced an Adverse Event (AE) — 3; 6; 4; 6 Participants
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Experienced an Adverse Event (AE) |
3; 6; 4; 6; 5; 9 | — |
| PRIMARY Number of Participants Who Experienced a Serious Adverse Event (SAE) |
3; 6; 4; 5; 5; 9 | — |
| PRIMARY Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) |
2; 2; 3; 3; 0; 1 | — |
| PRIMARY Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants Experiencing Any Grade 3 to 5 Adverse Events (AE) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 |
3; 6; 4; 5; 5; 9 | — |
| PRIMARY Number of Participants Who Experienced a Medical Event of Interest (MEOI) |
1; 1; 1; 2; 0; 3 | — |
| PRIMARY Maximum Concentration (Cmax) of Bomedemstat Alone or Administered With Tretinoin |
10.7; 19.6; 65.7; 145; 66.8; 205 | — |
| PRIMARY Time to Maximum Concentration (Tmax) of Bomedemstat Alone or Administered With Tretinoin |
1.00; 2.00; 1.00; 2.06; 1.00; 1.02 | — |
| PRIMARY Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC0-24hr) Postdose of Bomedemstat Alone or Administered With Tretinoin |
26.4; 78.6; 323; 1361; 287; 1138 | — |
| PRIMARY Elimination Half Life (t1/2) of Bomedemstat Alone or Administered With Tretinoin |
130; 103; 103; 110; 59.8 | — |
| PRIMARY Apparent Total Body Clearance (CL/F) of Bomedemstat Alone or Administered With Tretinoin |
5.754; 1.351; 492; 401; 472; 287 | — |
| PRIMARY Volume of Distribution (Vz/F) of Bomedemstat Alone or Administered With Tretinoin |
56354; 224527; 99822; 63895; 22539 | — |
| PRIMARY Terminal Elimination Rate Constant (Kel) of Bomedemstat Alone or Administered With Tretinoin |
0.0053; 0.0071; 0.0068; 0.0074; 0.0135 | — |
| PRIMARY Event-free Survival (EFS) For High-risk Acute Myeloid Leukemia (AML) Participants |
0.87; 0.97; 0.93; 2.46; 0.93; NA | — |
| PRIMARY Event-free Survival (EFS) For High-risk Myelodysplastic Syndromes (MDS) Participants |
NA; 0.75; NA; NA | — |
| PRIMARY Overall Survival (OS) For High-risk Acute Myeloid Leukemia (AML) Participants |
NA; NA; 18.81; 3.86; NA; NA | — |
| PRIMARY Overall Survival (OS) For High-risk Myelodysplastic Syndromes (MDS) Participants |
NA; NA; NA; NA | — |
| PRIMARY Objective Response Rate (ORR) For High-risk Acute Myeloid Leukemia (AML) Participants Determined Using the Revised/Modified International Working Group (IWG) Response Criteria (Cheson et al., 2003) and Assessed by the Investigator |
50.0; 16.7; 25.0; 50.0; 33.3; 28.6 | — |
| PRIMARY Best Overall Response (BOR) For High-risk Acute Myeloid Leukemia (AML) Participants Determined Using the Revised/Modified International Working Group (IWG) Response Criteria (Cheson et al., 2003) and Assessed by the Investigator |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Objective Response Rate (ORR) For High-risk Myelodysplastic Syndromes (MDS) Participants Determined Using the Revised/Modified International Working Group (IWG) Response Criteria (Cheson et al., 2006) and Assessed by the Investigator |
100.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Best Overall Response (BOR) Assessed by the Revised/Modified International Working Group (IWG) Response Criteria (Cheson et al., 2006): High-risk Myelodysplastic Syndromes (MDS) Participants |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Maximum Percent Change From Baseline Up to 28 Days of Treatment in Erythrocyte Count in Whole Blood After Administration of Bomedemstat |
4.4; 16.7; 17.0; 21.4 | 0.3868 |
| SECONDARY Maximum Percent Change From Baseline Up to 28 Days of Treatment in Neutrophil Count in Whole Blood After Administration of Bomedemstat |
198.4; 223.3; 198.8; 3218.0 | 0.7744 |
| SECONDARY Maximum Percent Change From Baseline Up to 28 Days of Treatment in Platelet Count in Whole Blood After Administration of Bomedemstat |
21.9; 30.4; 313.6; 8.1 | 0.5080 |
| SECONDARY Maximum Percent Change From Baseline Up to 28 Days of Treatment in Reticulocyte Count in Whole Blood After Administration of Bomedemstat |
47.3; 57.1; 133.5; 26.6 | 0.6109 |
| SECONDARY Maximum Percent Change From Baseline Up to 28 Days of Treatment in The Number of Blasts in Whole Blood After Administration of Bomedemstat |
368.0; 2478.3; 9.7; 2841.4 | 0.1151 |
| SECONDARY Maximum Percent Change From Baseline Up to 28 Days of Treatment in Hemoglobin Level in Whole Blood After Administration of Bomedemstat |
1262.1; 476.5; 12.6; 134.4 | 0.0791 |
Eligibility Criteria
The main inclusion and exclusion criteria include but are not limited to the following:
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
Data sourced from ClinicalTrials.gov (NCT02842827). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.