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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02842827




Registration number
NCT02842827
Ethics application status
Date submitted
12/07/2016
Date registered
25/07/2016

Titles & IDs
Public title
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)
Scientific title
A Multi-Center, Open Label Study to Assess the Safety, Steady-State Pharmacokinetics and Pharmacodynamics of IMG-7289 With and Without ATRA (Tretinoin) in Patients With Advanced Myeloid Malignancies
Secondary ID [1] 0 0
IMG-7289-CTP-101
Secondary ID [2] 0 0
IMG-7289-CTP-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Myelodysplastic Syndrome 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - bomedemstat
Treatment: Drugs - tretinoin

Experimental: 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).

Experimental: 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).

Experimental: 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).

Experimental: 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).

Experimental: 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).

Experimental: 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).

Experimental: 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).

Experimental: 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.


Treatment: Drugs: bomedemstat
oral administration

Treatment: Drugs: tretinoin
oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [1] 0 0
Up to approximately 24 months
Primary outcome [2] 0 0
Number of Participants Who Experienced a Serious Adverse Event (SAE)
Timepoint [2] 0 0
Up to approximately 24 months
Primary outcome [3] 0 0
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Timepoint [3] 0 0
Up to approximately 18 months
Primary outcome [4] 0 0
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
Timepoint [4] 0 0
Up to approximately 28 Days
Primary outcome [5] 0 0
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
Timepoint [5] 0 0
Up to approximately 24 months
Primary outcome [6] 0 0
Number of Participants Who Experienced a Medical Event of Interest (MEOI)
Timepoint [6] 0 0
Up to approximately 24 months
Primary outcome [7] 0 0
Maximum Concentration (Cmax) of Bomedemstat Alone or Administered With Tretinoin
Timepoint [7] 0 0
Cycle 1 Day 1: predose and 1, 2, 3, and 24 hours postdose; Day 7: predose and 0.5, 1, 2, 3, 4, 8, and 24 hours postdose
Primary outcome [8] 0 0
Time to Maximum Concentration (Tmax) of Bomedemstat Alone or Administered With Tretinoin
Timepoint [8] 0 0
Cycle 1 Day 1: predose and 1, 2, 3, and 24 hours postdose; Day 7: predose and 0.5, 1, 2, 3, 4, 8, and 24 hours postdose
Primary outcome [9] 0 0
Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC0-24hr) Postdose of Bomedemstat Alone or Administered With Tretinoin
Timepoint [9] 0 0
Cycle 1 Day 1: predose and 1, 2, 3, and 24 hours postdose; Day 7: predose and 0.5, 1, 2, 3, 4, 8, and 24 hours postdose
Primary outcome [10] 0 0
Elimination Half Life (t1/2) of Bomedemstat Alone or Administered With Tretinoin
Timepoint [10] 0 0
Cycle 1 Day 7: predose and 0.5, 1, 2, 3, 4, 8, and 24 hours postdose
Primary outcome [11] 0 0
Apparent Total Body Clearance (CL/F) of Bomedemstat Alone or Administered With Tretinoin
Timepoint [11] 0 0
Cycle 1 Day 7: predose and 0.5, 1, 2, 3, 4, 8, and 24 hours postdose
Primary outcome [12] 0 0
Volume of Distribution (Vz/F) of Bomedemstat Alone or Administered With Tretinoin
Timepoint [12] 0 0
Cycle 1 Day 7: predose and 0.5, 1, 2, 3, 4, 8, and 24 hours postdose
Primary outcome [13] 0 0
Terminal Elimination Rate Constant (Kel) of Bomedemstat Alone or Administered With Tretinoin
Timepoint [13] 0 0
Cycle 1 Day 7: predose and 0.5, 1, 2, 3, 4, 8, and 24 hours postdose
Primary outcome [14] 0 0
Event-free Survival (EFS) For High-risk Acute Myeloid Leukemia (AML) Participants
Timepoint [14] 0 0
Up to approximately 24 months
Primary outcome [15] 0 0
Event-free Survival (EFS) For High-risk Myelodysplastic Syndromes (MDS) Participants
Timepoint [15] 0 0
Up to approximately 24 months
Primary outcome [16] 0 0
Overall Survival (OS) For High-risk Acute Myeloid Leukemia (AML) Participants
Timepoint [16] 0 0
Up to approximately 24 months
Primary outcome [17] 0 0
Overall Survival (OS) For High-risk Myelodysplastic Syndromes (MDS) Participants
Timepoint [17] 0 0
Up to approximately 24 months
Primary outcome [18] 0 0
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
Timepoint [18] 0 0
Up to approximately 24 months
Primary outcome [19] 0 0
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
Timepoint [19] 0 0
Up to approximately 24 months
Primary outcome [20] 0 0
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
Timepoint [20] 0 0
Up to approximately 24 months
Primary outcome [21] 0 0
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
Timepoint [21] 0 0
Up to approximately 24 months
Secondary outcome [1] 0 0
Maximum Percent Change From Baseline Up to 28 Days of Treatment in Erythrocyte Count in Whole Blood After Administration of Bomedemstat
Timepoint [1] 0 0
Baseline (prior to first dose of study drug) and up to 28 days
Secondary outcome [2] 0 0
Maximum Percent Change From Baseline Up to 28 Days of Treatment in Neutrophil Count in Whole Blood After Administration of Bomedemstat
Timepoint [2] 0 0
Baseline (prior to first dose of study drug) and up to 28 days
Secondary outcome [3] 0 0
Maximum Percent Change From Baseline Up to 28 Days of Treatment in Platelet Count in Whole Blood After Administration of Bomedemstat
Timepoint [3] 0 0
Baseline (prior to first dose of study drug) and up to 28 days
Secondary outcome [4] 0 0
Maximum Percent Change From Baseline Up to 28 Days of Treatment in Reticulocyte Count in Whole Blood After Administration of Bomedemstat
Timepoint [4] 0 0
Baseline (prior to first dose of study drug) and up to 28 days
Secondary outcome [5] 0 0
Maximum Percent Change From Baseline Up to 28 Days of Treatment in The Number of Blasts in Whole Blood After Administration of Bomedemstat
Timepoint [5] 0 0
Baseline (prior to first dose of study drug) and up to 28 days
Secondary outcome [6] 0 0
Maximum Percent Change From Baseline Up to 28 Days of Treatment in Hemoglobin Level in Whole Blood After Administration of Bomedemstat
Timepoint [6] 0 0
Baseline (prior to first dose of study drug) and up to 28 days

Eligibility
Key inclusion criteria
The main inclusion and exclusion criteria include but are not limited to the following:



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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/10/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/10/2018
Sample size
Target
Accrual to date
Final
45
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02842827