Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT05453903
Registration number
NCT05453903
Ethics application status
Date submitted
8/07/2022
Date registered
12/07/2022
Date last updated
23/05/2025
Titles & IDs
Public title
A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies
Query!
Scientific title
A Phase 1b Study of Bleximenib in Combination With AML-Directed Therapies for Participants With Acute Myeloid Leukemia Harboring KMT2A or NPM1 Alterations
Query!
Secondary ID [1]
0
0
75276617ALE1002
Query!
Secondary ID [2]
0
0
CR109124
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Leukemia, Myeloid, Acute
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Leukaemia - Acute leukaemia
Query!
Cancer
0
0
0
0
Query!
Leukaemia - Chronic leukaemia
Query!
Cancer
0
0
0
0
Query!
Children's - Leukaemia & Lymphoma
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Bleximenib
Treatment: Drugs - Venetoclax (VEN)
Treatment: Drugs - Azacitidine (AZA)
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin or Idarubicin
Experimental: Arm A: Relapsed/Refractory Setting - Participants with relapsed/refractory AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations will receive bleximenib in combination with either venetoclax (VEN) (Cohort A1: bleximenib+VEN) or azacitidine (AZA) (Cohort A2: bleximenib +AZA) or VEN+AZA (Cohort A3: bleximenib+VEN+AZA) or VEN + AZA (Cohort A4: bleximenib + VEN + AZA) in adolescent participants aged greater than or equal to (\>=) 12 years and less than (\<) 18 years of age, to select the recommended phase 2 dose (RP2D) of bleximenib in combination with VEN, AZA or VEN+AZA (dose selection). In dose expansion portion of the study, participants will receive bleximenib in combination with AML directed therapies at the RP2D(s).
Experimental: Arm B: Newly Diagnosed Chemotherapy Ineligible Setting - Participants will receive bleximenib in combination with VEN+AZA as frontline chemo therapy for newly diagnosed AML participants harboring KMT2A, NPM1, NUP98, or NUP214 alterations who are \>=75 years of age or \>=18 years of age to \<75 years of age with comorbidities that preclude the use of intensive induction chemotherapy.
Experimental: Arm C: Newly Diagnosed Chemotherapy Eligible Setting - Participants will receive combination of bleximenib with cytarabine+daunorubicin or idarubicin chemotherapy as frontline treatment regimen for participants \>= 18 to \<75 years of age with AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations and eligible for intensive chemotherapy.
Treatment: Drugs: Bleximenib
Participants will receive bleximenib.
Treatment: Drugs: Venetoclax (VEN)
Participants will receive VEN.
Treatment: Drugs: Azacitidine (AZA)
Participants will receive AZA.
Treatment: Drugs: Cytarabine
Participants will receive cytarabine.
Treatment: Drugs: Daunorubicin or Idarubicin
Participants will receive daunorubicin or idarubicin.
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of Participants with Adverse Events (AEs)
Query!
Assessment method [1]
0
0
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Query!
Timepoint [1]
0
0
Up to 3 Years 3 months
Query!
Primary outcome [2]
0
0
Number of Participants with Adverse Events (AEs) by Severity
Query!
Assessment method [2]
0
0
Number of Participants with AEs by severity will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Query!
Timepoint [2]
0
0
Up to 3 Years 3 months
Query!
Primary outcome [3]
0
0
Number of Participants with Dose-limiting Toxicity (DLT)
Query!
Assessment method [3]
0
0
Number of participants with DLT will be reported according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Query!
Timepoint [3]
0
0
End of Cycle 1 (28 days)
Query!
Secondary outcome [1]
0
0
Plasma Concentration of Bleximenib
Query!
Assessment method [1]
0
0
Plasma samples will be analyzed to determine concentrations of bleximenib using a validated, specific, and sensitive method.
Query!
Timepoint [1]
0
0
Up to 3 Years 3 months
Query!
Secondary outcome [2]
0
0
Number of Participants with Depletion of Leukemic Blasts
Query!
Assessment method [2]
0
0
Number of participants with depletion of leukemic blasts will be reported.
Query!
Timepoint [2]
0
0
Up to 3 Years 3 months
Query!
Secondary outcome [3]
0
0
Percentage of Participants who Achieve Complete Remission (CR)
Query!
Assessment method [3]
0
0
Percentage of participants who achieve complete Remission (CR) will be reported. CR is defined as Bone marrow blasts less than (\<) 5 percent (%); Absence of circulating blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (\>=) 1.0\*10\^9/Liter (L) (1,000/microliter \[mcL\]); Platelet count \>= 100 \* 10\^9/L (100,000/mcL).
Query!
Timepoint [3]
0
0
Up to 3 Years 3 months
Query!
Secondary outcome [4]
0
0
Percentage of Participants who Achieve Complete Remission with Partial Hematologic Recovery (CRh)
Query!
Assessment method [4]
0
0
Percentage of participants who achieve complete remission with partial hematologic recovery (CRh) will be reported. CRh is defined as All criteria of CR with both ANC \>0.5 \* 10\^9/L (500/mcL) and platelet count \>50 \* 10\^9/L (50,000/mcL).
Query!
Timepoint [4]
0
0
Up to 3 Years 3 months
Query!
Secondary outcome [5]
0
0
Percentage of Participants who Achieve Complete Remission with Incomplete Hematologic Recovery (CRi)
Query!
Assessment method [5]
0
0
Percentage of participants who achieve complete remission with incomplete hematologic recovery (CRi) will be reported. CRi is defined as All CR criteria except for residual neutropenia (\<1.0\*10\^9/L \[1,000/mcL\]) or thrombocytopenia (\<100 \* 10\^9/L \[100,000/mcL\]).
Query!
Timepoint [5]
0
0
Up to 3 Years 3 months
Query!
Secondary outcome [6]
0
0
Percentage of Participants who Achieved Overall Response
Query!
Assessment method [6]
0
0
Percentage of participants who achieve overall response will be reported. Overall response rate (ORR) is defined as the percentage of participants achieving CR, CRh, or CRi, morphologic leukemia-free state (MLFS) or partial remission (PR).
Query!
Timepoint [6]
0
0
Up to 3 Years 3 months
Query!
Eligibility
Key inclusion criteria
* Adolescent participants (defined as greater than or equal to [>=] 12 and less than [<] 18 years of age) are only eligible for the relapsed/refractory (R/R) cohort (Arm A, cohort A4)
* Diagnosis of AML according to World Health Organization (WHO) criteria: a) De novo or secondary AML; b) relapsed/refractory (Arm A only); c) harboring KMT2A, NPM1, NUP98, or NUP214 alterations; d) Participants may receive emergency leukapheresis and/or cytarabine as cytoreductive therapy according to local practice guidelines
* Pretreatment clinical laboratory values meeting the following criteria -listed below: White blood cell (WBC) count: less than or equal to (<=) 25*10^9 per liter (/L), adequate liver and renal function
* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Adolescent participants only: Performance status >70 by Lansky scale (for participants <16 years of age) or >70 Karnofsky scale (for participants >16 years of age)
* A female of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin at screening and within 48 hours prior to the first dose of study treatment
* Must sign an informed consent form (ICF) indicating participant (or their legally authorized representative) understands the purpose of the study and procedures required for the study and is willing to participate in the study
* Willing and able to adhere to the prohibitions and restrictions specified in this protocol
Query!
Minimum age
12
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic leukemia according to WHO 2016 criteria
* Leukemic involvement of the central nervous system
* Recipient of solid organ transplant
* Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes or that was diagnosed within 6 months prior to the first dose of study treatment including, but not limited to: (a) Myocardial infarction; (b) Severe or unstable angina; (c) Clinically significant cardiac arrhythmias, including bradycardia (<50 beats per minute); (d) Uncontrolled (persistent) hypertension: (example, blood pressure greater than [>] 140/90 millimeters of mercury [mm Hg]; (e) Acute neurologic events such as stroke or transient ischemic attack, intracranial or subarachnoid hemorrhage, intracranial trauma; (f) Venous thromboembolic events (example, pulmonary embolism) within 1 month prior to the first dose of study treatment ;(g) Congestive heart failure (NYHA class III to IV); (h) Pericarditis or clinically significant pericardial effusion; (i) Myocarditis; (j) Endocarditis (k) Clinically significant hypokalemia, hypomagnesemia, hypocalcemia (corrected for hypoalbuminemia)
* Any toxicity (except for alopecia, stable peripheral neuropathy, thrombocytopenia, neutropenia, anemia) from previous anticancer therapy that has not resolved to baseline or to grade 1 or less
* Pulmonary compromise that requires the need for supplemental oxygen use to maintain adequate oxygenation
* Participants with diagnosis of Fanconi anemia, Kostmann syndrome, Shwachman diamond syndrome, or any other known bone marrow failure syndrome
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Other
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
4/10/2022
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
19/03/2027
Query!
Actual
Query!
Sample size
Target
200
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment hospital [1]
0
0
Monash Medical Centre - Clayton
Query!
Recruitment hospital [2]
0
0
Peter MacCallum Cancer Centre - Melbourne
Query!
Recruitment hospital [3]
0
0
Westmead Hospital - Westmead
Query!
Recruitment postcode(s) [1]
0
0
3168 - Clayton
Query!
Recruitment postcode(s) [2]
0
0
3000 - Melbourne
Query!
Recruitment postcode(s) [3]
0
0
2145 - Westmead
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Alabama
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Massachusetts
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
New York
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
North Carolina
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Texas
Query!
Country [7]
0
0
Canada
Query!
State/province [7]
0
0
Ontario
Query!
Country [8]
0
0
France
Query!
State/province [8]
0
0
Marseille Cedex 9
Query!
Country [9]
0
0
France
Query!
State/province [9]
0
0
Rennes Cedex 9
Query!
Country [10]
0
0
France
Query!
State/province [10]
0
0
Toulouse Cedex 9
Query!
Country [11]
0
0
France
Query!
State/province [11]
0
0
Tours
Query!
Country [12]
0
0
Germany
Query!
State/province [12]
0
0
Berlin
Query!
Country [13]
0
0
Germany
Query!
State/province [13]
0
0
Dresden
Query!
Country [14]
0
0
Germany
Query!
State/province [14]
0
0
Heidelberg
Query!
Country [15]
0
0
Germany
Query!
State/province [15]
0
0
Leipzig
Query!
Country [16]
0
0
Germany
Query!
State/province [16]
0
0
Ulm
Query!
Country [17]
0
0
Italy
Query!
State/province [17]
0
0
Bologna
Query!
Country [18]
0
0
Italy
Query!
State/province [18]
0
0
Meldola
Query!
Country [19]
0
0
Italy
Query!
State/province [19]
0
0
Milano
Query!
Country [20]
0
0
Italy
Query!
State/province [20]
0
0
Rozzano
Query!
Country [21]
0
0
Spain
Query!
State/province [21]
0
0
Barcelona
Query!
Country [22]
0
0
Spain
Query!
State/province [22]
0
0
Madrid
Query!
Country [23]
0
0
Spain
Query!
State/province [23]
0
0
Pamplona
Query!
Country [24]
0
0
United Kingdom
Query!
State/province [24]
0
0
London
Query!
Country [25]
0
0
United Kingdom
Query!
State/province [25]
0
0
Manchester
Query!
Country [26]
0
0
United Kingdom
Query!
State/province [26]
0
0
Oxfordshire
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Janssen Research & Development, LLC
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The purpose of this study is to determine the recommended Phase 2 dose (RP2D) candidate(s) of bleximenib in combination with AML directed therapies (dose selection) and further to evaluate safety and tolerability of bleximenib in combination with AML directed therapies at the RP2D(s) (dose expansion).
Query!
Trial website
https://clinicaltrials.gov/study/NCT05453903
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Janssen Research & Development, LLC Clinical Trial
Query!
Address
0
0
Janssen Research & Development, LLC
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Study Contact
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
844-434-4210
Query!
Fax
0
0
Query!
Email
0
0
[email protected]
Query!
Contact person for scientific queries
Data sharing statement
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT05453903
Download to PDF