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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04811560




Registration number
NCT04811560
Ethics application status
Date submitted
22/03/2021
Date registered
23/03/2021

Titles & IDs
Public title
A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia
Scientific title
A Phase 1/2, First-in-Human Study of the Menin-KMT2A (MLL1) Inhibitor Bleximenib in Participants With Acute Leukemia
Secondary ID [1] 0 0
2020-005967-30
Secondary ID [2] 0 0
CR108998
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Leukemias 0 0
Acute Myeloid Leukemia 0 0
Acute Lymphoblastic Leukemia 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
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

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

Experimental: Bleximenib - Participants in Phase 1 Part 1 (dose escalation) will receive bleximenib orally. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Doses (RP2Ds) have been identified. Participants in Phase 1 Part 2 (dose expansion) will receive bleximenib orally at the RP2D(s) determined in Part 1. Food effect cohort (optional) participants will receive bleximenib orally on Cycle 2 Day 1 under fasted condition and on Cycle 2 Day 2 under fed condition. Participants in Phase 2 part of the study will receive bleximenib orally at the RP2D level(s).


Treatment: Drugs: Bleximenib
Bleximenib is administered orally.

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

Outcomes
Primary outcome [1] 0 0
Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Timepoint [1] 0 0
Up to 4 years and 9 months
Primary outcome [2] 0 0
Phase 1: Number of Participants with AEs by Severity
Timepoint [2] 0 0
Up to 4 years and 9 months
Primary outcome [3] 0 0
Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT)
Timepoint [3] 0 0
Up to 28 days Cycle 1
Primary outcome [4] 0 0
Phase 2: Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh)
Timepoint [4] 0 0
Up to 4 years and 9 months
Secondary outcome [1] 0 0
Phase 1: Plasma Concentration of Bleximenib
Timepoint [1] 0 0
Up to 4 years and 9 months
Secondary outcome [2] 0 0
Phase 1 and 2: Overall Response Rate (ORR)
Timepoint [2] 0 0
Up to 4 years and 9 months
Secondary outcome [3] 0 0
Phase 1 and 2: Duration of Response (DOR)
Timepoint [3] 0 0
Up to 4 years and 9 months
Secondary outcome [4] 0 0
Phase 1 and 2: Time To Response (TTR)
Timepoint [4] 0 0
Up to 4 years and 9 months
Secondary outcome [5] 0 0
Phase 2: Event-free survival (EFS)
Timepoint [5] 0 0
Up to 4 years and 9 months
Secondary outcome [6] 0 0
Phase 2: Overall survival (OS)
Timepoint [6] 0 0
Up to 4 years and 9 months
Secondary outcome [7] 0 0
Phase 2: Measurable Residual Disease (MRD) Negativity Among Participants Achieving CR/CRh/CRi
Timepoint [7] 0 0
Up to 4 years and 9 months
Secondary outcome [8] 0 0
Phase 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [8] 0 0
Up to 4 years and 9 months
Secondary outcome [9] 0 0
Phase 2: Number of Participants Reporting Transfusion Independence
Timepoint [9] 0 0
Up to 4 years and 9 months
Secondary outcome [10] 0 0
Phase 2: Maximum Plasma Concentration (Cmax) of Bleximenib
Timepoint [10] 0 0
Up to 4 years and 9 months
Secondary outcome [11] 0 0
Phase 2: Time to Reach the Maximum Concentration (Tmax) of Bleximenib
Timepoint [11] 0 0
Up to 4 years and 9 months
Secondary outcome [12] 0 0
Phase 2: Area Under the Plasma Concentration-time Curve (AUC) from Time T1 to T2 of Bleximenib
Timepoint [12] 0 0
Up to 4 years and 9 months
Secondary outcome [13] 0 0
Phase 2: Area Under The Curve Over a Dosing Interval (AUCtau) of Bleximenib
Timepoint [13] 0 0
Up to 4 years and 9 months
Secondary outcome [14] 0 0
Phase 2: Apparent Clearance (CL/F) of Bleximenib
Timepoint [14] 0 0
Up to 4 years and 9 months
Secondary outcome [15] 0 0
Phase 2: Apparent Volume of Distribution (V/F) of Bleximenib
Timepoint [15] 0 0
Up to 4 years and 9 months

Eligibility
Key inclusion criteria
Phase 1:

* Relapsed or refractory (R/R) acute leukemia and has exhausted, or is ineligible for, available therapeutic options
* Participants greater than or equal (>=)12 and less than (<) 18 years of age with a body weight of >= 40 kg are only eligible for the Phase 1 adolescent cohort
* Acute leukemia harboring histone-lysine N-methyltransferase 2A (KMT2A), nucleophosmin 1 gene (NPM1) or nucleoporin 98 gene or nucleoporin 214 gene (NUP98 or NUP214) alterations

Phase: 2

* Participants greater than 18 years are eligible
* Must have had an initial diagnosis of acute myeloid leukemia (AML) per the WHO 2022 classification criteria.
* AML harboring KMT2A-r (gene rearrangement/translocation) or NPM1 mutations only

For Both Phase 1 and 2:

* Pretreatment clinical laboratory values meeting the following criteria: (a) Hematology: white blood cell (WBC) count less than or equal to (<=) 20*10^9/liter (L) and renal function; Estimated or measured glomerular filtration rate greater than or equal to (>=) 50 milliliter per minute (mL/min) per four variable modified diet in renal disease (MDRD) equation
* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Adolescent participants only: Performance status >=70 by Lansky scale (for participants less than [<]16 years of age) or >=70 Karnofsky scale (for participants >=16 years of age)
* A participant 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
* A participant must agree to all the following during the study and for 90 days after the last dose of study treatment: (a) wear a condom when engaging in any activity that allows for passage of ejaculate to another person; (b) not to donate sperm or freeze for future use for the purpose of reproduction. In addition, the participant should be advised of the benefit for a partner to use a highly effective method of contraception as condom may break or leak
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic leukemia according to World Health Organization (WHO) 2016 criteria
* Active central nervous system (CNS) disease
* Prior solid organ transplantation
* QTc according to Fridericia's formula (QTcF) for males >= 450 millisecond (msec) or for females >= 470 msec. Participants with a family history of Long QT syndrome are excluded
* Exclusion criteria related to stem cell transplant: a. Received prior treatment with allogenic bone marrow or stem cell transplant <=3 months before the first dose of study treatment; b. Has evidence of graft versus host disease; c. Received donor lymphocyte infusion <=1 month before the first dose of study treatment; d. Requires immunosuppressant therapy (exception: daily doses <=10 milligrams (mg) prednisone or equivalent are allowed for adrenal replacement)
* Prior cancer immunotherapy within 4 weeks prior to enrollment or blinatumomab within 2 weeks prior to enrollment. Additional prior cancer therapies must not be given within 4 weeks prior to enrollment or 5 half-lives of the agent (whichever is shorter)

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [2] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [3] 0 0
Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
6000 - Perth
Recruitment postcode(s) [3] 0 0
4211 - Southport
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kentucky
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Wisconsin
Country [8] 0 0
France
State/province [8] 0 0
Marseille
Country [9] 0 0
France
State/province [9] 0 0
Nantes Cedex 1
Country [10] 0 0
France
State/province [10] 0 0
Paris
Country [11] 0 0
France
State/province [11] 0 0
Pessac
Country [12] 0 0
France
State/province [12] 0 0
Toulouse
Country [13] 0 0
France
State/province [13] 0 0
Tours cedex
Country [14] 0 0
Spain
State/province [14] 0 0
Barcelona
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
Spain
State/province [16] 0 0
Pamplona
Country [17] 0 0
United Kingdom
State/province [17] 0 0
London
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Manchester
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Oxfordshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
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)?
Yes
What data in particular will be shared?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.janssen.com/clinical-trials/transparency


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.