Brief Summary
The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D\[s\]) of bleximenib in phase 1 (Part 1 \[Dose Escalation\] and to determine the safety and tolerability at RP2D in Phase 1 Part 2 (Dose expansion). The purpose of the Phase 2 part of the study is to evaluate the efficacy of bleximenib at the RP2D.
Brief Title
A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
844-434-4210
Central Contact Email
Participate-In-This-Study1@its.jnj.com
Completion Date
Completion Date Type
Estimated
Conditions
Acute Leukemias
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Eligibility Criteria
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 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 and have relapsed/refractory disease
* 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 (b) 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 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
* Participant must agree to all protocol required contraception requirements and avoid sperm or egg donations or freezing for future reproductive use while on study and for 90 days (males) or 6 months (females) after the last dose of study treatment
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)
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 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 and have relapsed/refractory disease
* 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 (b) 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 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
* Participant must agree to all protocol required contraception requirements and avoid sperm or egg donations or freezing for future reproductive use while on study and for 90 days (males) or 6 months (females) after the last dose of study treatment
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)
Inclusion Criteria
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 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 and have relapsed/refractory disease
* 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 (b) 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 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
* Participant must agree to all protocol required contraception requirements and avoid sperm or egg donations or freezing for future reproductive use while on study and for 90 days (males) or 6 months (females) after the last dose of study treatment
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 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 and have relapsed/refractory disease
* 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 (b) 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 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
* Participant must agree to all protocol required contraception requirements and avoid sperm or egg donations or freezing for future reproductive use while on study and for 90 days (males) or 6 months (females) after the last dose of study treatment
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
12 Years
NCT Id
NCT04811560
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
CR108998
Overall Status
Recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 1/2, First-in-Human Study of the Menin-KMT2A (MLL1) Inhibitor Bleximenib in Participants With Acute Leukemia
Primary Outcomes
Outcome Description
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.
Outcome Measure
Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Outcome Time Frame
Up to 4 years and 9 months
Outcome Description
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.
Outcome Measure
Phase 1: Number of Participants with AEs by Severity
Outcome Time Frame
Up to 4 years and 9 months
Outcome Description
Percentage of participants with DLT will be assessed accordingly to national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 5.
Outcome Measure
Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT)
Outcome Time Frame
Up to 28 days Cycle 1
Outcome Description
Rate of CR/CRh is defined as the percentage of participants achieving a CR or CRh at any time post-treatment.
Outcome Measure
Phase 2: Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh)
Outcome Time Frame
Up to 4 years and 9 months
Secondary Ids
Secondary Id
75276617ALE1001
Secondary Id
2023-506581-31-00
Secondary Outcomes
Outcome Description
Plasma concentration of bleximenib will be reported.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 1 and 2: Plasma Concentration of Bleximenib
Outcome Description
ORR is defined as the percentage of participants who achieve any response.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 1 and 2: Overall Response Rate (ORR)
Outcome Description
DOR will be calculated among responders from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 1 and 2: Duration of Response (DOR)
Outcome Description
TTR is defined for the responders as the time from the date of the first dose of bleximenib to the date of the first documented response.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 1 and 2: Time To Response (TTR)
Outcome Description
The duration of CR/CRh is defined from the date of first CR or CRh response achieved to the date of first evidence of relapsed disease or death due to any cause, whichever occurs first, for participants who achieve a CR or CRh.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 2: Duration of Complete Response (CR)/Complete Remission With Partial Hematologic Recovery (CRh)
Outcome Description
Time to CR/CRh is defined for responders as the time from the date of the first dose of bleximenib to the date of first achieving either CR or CRh, depending on which milestone is reached.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 2: Time To CR/CRh
Outcome Description
EFS is defined as the time from the date of first dose of study treatment to the date of treatment failure, relapse, or death due to any cause, whichever occurs first.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 2: Event-free survival (EFS)
Outcome Description
OS is defined from the date of first dose of study treatment to the date of death due to any cause.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 2: Overall survival (OS)
Outcome Description
MRD-negative rate is defined as the percentage of participants who are MRD-negative at any timepoint after the first dose of bleximenib in the responders.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 2: Measurable Residual Disease (MRD) Negativity Among Participants Achieving CR/CRh/CRi
Outcome Description
An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A Serious AE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Outcome Description
Transfusion independence is defined as independence from red blood cells (RBC) and platelet transfusions during any 56-day interval after receiving study treatment.
Outcome Time Frame
Up to 4 years and 9 months
Outcome Measure
Phase 2: Number of Participants Reporting Transfusion Independence
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org