A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia
- Conditions
- Acute Lymphoblastic LeukemiaAcute LeukemiasAcute Myeloid Leukemia
- Interventions
- Drug: Bleximenib
- Registration Number
- NCT04811560
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Bleximenib 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.
- Primary Outcome Measures
Name Time Method Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability Up to 4 years and 9 months 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.
Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT) Up to 28 days Cycle 1 Percentage of participants with DLT will be assessed accordingly to national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 5.
Phase 1: Number of Participants with AEs by Severity Up to 4 years and 9 months 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.
Phase 2: Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh) Up to 4 years and 9 months Rate of CR/CRh is defined as the percentage of participants achieving a CR or CRh at any time post-treatment.
- Secondary Outcome Measures
Name Time Method Phase 1 and 2: Plasma Concentration of Bleximenib Up to 4 years and 9 months Plasma concentration of bleximenib will be reported.
Phase 1 and 2: Overall Response Rate (ORR) Up to 4 years and 9 months ORR is defined as the percentage of participants who achieve any response.
Phase 1 and 2: Duration of Response (DOR) Up to 4 years and 9 months 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.
Phase 1 and 2: Time To Response (TTR) Up to 4 years and 9 months 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.
Phase 2: Duration of Complete Response (CR)/Complete Remission With Partial Hematologic Recovery (CRh) Up to 4 years and 9 months 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.
Phase 2: Time To CR/CRh Up to 4 years and 9 months 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.
Phase 2: Event-free survival (EFS) Up to 4 years and 9 months 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.
Phase 2: Overall survival (OS) Up to 4 years and 9 months OS is defined from the date of first dose of study treatment to the date of death due to any cause.
Phase 2: Measurable Residual Disease (MRD) Negativity Among Participants Achieving CR/CRh/CRi Up to 4 years and 9 months 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.
Phase 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to 4 years and 9 months 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.
Phase 2: Number of Participants Reporting Transfusion Independence Up to 4 years and 9 months Transfusion independence is defined as independence from red blood cells (RBC) and platelet transfusions during any 56-day interval after receiving study treatment.
Trial Locations
- Locations (64)
West China Hospital Si Chuan University
🇨🇳Chengdu, China
Nanfang Hospital of Southern Medical Hospital
🇨🇳Guangzhou, China
Sheba Medical Center
🇮🇱Ramat Gan, Israel
University Hospitals Plymouth NHS Trust
🇬🇧Plymouth, United Kingdom
City of Hope
🇺🇸Duarte, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation
🇺🇸Indianapolis, Indiana, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Start Midwest
🇺🇸Grand Rapids, Michigan, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
Oregon Health And Science University
🇺🇸Portland, Oregon, United States
Maine Health
🇺🇸Providence, Rhode Island, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
MD Anderson
🇺🇸Houston, Texas, United States
San Antonio Methodist TX Transplant Physicians Group
🇺🇸San Antonio, Texas, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Medical College of WI at Froedtert
🇺🇸Milwaukee, Wisconsin, United States
Monash Medical Centre
🇦🇺Clayton, Australia
Royal Perth Hospital
🇦🇺Perth, Australia
Gold Coast University Hospital
🇦🇺Southport, Australia
Hopital Jean Minjoz
🇫🇷Besancon, France
Institut Paoli Calmettes
🇫🇷Marseille, France
CHU de Nantes hotel Dieu
🇫🇷Nantes Cedex 1, France
Hopital Saint Louis
🇫🇷Paris, France
Hopital trousseau- APHP
🇫🇷Paris, France
Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie
🇫🇷Pessac, France
CHU Lyon Sud
🇫🇷Pierre Benite, France
Institut de Cancerologie Strasbourg Europe ICANS
🇫🇷Strasbourg, France
Institut Universitaire du Cancer Toulouse Oncopole
🇫🇷Toulouse, France
CHU Bretonneau
🇫🇷Tours cedex, France
CHRU Nancy Brabois
🇫🇷Vandoeuvre les Nancy, France
Gustave Roussy
🇫🇷Villejuif, France
Carmel Medical Center
🇮🇱Haifa, Israel
Hadassah University Hospita Ein Kerem
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv Yafo, Israel
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Nagoya University Hospital
🇯🇵Nagoya, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Japan
NTT Medical Center Tokyo
🇯🇵Tokyo, Japan
University of Fukui Hospital
🇯🇵Yoshida, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Hosp. Gral. Univ. Gregorio Maranon
🇪🇸Madrid, Spain
Hosp Univ Fund Jimenez Diaz
🇪🇸Madrid, Spain
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
Hosp Clinico Univ de Salamanca
🇪🇸Salamanca, Spain
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Hosp. Clinico Univ. de Valencia
🇪🇸Valencia, Spain
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Guys and St Thomas NHS Foundation Trust
🇬🇧London, United Kingdom
The Christie Nhs Foundation Trust
🇬🇧Manchester, United Kingdom
Oxford University Hospitals NHS Trust
🇬🇧Oxfordshire, United Kingdom