Clinical trial NCT04811560: A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia
Official title: A Phase 1/2, First-in-Human Study of the Menin-KMT2A (MLL1) Inhibitor Bleximenib in Participants With Acute Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Leukemias
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-03-23
Enrollment: 400
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 4 years and 9 months
measure: Phase 1: Number of Participants with AEs by Severity
timeFrame: Up to 4 years and 9 months
measure: Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT)
timeFrame: Up to 28 days Cycle 1
measure: Phase 2: Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh)
timeFrame: Up to 4 years and 9 months
Secondary outcomes:
measure: Phase 1 and 2: Plasma Concentration of Bleximenib
timeFrame: Up to 4 years and 9 months
measure: Phase 1 and 2: Overall Response Rate (ORR)
timeFrame: Up to 4 years and 9 months
measure: Phase 1 and 2: Duration of Response (DOR)
timeFrame: Up to 4 years and 9 months
measure: Phase 1 and 2: Time To Response (TTR)
timeFrame: Up to 4 years and 9 months
measure: Phase 2: Duration of Complete Response (CR)/Complete Remission With Partial Hematologic Recovery (CRh)
timeFrame: Up to 4 years and 9 months
measure: Phase 2: Time To CR/CRh
timeFrame: Up to 4 years and 9 months
measure: Phase 2: Event-free survival (EFS)
timeFrame: Up to 4 years and 9 months
measure: Phase 2: Overall survival (OS)
timeFrame: Up to 4 years and 9 months
measure: Phase 2: Measurable Residual Disease (MRD) Negativity Among Participants Achieving CR/CRh/CRi
timeFrame: Up to 4 years and 9 months
measure: Phase 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 4 years and 9 months
measure: Phase 2: Number of Participants Reporting Transfusion Independence
timeFrame: Up to 4 years and 9 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Start Midwest
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Portland
country: United States
facility: Oregon Health And Science University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Maine Health
state: Rhode Island
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: San Antonio
country: United States
facility: San Antonio Methodist TX Transplant Physicians Group
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Milwaukee
country: United States
facility: Medical College of WI at Froedtert
state: Wisconsin
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Southport
country: Australia
facility: Gold Coast University Hospital
city: Brasilia
country: Brazil
facility: Instituto D Or de Pesquisa e Ensino
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
city: Sao Paulo
country: Brazil
facility: Instituto D Or de Pesquisa e Ensino IDOR
city: Vancouver
country: Canada
facility: Vancouver Coastal Health
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve Rosemont
state: Quebec
city: Beijing
country: China
facility: Peking University First Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital Si Chuan University
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical Hospital
city: Hang Zhou
country: China
facility: First Affiliated Hospital Medical School of Zhejiang University
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
city: Nanchang
country: China
facility: The First Affiliated Hospital of NanChang University
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
city: Tian Jin
country: China
facility: Institute of Hematology and Blood Diseases Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College of Huazhong University of Science and Technology
city: Zheng Zhou Shi
country: China
facility: Henan Cancer Hospital
city: Besancon
country: France
facility: Hopital Jean Minjoz
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes Cedex 1
country: France
facility: CHU de Nantes hotel Dieu
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hopital trousseau- APHP
city: Pessac
country: France
facility: Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie
city: Pierre Benite
country: France
facility: CHU Lyon Sud
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe ICANS
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse Oncopole
city: Tours cedex
country: France
facility: CHU Bretonneau
city: Vandoeuvre les Nancy
country: France
facility: CHRU Nancy Brabois
city: Villejuif
country: France
facility: Gustave Roussy
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospita Ein Kerem
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Kobe City
country: Japan
facility: Kobe City Medical Center General Hospital
city: Maebashi
country: Japan
facility: Gunmaken Saiseikai Maebashi Hospital
city: Nagoya
country: Japan
facility: Nagoya University Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Tokyo
country: Japan
facility: NTT Medical Center Tokyo
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Yoshida
country: Japan
facility: University of Fukui Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust
city: Oxfordshire
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: