A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia (cAMeLot-1)

Official title

A Phase 1/2, First-in-Human Study of the Menin-KMT2A (MLL1) Inhibitor Bleximenib in Participants With Acute Leukemia (cAMeLot-1)

Overview

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.

Interventions

• Drug Bleximenib
  Bleximenib is administered orally.

Primary outcome measures

• Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [Time frame: Up to 4 years and 9 months]
• Phase 1: Number of Participants with AEs by Severity [Time frame: Up to 4 years and 9 months]
• Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT) [Time frame: Up to 28 days Cycle 1]
• Phase 2: Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh) [Time frame: Up to 4 years and 9 months]

Secondary outcome measures (11)

• Phase 1 and 2: Plasma Concentration of Bleximenib [Time frame: Up to 4 years and 9 months]
• Phase 1 and 2: Overall Response Rate (ORR) [Time frame: Up to 4 years and 9 months]
• Phase 1: Duration of Response (DOR) [Time frame: Up to 4 years and 9 months]
• Phase 1 and 2: Time To Response (TTR) [Time frame: Up to 4 years and 9 months]
• Phase 2: Duration of Complete Response (CR)/Complete Remission With Partial Hematologic Recovery (CRh) [Time frame: Up to 4 years and 9 months]
• Phase 2: Time To CR/CRh [Time frame: Up to 4 years and 9 months]
• Phase 2: Event-free survival (EFS) [Time frame: Up to 4 years and 9 months]
• Phase 2: Overall survival (OS) [Time frame: Up to 4 years and 9 months]
• Phase 2: Measurable Residual Disease (MRD) Negativity Among Participants Achieving CR/CRh/CRi [Time frame: Up to 4 years and 9 months]
• Phase 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Up to 4 years and 9 months]
• Phase 2: Number of Participants Reporting Transfusion Independence [Time frame: Up to 4 years and 9 months]

Eligibility criteria

Inclusion criteria

Phase 1:

• Age 2 years to less than (<) 18 years of age (pediatric cohort only), all other cohorts 18 years and above
• Relapsed or refractory (R/R) acute leukemia and has exhausted, or is ineligible for, available therapeutic options
• 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 <= 20\*10\^9/liter (L) and (b) renal function; For adult participants, estimated or measured glomerular filtration rate >= 30 milliliter per minute (mL/min) per four variable MDRD equation. For pediatric participants an estimated or measured glomerular filtration rate >=40 mL/min per the CKiD (Chronic Kidney Disease in Children) Schwartz formula
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Pediatric 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
• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 26 centers

• City of Hope — Duarte
• University of California Irvine Medical Center — Orange
• University of California San Francisco — San Francisco
• UCSF Benioff Children's Hospital — San Francisco
• University of Chicago — Chicago
• St Francis Hospital & Health Centers Indiana Blood and Marrow Transplantation — Indianapolis
• Norton Cancer Institute — Louisville
• Massachusetts General Hospital — Boston
• … and 18 more centers

France · 13 centers

• Hopital Jean Minjoz — Besançon
• Institut Paoli Calmettes — Marseille
• CHU de Nantes hotel Dieu — Nantes
• Hopital Saint Louis — Paris
• Hopital trousseau- APHP — Paris
• Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Mag — Pessac
• CHU Lyon Sud — Pierre-Bénite
• Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre — Strasbourg
• … and 5 more centers

China · 12 centers

• Peking University First Hospital — Beijing
• The First Hospital of Jilin University — Changchun
• West China Hospital Si Chuan University — Chengdu
• Nanfang Hospital of Southern Medical Hospital — Guangzhou
• First Affiliated Hospital Medical School of Zhejiang University — Hangzhou
• Qilu Hospital of Shandong University — Jinan
• The First Affiliated Hospital of NanChang University — Nanchang
• Zhongda Hospital Southeast University — Nanjing
• … and 4 more centers

Japan · 11 centers

• Kyushu University Hospital — Fukuoka
• Fukushima Medical University Hospital — Fukushima
• Kanazawa University Hospital — Kanazawa
• National Cancer Center Hospital East — Kashiwa
• Kobe City Medical Center General Hospital — Kobe
• Gunmaken Saiseikai Maebashi Hospital — Maebashi
• Nagoya University Hospital — Nagoya
• Hokkaido University Hospital — Sapporo
• … and 3 more centers

Spain · 9 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 8 centers

Center list to be confirmed — check the primary protocol.

Brazil · 6 centers

• Instituto D Or de Pesquisa e Ensino — Brasília
• Liga Norte Riograndense Contra O Cancer — Natal
• Ministerio da Saude Instituto Nacional do Cancer — Rio de Janeiro
• Fundacao Faculdade de Medicina Instituto do Cancer do Estado de Sao Paulo — São Paulo
• Instituto D Or de Pesquisa e Ensino IDOR — São Paulo
• Fundacao Antonio Prudente A C Camargo Cancer Center — São Paulo

Israel · 4 centers

• Carmel Medical Center — Haifa
• Hadassah University Hospita Ein Kerem — Jerusalem
• Sheba Medical Center — Ramat Gan
• Tel Aviv Sourasky Medical Center — Tel Aviv

Australia · 3 centers

• Monash Medical Centre — Clayton
• Royal Perth Hospital — Perth
• Gold Coast University Hospital — Southport

Canada · 3 centers

• Vancouver Coastal Health — Vancouver
• Princess Margaret Cancer Centre University Health Network — Toronto
• Hopital Maisonneuve Rosemont — Montreal

South Korea · 3 centers

• Seoul National University Hospital — Seoul
• … and 2 more centers

Taiwan · 3 centers

Center list to be confirmed — check the primary protocol.

Belgium · 1 center

• Ghent University Hospital — Ghent

Publications

• Kwon MC, Thuring JW, Querolle O, Dai X, Verhulst T, Pande V, Marien A, Goffin D, Wenge DV, Yue H, Cutler JA, Jin C, Perner F, Hogeling SM, Shaffer PL, Jacobs F, Vinken P, Cai W, Keersmaekers V, Eyassu F, Bhogal B, Verstraeten K, El Ashkar S, Perry JA, Jayaguru P, Barreyro L, Kuchnio A, Darville N, Krosky D, Urbanietz G, Verbist B, Edwards JP, Cowley GS, Kirkpatrick R, Steele R, Ferrante L, Guttke PMID 38905635

Identifiers

NCT: NCT04811560 · CR108998 · 75276617ALE1001 · 2023-506581-31-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗