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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Bleximenib
  Bleximenib is administered orally.

Первичные конечные точки

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

Вторичные конечные точки (11)

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

Критерии участия

Критерии включения

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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 26 центров

• 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
• … и ещё 18 центров

Франция · 13 центров

• 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
• … и ещё 5 центров

Китай · 12 центров

• Peking University First Hospital — Пекин
• The First Hospital of Jilin University — Changchun
• West China Hospital Si Chuan University — Чэнду
• Nanfang Hospital of Southern Medical Hospital — Гуанчжоу
• First Affiliated Hospital Medical School of Zhejiang University — Ханчжоу
• Qilu Hospital of Shandong University — Цзинань
• The First Affiliated Hospital of NanChang University — Nanchang
• Zhongda Hospital Southeast University — Нанкин
• … и ещё 4 центра

Япония · 11 центров

• 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
• … и ещё 3 центра

Испания · 9 центров

Список центров уточняется — проверьте первичный протокол.

Великобритания · 8 центров

Список центров уточняется — проверьте первичный протокол.

Бразилия · 6 центров

• 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

Израиль · 4 центра

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

Австралия · 3 центра

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

Канада · 3 центра

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

South Korea · 3 центра

• Seoul National University Hospital — Seoul
• … и ещё 2 центра

Тайвань · 3 центра

Список центров уточняется — проверьте первичный протокол.

Бельгия · 1 центр

• Ghent University Hospital — Ghent

Публикации

• 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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗