En studie av JNJ-75276617 i kombination med akut myeloid leukemi (AML) riktade terapier
En fas 1b-studie av JNJ-75276617 i kombination med AML-inriktade terapier för deltagare med akut myeloid leukemi som innehåller KMT2A- eller NPM1-förändringar
The purpose of this study is to determine the recommended Phase 2 dose (RP2D) candidate(s) of bleximenib in combination with AML directed therapies (dose selection) and further to evaluate safety and tolerability of bleximenib in combination with AML directed therapies at the RP2D(s) (dose expansion).
Studieöversikt
Status
Betingelser
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 1
Kontakter och platser
Studieorter
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Clayton, Australien, 3168
- Monash Medical Centre
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Melbourne, Australien, 3000
- Peter MacCallum Cancer Centre
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Westmead, Australien, 2145
- Westmead Hospital
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Marseille, Frankrike, 13273
- Institut Paoli Calmettes
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Rennes, Frankrike, 35033
- Chu Rennes Hopital Pontchaillou
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Toulouse, Frankrike, 31100
- Institut Universitaire du Cancer Toulouse Oncopole
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Tours, Frankrike, 37044
- CHU de Tours - Hôpital de Bretonneau
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Alabama
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Birmingham, Alabama, Förenta staterna, 35233
- The University of Alabama at Birmingham
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California
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Duarte, California, Förenta staterna, 91010
- City of Hope
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Massachusetts
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Boston, Massachusetts, Förenta staterna, 02114
- Massachusetts General Hospital
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New York
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New York, New York, Förenta staterna, 10461
- Albert Einstein College Of Medicine
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North Carolina
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Charlotte, North Carolina, Förenta staterna, 28204
- Novant Health
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Winston-Salem, North Carolina, Förenta staterna, 27103
- Novant Health Forsyth Medical Center
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Texas
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Houston, Texas, Förenta staterna, 77030
- MD Anderson
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Bologna, Italien, 40138
- Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
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Meldola, Italien, 47014
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
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Milan, Italien, 20162
- ASST Grande Ospedale Metropolitano Niguarda
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Rozzano, Italien, 20089
- IRCCS Istituto Clinico Humanitas
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Ontario
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Toronto, Ontario, Kanada, M5G 1Z5
- Princess Margaret Cancer Centre University Health Network
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Barcelona, Spanien, 08041
- Hosp. de La Santa Creu I Sant Pau
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Barcelona, Spanien, 08036
- Hosp Clinic de Barcelona
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Barcelona, Spanien, 8035
- Hosp Univ Vall D Hebron
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Madrid, Spanien, 28040
- Hosp Univ Fund Jimenez Diaz
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Pamplona, Spanien, 31008
- Clinica Univ. de Navarra
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London, Storbritannien, NW1 2PG
- University College London Hospitals NHSFT
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Manchester, Storbritannien, M20 4BX
- Christie Hospital NHS Trust
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Oxfordshire, Storbritannien, OX3 7LE
- Oxford University Hospitals NHS Trust
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Berlin, Tyskland, 13353
- Charite Universitaetsmedizin Berlin
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Dresden, Tyskland, 01307
- Universitatsklinikum Carl Gustav Carus Dresden
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Heidelberg, Tyskland, 69120
- Universitaetsklinikum Heidelberg
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Leipzig, Tyskland, 04103
- Universitaetsklinikum Leipzig
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Ulm, Tyskland, 89081
- Universitatsklinikum Ulm
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Adolescent participants (defined as greater than or equal to [>=] 12 and less than [<] 18 years of age) are only eligible for the relapsed/refractory (R/R) cohort (Arm A, cohort A4)
- Diagnosis of AML according to World Health Organization (WHO) criteria: a) De novo or secondary AML; b) relapsed/refractory (Arm A only); c) harboring KMT2A, NPM1, NUP98, or NUP214 alterations; d) Participants may receive emergency leukapheresis and/or cytarabine as cytoreductive therapy according to local practice guidelines
- Pretreatment clinical laboratory values meeting the following criteria -listed below: White blood cell (WBC) count: less than or equal to (<=) 25*10^9 per liter (/L), adequate liver and renal function
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Adolescent 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
- Must sign an informed consent form (ICF) indicating participant (or their legally authorized representative) understands the purpose of the study and procedures required for the study and is willing to participate in the study
- Willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion Criteria:
- Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic leukemia according to WHO 2016 criteria
- Leukemic involvement of the central nervous system
- Recipient of solid organ transplant
- Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes or that was diagnosed within 6 months prior to the first dose of study treatment including, but not limited to: (a) Myocardial infarction; (b) Severe or unstable angina; (c) Clinically significant cardiac arrhythmias, including bradycardia (<50 beats per minute); (d) Uncontrolled (persistent) hypertension: (example, blood pressure greater than [>] 140/90 millimeters of mercury [mm Hg]; (e) Acute neurologic events such as stroke or transient ischemic attack, intracranial or subarachnoid hemorrhage, intracranial trauma; (f) Venous thromboembolic events (example, pulmonary embolism) within 1 month prior to the first dose of study treatment ;(g) Congestive heart failure (NYHA class III to IV); (h) Pericarditis or clinically significant pericardial effusion; (i) Myocarditis; (j) Endocarditis (k) Clinically significant hypokalemia, hypomagnesemia, hypocalcemia (corrected for hypoalbuminemia)
- Any toxicity (except for alopecia, stable peripheral neuropathy, thrombocytopenia, neutropenia, anemia) from previous anticancer therapy that has not resolved to baseline or to grade 1 or less
- Pulmonary compromise that requires the need for supplemental oxygen use to maintain adequate oxygenation
- Participants with diagnosis of Fanconi anemia, Kostmann syndrome, Shwachman diamond syndrome, or any other known bone marrow failure syndrome
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Sekventiell tilldelning
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: Arm A: Relapsed/Refractory Setting
Participants with relapsed/refractory AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations will receive bleximenib in combination with either venetoclax (VEN) (Cohort A1: bleximenib+VEN) or azacitidine (AZA) (Cohort A2: bleximenib +AZA) or VEN+AZA (Cohort A3: bleximenib+VEN+AZA) or VEN + AZA (Cohort A4: bleximenib + VEN + AZA) in adolescent participants aged greater than or equal to (>=) 12 years and less than (<) 18 years of age, to select the recommended phase 2 dose (RP2D) of bleximenib in combination with VEN, AZA or VEN+AZA (dose selection). In dose expansion portion of the study, participants will receive bleximenib in combination with AML directed therapies at the RP2D(s). |
Participants will receive bleximenib.
Andra namn:
Participants will receive VEN. Participants will receive AZA. |
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Experimentell: Arm B: Newly Diagnosed Chemotherapy Ineligible Setting
Participants will receive bleximenib in combination with VEN+AZA as frontline chemo therapy for newly diagnosed AML participants harboring KMT2A, NPM1, NUP98, or NUP214 alterations who are >=75 years of age or >=18 years of age to <75 years of age with comorbidities that preclude the use of intensive induction chemotherapy. |
Participants will receive bleximenib.
Andra namn:
Participants will receive VEN. Participants will receive AZA. |
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Experimentell: Arm C: Newly Diagnosed Chemotherapy Eligible Setting
Participants will receive combination of bleximenib with cytarabine+daunorubicin or idarubicin chemotherapy as frontline treatment regimen for participants >= 18 to <75 years of age with AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations and eligible for intensive chemotherapy. |
Participants will receive bleximenib.
Andra namn:
Participants will receive cytarabine. Participants will receive daunorubicin or idarubicin. |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Number of Participants with Adverse Events (AEs)
Tidsram: Up to 3 Years 3 months
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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. |
Up to 3 Years 3 months
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Number of Participants with Adverse Events (AEs) by Severity
Tidsram: Up to 3 Years 3 months
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Number of Participants with AEs by severity will be reported. 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. |
Up to 3 Years 3 months
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Number of Participants with Dose-limiting Toxicity (DLT)
Tidsram: End of Cycle 1 (28 days)
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Number of participants with DLT will be reported according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. |
End of Cycle 1 (28 days)
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Plasma Concentration of Bleximenib
Tidsram: Up to 3 Years 3 months
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Plasma samples will be analyzed to determine concentrations of bleximenib using a validated, specific, and sensitive method. |
Up to 3 Years 3 months
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Number of Participants with Depletion of Leukemic Blasts
Tidsram: Up to 3 Years 3 months
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Number of participants with depletion of leukemic blasts will be reported. |
Up to 3 Years 3 months
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Percentage of Participants who Achieve Complete Remission (CR)
Tidsram: Up to 3 Years 3 months
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Percentage of participants who achieve complete Remission (CR) will be reported. CR is defined as Bone marrow blasts less than (<) 5 percent (%); Absence of circulating blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (>=) 1.0*10^9/Liter (L) (1,000/microliter [mcL]); Platelet count >= 100 * 10^9/L (100,000/mcL). |
Up to 3 Years 3 months
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Percentage of Participants who Achieve Complete Remission with Partial Hematologic Recovery (CRh)
Tidsram: Up to 3 Years 3 months
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Percentage of participants who achieve complete remission with partial hematologic recovery (CRh) will be reported. CRh is defined as All criteria of CR with both ANC >0.5 * 10^9/L (500/mcL) and platelet count >50 * 10^9/L (50,000/mcL). |
Up to 3 Years 3 months
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Percentage of Participants who Achieve Complete Remission with Incomplete Hematologic Recovery (CRi)
Tidsram: Up to 3 Years 3 months
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Percentage of participants who achieve complete remission with incomplete hematologic recovery (CRi) will be reported. CRi is defined as All CR criteria except for residual neutropenia (<1.0*10^9/L [1,000/mcL]) or thrombocytopenia (<100 * 10^9/L [100,000/mcL]). |
Up to 3 Years 3 months
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Percentage of Participants who Achieved Overall Response
Tidsram: Up to 3 Years 3 months
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Percentage of participants who achieve overall response will be reported. Overall response rate (ORR) is defined as the percentage of participants achieving CR, CRh, or CRi, morphologic leukemia-free state (MLFS) or partial remission (PR). |
Up to 3 Years 3 months
|
Samarbetspartners och utredare
Utredare
- Studierektor: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Publikationer och användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Neoplasmer
- Neoplasmer efter histologisk typ
- Hematologiska sjukdomar
- Leukemi, myeloid
- Leukemi
- Hemiska och lymfsjukdomar
- Leukemi, Myeloid, Akut
- Organiska kemikalier
- Heterocykliska föreningar, 1-ring
- Heterocykliska föreningar
- Nukleinsyror, nukleotider och nukleosider
- Kolväten
- Kolväten, cykliska
- Kolhydrater
- Polycykliska aromatiska kolväten
- Kolväten, aromatisk
- Polycykliska föreningar
- Glykosider
- Cytidin
- Pyrimidin nukleosider
- Pyrimidiner
- AZA -föreningar
- Nukleosider
- Ribonukleosider
- Arabinonukleosider
- Anthracykliner
- Naftakener
- Aminoglykosider
- Cytarabin
- Azacitidin
- Daunorubicin
- Idarubicin
- venetoklax
Andra studie-ID-nummer
- CR109124
- 2021-003999-14 (EudraCT-nummer)
- 75276617ALE1002 (Annan identifierare: Janssen Research & Development, LLC)
- 2023-506582-58-00 (Registeridentifierare: EUCT number)
- 2023 (U.S.S. NIH-anslag/kontrakt)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Läkemedels- och apparatinformation, studiedokument
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