Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Ongoing, recruitment ended
Participants planned
146
Countries
4
Sites
22
Acute Myeloid Leukemia
1. Dose Selection: Determine the recommended RP2D candidate(s) of bleximenib in combination with AML-directed therapies 2. Dose Expansion: Further evaluate safety and tolerability of bleximenib in combination with AML-directed therapies at the RP2D(s)
Key facts
- Sponsor
- Janssen - Cilag International
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 21 Jul 2022 → ongoing
- Decision date (initial)
- 2024-03-18
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2023-506582-58-00
- EudraCT number
- 2021-003999-14
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Dose response, Others, Efficacy, Pharmacokinetic, Pharmacodynamic, Safety
1. Dose Selection: Determine the recommended RP2D candidate(s) of bleximenib in combination with AML-directed therapies
2. Dose Expansion: Further evaluate safety and tolerability of bleximenib in combination with AML-directed therapies at the RP2D(s)
Conditions and MedDRA coding
Acute Myeloid Leukemia
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10000886 | Acute myeloid leukemia | 10029104 |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- Yes
- IPD plan description
- The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/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
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Diagnosis of AML according to World Health Organization (WHO) criteria: a) De novo or secondary AML; b) relapsed /refractory (Arm A only); c) harboring NPM1, KMT2A, NUP98, or NUP214 alterations
- Pretreatment clinical laboratory values meeting the following criteria -listed below: White blood cell (WBC) count: less than or equal to <=25 x 10^9 per liter (/L), adequate liver and renal function
- ECOG performance status grade of 0, 1 or 2
- 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 LAR) 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 6
- 1. Acute promyelocytic leukemia diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic leukemia according to WHO 2016 criteria
- 2. Leukemic involvement of the central nervous system
- 3. Recipient of solid organ transplant
- 5. 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
- 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- 1. Incidence and severity of AEs, including DLTs
- 2. Incidence and severity of Aes
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 23
PRD11370369 · Product
- Active substance
- Bleximenib
- Substance synonyms
- N-ethyl-5-fluoro-N-isopropyl-2-[[5-(2-[(3R)-6-[(2-methoxyethyl)(methyl)amino]-2-methylhexan-3-yl]-2,6-diazaspiro[3.4]octan-6-yl)-1,2,4-triazin-6-yl]oxy]benzamide, JNJ-75276617
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
PRD11370367 · Product
- Active substance
- Bleximenib
- Substance synonyms
- N-ethyl-5-fluoro-N-isopropyl-2-[[5-(2-[(3R)-6-[(2-methoxyethyl)(methyl)amino]-2-methylhexan-3-yl]-2,6-diazaspiro[3.4]octan-6-yl)-1,2,4-triazin-6-yl]oxy]benzamide, JNJ-75276617
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
PRD11370368 · Product
- Active substance
- Bleximenib
- Substance synonyms
- N-ethyl-5-fluoro-N-isopropyl-2-[[5-(2-[(3R)-6-[(2-methoxyethyl)(methyl)amino]-2-methylhexan-3-yl]-2,6-diazaspiro[3.4]octan-6-yl)-1,2,4-triazin-6-yl]oxy]benzamide, JNJ-75276617
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
PRD10622891 · Product
- Active substance
- JNJ-75276617
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
PRD11825465 · Product
- Active substance
- Bleximenib
- Substance synonyms
- N-ethyl-5-fluoro-N-isopropyl-2-[[5-(2-[(3R)-6-[(2-methoxyethyl)(methyl)amino]-2-methylhexan-3-yl]-2,6-diazaspiro[3.4]octan-6-yl)-1,2,4-triazin-6-yl]oxy]benzamide, JNJ-75276617
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
PRD10820462 · Product
- Active substance
- JNJ-75276617
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
PRD10622893 · Product
- Active substance
- JNJ-75276617
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
PRD10622892 · Product
- Active substance
- JNJ-75276617
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
PRD10622887 · Product
- Active substance
- JNJ-75276617
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
PRD10622886 · Product
- Active substance
- JNJ-75276617
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
Cytarabine 100 mg/ml Solution for Injection or Infusion
PRD1957509 · Product
- Active substance
- Cytarabine
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Authorised
- ATC code
- L01BC01 — CYTARABINE
- Marketing authorisation
- PL 20075/0121
- MA holder
- ACCORD HEALTHCARE LIMITED
- MA country
- United Kingdom
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cytarabine 100 mg/ml Solution for Injection or Infusion
PRD1957511 · Product
- Active substance
- Cytarabine
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Authorised
- ATC code
- L01BC01 — CYTARABINE
- Marketing authorisation
- PL 20075/0121
- MA holder
- ACCORD HEALTHCARE LIMITED
- MA country
- United Kingdom
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Idarubicin Hikma 1 mg/ml Injektionslösung
PRD8175088 · Product
- Active substance
- Idarubicin Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Authorised
- ATC code
- L01DB06 — IDARUBICIN
- Marketing authorisation
- 2204857.00.00
- MA holder
- HIKMA PHARMA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Daunoblastin® 20 mg Pulver zur Herstellung einer Infusions- oder Injektionslösung
PRD4259174 · Product
- Active substance
- Daunorubicin Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Authorised
- ATC code
- L01DB02 — DAUNORUBICIN
- Marketing authorisation
- 69540.00.00
- MA holder
- PFIZER PHARMA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
CYTARABINE ACCORD 100 mg/ml, solution injectable ou pour perfusion
PRD1957478 · Product
- Active substance
- Cytarabine
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Authorised
- ATC code
- L01BC01 — CYTARABINE
- Marketing authorisation
- 34009 585 319 6 5
- MA holder
- ACCORD HEALTHCARE FRANCE SAS
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD11073029 · Product
- Active substance
- Idarubicin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
Citarabina Hikma 500mg/5mL Soluzione Iniettabile
PRD5259314 · Product
- Active substance
- Cytarabine
- Substance synonyms
- ARA-C, CYTOSINE ARABINOSIDE
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Authorised
- ATC code
- L01BC01 — CYTARABINE
- Marketing authorisation
- 034164 032
- MA holder
- HIKMA FARMACÊUTICA (PORTUGAL), S.A.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Citarabina Hikma 2 g/20mL Soluzione Iniettabile
PRD5259317 · Product
- Active substance
- Cytarabine
- Substance synonyms
- ARA-C, CYTOSINE ARABINOSIDE
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Authorisation status
- Authorised
- ATC code
- L01BC01 — CYTARABINE
- Marketing authorisation
- 034164 069
- MA holder
- HIKMA FARMACÊUTICA (PORTUGAL), S.A.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD11071407 · Product
- Active substance
- Azacitidine
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
Venclyxto 50 mg film-coated tablets
PRD6353830 · Product
- Active substance
- Venetoclax
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Authorised
- ATC code
- L01XX52 — -
- Marketing authorisation
- EU/1/16/1138/004
- MA holder
- ABBVIE DEUTSCHLAND GMBH & CO. KG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Venclyxto 100 mg film-coated tablets
PRD6353842 · Product
- Active substance
- Venetoclax
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Authorised
- ATC code
- L01XX52 — -
- Marketing authorisation
- EU/1/16/1138/007
- MA holder
- ABBVIE DEUTSCHLAND GMBH & CO. KG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Venclyxto 100 mg film-coated tablets
PRD6353834 · Product
- Active substance
- Venetoclax
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Authorised
- ATC code
- L01XX52 — -
- Marketing authorisation
- EU/1/16/1138/005
- MA holder
- ABBVIE DEUTSCHLAND GMBH & CO. KG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD11071408 · Product
- Active substance
- Azacitidine
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Authorisation status
- Not Authorised
- MA holder
- JANSSEN-CILAG INTERNATIONAL N.V.
- Paediatric formulation
- No
- Orphan designation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Janssen - Cilag International
- Sponsor organisation
- Janssen - Cilag International
- Address
- Turnhoutseweg 30
- City
- Beerse
- Postcode
- 2340
- Country
- Belgium
Scientific contact point
- Organisation
- Janssen - Cilag International
- Contact name
- CTIS Point of Contact
Public contact point
- Organisation
- Janssen - Cilag International
- Contact name
- CTIS Point of Contact
Third parties 11
| Organisation | City, country | Duties |
|---|---|---|
| 4g Clinical LLC ORG-100042775
|
Wellesley, United States | Interactive response technologies (IRT) |
| IQVIA Limited ORG-100008655
|
Reading, United Kingdom | Data management |
| Pharmaceutical Research Associates Group B.V. ORG-100006268
|
Assen, Netherlands | Laboratory analysis |
| Ancillare LP ORG-100044089
|
Horsham, United States | Other |
| Ppd Inc. ORG-100018960
|
Middleton, United States | Laboratory analysis |
| Labcorp Central Laboratory Services LP ORG-100032236
|
Indianapolis, United States | Other |
| Hematogenix Laboratory Services Limited ORG-100047188
|
Cheadle, United Kingdom | Other, Laboratory analysis |
| Eresearchtechnology Inc. ORG-100013039
|
Philadelphia, United States | Code 13, Other |
| Hematogenix ORG-100047219
|
Cyberjaya, Malaysia | Other, Laboratory analysis |
| Parexel International (IRL) Limited ORG-100022780
|
Dublin 2, Ireland | Data management |
| eResearchTechnology GmbH ORG-100044103
|
Estenfeld, Germany | Code 13, Other |
Locations
4 EU/EEA countries · 22 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruitment ended | 18 | 5 |
| Germany | Ongoing, recruitment ended | 25 | 7 |
| Italy | Ongoing, recruitment ended | 13 | 4 |
| Spain | Ongoing, recruitment ended | 30 | 6 |
| Rest of world
United Kingdom, Australia, United States
|
— | 60 | — |
Investigational sites
Centre Hospitalier Universitaire De Rennes
Hopital Pontchaillou - Hématologie, 2 Rue Henri Le Guilloux, 35000, Rennes
Assistance Publique Hopitaux De Paris
Pediatric hematology and oncology, 26 Avenue Du Docteur Arnold Netter, 75012, Paris
Institut Universitaire Du Cancer Toulouse-Oncopole
Hematology, 1 Avenue Irene Joliot Curie, 31100, Toulouse
Institut Paoli-Calmettes
Hématologie, 232 Boulevard De Sainte Marguerite, Bp 156, Marseille
Centre Hospitalier Regional Universitaire De Tours
Hematology, 2 Boulevard Tonnelle, 37044, Tours Cedex 9
Universitaet Leipzig
Zentrum fuer Frauen- u. Kindermedizin, Abt. fuer paediatrische Onkologie, Haematol. u. Haemostaseol, Liebigstrasse 22, Zentrum-Suedost, Leipzig
Universitaetsklinikum Heidelberg AöR
Medizinischen Klinik V Haematologie, Onkologie und Rheumatologie, Im Neuenheimer Feld 410, Neuenheim, Heidelberg
Universitaetsklinikum Ulm AöR
Klinik für Innere Medizin III Zentrum für Innere Medizin, Albert-Einstein-Allee 23, Eselsberg, Ulm
Charite Universitaetsmedizin Berlin KöR
Medizinische Klinik m.S. Haematologie, Onkologie und Tumorimmunologie, Augustenburger Platz 1, Wedding, Berlin
Universitaet Leipzig
Med. Klinik-Poliklinik I-Hamatologie-Zelltherapie, Hamostaseologie Early Clinical Trials Unit, Liebigstrasse 22, Zentrum-Suedost, Leipzig
Universitaetsklinikum Ulm AöR
Klinik für Kinder- und Jugendmedizin; Paediatrische Onkologie, Eythstrasse 24, Mitte, Ulm
Technische Universitat Dresden
Medizinische Klinik und Poliklinik I. Haematologie, Zelltherapie und medizinische Onkologie, Fetscherstrasse 74, Johannstadt-Nord, Dresden
Humanitas Research Hospital
U.O. di Oncologia Medica ed Ematologia, Via Alessandro Manzoni 56, 20089, Rozzano
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Struttura Semplice Dipartimentale (SSD) Ematologia, Via Piero Maroncelli 40, 47014, Meldola
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Unità Operativa di Ematologia – Pad. 8, Via Pietro Albertoni 15, 40138, Bologna
Azienda Ospedaliera Ospedale Niguarda Ca Granda
Struttura Complessa di Ematologia, Piazza Dell'ospedale Maggiore 3, 20162, Milan
Hospital De La Santa Creu I Sant Pau
Hematology, Carrer De San Quinti 89, 08041, Barcelona
Hospital Universitario Fundacion Jimenez Diaz
Hematology, Avenida De Los Reyes Catolicos 2, 28040, Madrid
Hospital Universitari Vall D Hebron
Hematology, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona
Hospital Clinic De Barcelona
Hematology, Calle Villarroel 170, 08036, Barcelona
Hospital Infantil Universitario Nino Jesus
Hematology, Avenida Menendez Pelayo 65, 28009, Madrid
Clinica Universidad De Navarra
Hematology, Avenue Pio XII 36, 31008, Pamplona
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2022-07-21 | 2022-07-21 | 2026-01-14 | ||
| Germany | 2022-09-15 | 2022-09-15 | 2026-01-14 | ||
| Italy | 2022-12-01 | 2022-12-01 | 2026-01-14 | ||
| Spain | 2022-08-04 | 2022-08-04 | 2026-01-14 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-02-01 | Spain | Acceptable 2024-03-11
|
2024-03-18 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-08-12 | Spain | Acceptable 2024-10-10
|
2024-10-10 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-10-22 | Spain | Acceptable 2024-10-10
|
2024-10-22 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-02-04 | Spain | Acceptable 2025-05-05
|
2025-05-06 |
| 5 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-07-10 | Spain | Acceptable 2025-09-29
|
2025-09-30 |