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JOURNAL ONKOLOGIE – STUDIE

A Study of JNJ-75276617 in Combination With Acute Myeloid Leukemia (AML) Directed Therapies

Rekrutierend

NCT-Nummer:
NCT05453903

Studienbeginn:
Oktober 2022

Letztes Update:
24.04.2024

Wirkstoff:
JNJ-75276617, Venetoclax (VEN), Azacitidine (AZA), Cytarabine, Daunorubicin or idarubicin

Indikation (Clinical Trials):
Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Janssen Research & Development, LLC

Collaborator:
-

Studienleiter

Janssen Research & Development, LLC Clinical Trial
Study Director
Janssen Research & Development, LLC

Kontakt

Studienlocations
(3 von 29)

Charite Universitatsmedizin Berlin
13353 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Universitatsklinikum Carl Gustav Carus Dresden
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
Universitaetsklinikum Heidelberg
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Universitaetsklinikum Leipzig
04103 Leipzig
(Sachsen)
GermanyRekrutierend» Google-Maps
Universitatsklinikum Ulm
89081 Ulm
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
The University of Alabama at Birmingham
35233 Birmingham
United StatesRekrutierend» Google-Maps
Massachusetts General Hospital
02114 Boston
United StatesRekrutierend» Google-Maps
Albert Einstein College Of Medicine
10461 New York
United StatesRekrutierend» Google-Maps
Novant Health Forsyth Medical Center
27103 Winston-Salem
United StatesRekrutierend» Google-Maps
Peter MacCallum Cancer Centre
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Institut Paoli Calmettes
13273 Marseille Cedex 9
FranceRekrutierend» Google-Maps
Institut Universitaire du Cancer Toulouse Oncopole
31100 Toulouse Cedex 9
FranceRekrutierend» Google-Maps
CHU de Tours - Hôpital de Bretonneau
37044 Tours
FranceRekrutierend» Google-Maps
Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
40138 Bologna
ItalyRekrutierend» Google-Maps
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
47014 Meldola
ItalyRekrutierend» Google-Maps
ASST Grande Ospedale Metropolitano Niguarda
20162 Milano
ItalyRekrutierend» Google-Maps
IRCCS Istituto Clinico Humanitas
20089 Rozzano
ItalyRekrutierend» Google-Maps
Hosp. de La Santa Creu I Sant Pau
08025 Barcelona
SpainRekrutierend» Google-Maps
University College London Hospitals NHSFT
NW1 2PG London
United KingdomRekrutierend» Google-Maps
Christie Hospital NHS Trust
M20 4BX Manchester
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

AML is a heterogenous disease characterized by uncontrolled clonal expansion of hematopoietic

progenitor cells (myeloid blasts) in the peripheral blood, bone marrow and other tissues and

is the most common type of acute leukemia in adults. JNJ-75276617 is an orally bioavailable,

potent, and selective protein-protein interaction inhibitor of the binding between

histone-lysine N-methyltransferase 2A ([KMT2A], also called mixed-lineage leukemia 1 [MLL1];

wild-type and fusion) and menin, with activity in leukemic cell lines and primary leukemia

patient or patient-derived samples with either KMT2A alterations including gene

rearrangements (KMT2A-r), duplications, and amplification, or nucleophosmin 1 gene (NPM1)

alterations. The aim of this study is to determine the RP2D(s), safety, pharmacokinetic,

pharmacodynamic and preliminary clinical activity of JNJ-75276617 in combination with AML

directed therapies for adult participants with relapsed/refractory or newly diagnosed AML

with NPM1 or KMT2A gene alterations and will include dose selection and subsequent

combination specific dose expansion. The total study duration will be up to 2 years. Safety

evaluations include adverse events (AE) monitoring, clinical laboratory tests,

electrocardiograms (ECGs), vital sign measurements, physical examination findings, and

eastern cooperative oncology group (ECOG) performance status score.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- 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

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 woman 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 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 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 (less

than [<] 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 (uncomplicated Grade less than or equal to [≤]2 deep vein thrombosis is not

considered exclusionary);(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

Studien-Rationale

Primary outcome:

1. Number of Participants with Adverse Events (AEs) (Time Frame - Up to 3 Years 3 months):
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.

2. Number of Participants with Adverse Events (AEs) by Severity (Time Frame - Up to 3 Years 3 months):
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.

3. Number of Participants with Dose-limiting Toxicity (DLT) (Time Frame - End of Cycle 1 (28 days)):
Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined per protocol as any of the following: non-hematologic toxicity, or hematologic toxicity.

Secondary outcome:

1. Plasma Concentration of JNJ- 75276617 (Time Frame - Up to 3 Years 3 months):
Plasma samples will be analyzed to determine concentrations of JNJ-75276617 using a validated, specific, and sensitive method.

2. Number of Participants with Depletion of Leukemic Blasts (Time Frame - Up to 3 Years 3 months):
Number of participants with depletion of leukemic blasts will be reported.

3. Number of Participants with Differentiation of Leukemic Blasts (Time Frame - Up to 3 Years 3 months):
Number of participants with differentiation of leukemic blasts will be reported.

4. Changes in Expression of Menin-histone-lysine N-methyltransferase 2A (KMT2A) Target Genes (Time Frame - Up to 3 Years 3 months):
Changes in expression of menin-KMT2A target genes will be reported.

5. Percentage of Participants who Achieve Complete Remission (CR) (Time Frame - Up to 3 Years 3 months):
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 and blasts with Auer rods; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (>=) 1.0 x 109/Liter (1,000/microliter [μL] ); Platelet count >= 100 x 109/L (100,000/μL).

6. Percentage of Participants who Achieve Complete Remission with Partial Hematologic Recovery (CRh) (Time Frame - Up to 3 Years 3 months):
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 x 109/L (500/μL) and platelet count >50 x 109/L (50,000/μL).

7. Percentage of Participants who Achieve Complete Remission with Incomplete Hematologic Recovery (CRi) (Time Frame - Up to 3 Years 3 months):
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 x 109/L [1,000/μL]) or thrombocytopenia (<100 x 109/L [100,000/μL]).

8. Percentage of Participants who Achieved Overall Response (Time Frame - Up to 3 Years 3 months):
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.

9. Duration of response (Time Frame - Up to 3 Years 3 months):
Duration of response is defined as time from achieving first response of CR, CRh, CRi or overall response to hematologic relapse or death of any cause.

10. Time to Response (Time Frame - Up to 3 Years 3 months):
Time to response is defined as time from first dose to achieving the first response of CR, CRh, CRi or overall response.

Studien-Arme

  • Experimental: Arm A: Relapsed/Refractory Setting
    Participants with relapsed/refractory AML harboring either NPM1 or KMT2A alterations will receive JNJ-75276617 in combination with either venetoclax (VEN) (Cohort A1: JNJ75276617+VEN) or azacitidine (AZA) (Cohort A2: JNJ-75276617+AZA) or VEN+AZA (Cohort A3: JNJ-75276617+VEN+AZA) to select the recommended phase 2 dose (RP2D) of JNJ-75276617 in combination with VEN, AZA or VEN+AZA (dose selection). In dose expansion portion of the study, participants will receive JNJ-75276617 in combination with AML directed therapies at the RP2D(s).
  • Experimental: Arm B: Newly Diagnosed Chemotherapy Ineligible Setting
    Participants will receive JNJ-75276617 in combination with VEN+AZA as frontline chemo therapy for newly diagnosed AML participants harboring either KMT2A or NPM1 alterations who are greater than or equal to (>=)18 years of age to less than (<) 75 years of age with comorbidities that preclude the use of intensive induction chemotherapy.
  • Experimental: Arm C: Newly Diagnosed Chemotherapy Eligible Setting
    Participants will receive combination of JNJ-75276617 with cytarabine+daunorubicin or idarubicin chemotherapy as frontline treatment regimen for participants >=18 to <75 years of age with AML harboring either NPM1 or KMT2A alterations and eligible for intensive chemotherapy.

Geprüfte Regime

  • JNJ-75276617:
    Participants will receive JNJ-75276617.
  • Venetoclax (VEN):
    Participants will receive VEN.
  • Azacitidine (AZA):
    Participants will receive AZA.
  • Cytarabine:
    Participants will receive cytarabine
  • Daunorubicin or Idarubicin:
    Participants will receive daunorubicin or idarubicin

Quelle: ClinicalTrials.gov


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