Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

Une étude du CA-4948 chez des patients atteints d'hémopathies malignes récidivantes ou réfractaires

1 octobre 2026 mis à jour par: Curis, Inc.

Lymphome TakeAim : un essai ouvert, d'escalade de dose et d'expansion de dose évaluant l'innocuité, la pharmacocinétique, la pharmacodynamique et l'activité clinique du CA-4948 administré par voie orale chez des patients atteints d'hémopathies malignes récidivantes ou réfractaires

This is a multi-center, open-label study to evaluate the safety, pharmacokinetics (PK), and anti-cancer activity of oral administration of emavusertib alone or in combination with ibrutinib in adult participants with relapsed or refractory (R/R) hematologic malignancies.

This trial will be completed in four parts. In Part A1, emavusertib will be evaluated first in a dose escalating monotherapy setting to establish the safety and tolerability (complete). In Part A2, emavusertib will be evaluated in combination with ibrutinib at 560 milligrams (mg) once daily (QD) or 420 mg QD as indicated by disease (Part A2 complete).

Part B will comprise 2 cohorts to assess safety and efficacy of emavusertib in combination with ibrutinib in participants with R/R primary central nervous system lymphoma (PCNSL) who have directly progressed on a bruton tyrosine kinase inhibitor (BTKi). In this part of the study, emavusertib will be dosed at 100 mg or 200 mg twice daily (BID) in combination with ibrutinib in 28-day treatment cycles.

Part C will comprise 3 treatment arms in the second-line setting to assess the efficacy and safety of emavusertib monotherapy, ibrutinib monotherapy, and emavusertib in combination with ibrutinib in participants with R/R PCNSL who are naïve to BTKi treatment. In this part of the study, eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will be randomized 1:1:1 to 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

152

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

  • Espagne
      • Barcelona, Espagne
        • Recrutement
        • University Hospital Vall d'Hebron
      • Madrid, Espagne
        • Recrutement
        • MD Anderson Cancer Center Madrid
      • Seville, Espagne
        • Recrutement
        • Hospital Universitario Virgen del Rocio
  • France
      • Bordeaux, France
        • Recrutement
        • Institut Bergonie
      • Marseille, France
        • Recrutement
        • Hopital de la Timone
      • Paris, France
        • Recrutement
        • Hospital Pitie Salpetriere
      • Paris, France
        • Recrutement
        • Institut Curie Hospital
  • Israël
      • Beersheba, Israël
        • Recrutement
        • Hematology Department Soroka UMC / Heanatology Department
      • Haifa, Israël
        • Recrutement
        • Rambam Medical Center
      • Jerusalem, Israël
        • Recrutement
        • Hadassah Medical Center / Ein-Carem
  • Italie
      • Cuneo, Italie
        • Recrutement
        • Università di Torino Croce e Carle
      • Florence, Italie
        • Recrutement
        • SODc Ematologia Azienda Ospedaliera Universitaria Careggi
      • Meldola, Italie
        • Recrutement
        • IRST - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      • Milan, Italie
        • Recrutement
        • IRCCS San Raffaele Scientific Institute
  • Pologne
      • Gdansk, Pologne
        • Recrutement
        • Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
      • Krakow, Pologne
        • Retiré
        • Oddzial Kliniczny Hematologii
      • Warsaw, Pologne
        • Recrutement
        • NarodowyInstytutu Onkologii im. Marii Sklodowskiej-Curie-Panstwowy Instytutu Badawczy
  • Tchéquie
      • Prague, Tchéquie
        • Recrutement
        • Všeobecná fakultní nemocnice v Praze
  • États-Unis
    • Arizona
      • Phoenix, Arizona, États-Unis, 85013
        • Recrutement
        • St. Joseph's Hospital and Medical Center
      • Phoenix, Arizona, États-Unis, 85054
        • Complété
        • Mayo Clinic
    • California
      • Duarte, California, États-Unis, 91010
        • Recrutement
        • City of Hope
      • Santa Monica, California, États-Unis, 90404
        • Recrutement
        • Providence St. John's Health Center
      • Santa Monica, California, États-Unis, 90404
        • Retiré
        • UCLA Department of Medicine - Hematology/Oncology
    • Connecticut
      • New Haven, Connecticut, États-Unis, 06510
        • Complété
        • Smilow Cancer Hospital at Yale-New Haven
    • Florida
      • Jacksonville, Florida, États-Unis, 32224
        • Recrutement
        • Mayo Clinic
    • Illinois
      • Chicago, Illinois, États-Unis, 60611
        • Recrutement
        • Northwestern Memorial Hospital
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02215
        • Recrutement
        • Dana Farber Cancer Institute
    • Minnesota
      • Rochester, Minnesota, États-Unis, 55905
        • Recrutement
        • Mayo Clinic
    • Nebraska
      • Omaha, Nebraska, États-Unis, 68198
        • Recrutement
        • Fred and Pamela Buffett Cancer Center
    • New Jersey
      • Hackensack, New Jersey, États-Unis, 07601
        • Complété
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, États-Unis, 14263
        • Recrutement
        • Roswell Park Comprehensive Cancer Center
      • New York, New York, États-Unis, 10065
        • Recrutement
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, États-Unis, 10032
        • Retiré
        • Columbia University Irving Medical Center
      • New York, New York, États-Unis, 10029
        • Recrutement
        • Mt Sinai
    • North Carolina
      • Durham, North Carolina, États-Unis, 27710
        • Recrutement
        • Duke University Medical Center, Duke Cancer Center
    • Ohio
      • Cleveland, Ohio, États-Unis, 44195
        • Recrutement
        • Cleveland Clinic
    • Oregon
      • Portland, Oregon, États-Unis, 97225
        • Recrutement
        • Providence Neurological Specialties West
    • Pennsylvania
      • Philadelphia, Pennsylvania, États-Unis, 19104
        • Complété
        • Hospital of the University of Pennsylvania
      • Pittsburgh, Pennsylvania, États-Unis, 15232
        • Recrutement
        • UPMC Hilman Cancer Center
    • Tennessee
      • Knoxville, Tennessee, États-Unis, 37920
        • Complété
        • University of Tennessee Medical Center
    • Texas
      • Dallas, Texas, États-Unis, 75235
        • Actif, ne recrute pas
        • UT Southwestern Medical Center
      • Houston, Texas, États-Unis, 77030
        • Recrutement
        • The University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, États-Unis, 84112
        • Recrutement
        • Huntsman Cancer Institute, University of Utah
    • Washington
      • Seattle, Washington, États-Unis, 98195
        • Recrutement
        • University of Washington Medical Center
      • Seattle, Washington, États-Unis, 98104
        • Complété
        • Swedish Cancer Institute

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  1. Males and females greater than or equal to 18 years of age

  2. Life expectancy of at least 3 months

  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

  4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable). Cerebral biopsies are not required if imaging reveals typical images of PCNSL.

    1. Participants with parenchymal lesions must have unequivocal evidence of disease progression (e.g., presence of at least 1 measurable target lesion [≥ 10 millimeters (mm) and ≤ 40 mm in the longest diameter on brain magnetic resonance imaging [MRI] or head computed tomography [CT] on imaging within 28 days prior to Cycle 1 Day 1]). In cases where the tumor size is smaller but still measurable and located at a critical central nervous system (CNS) location, disabling the participant and/or causing symptoms, this participant may be eligible following a discussion with the Sponsor Medical Monitor.
    2. For participants limited to leptomeningeal involvement, cerebrospinal fluid (CSF) analysis (cytology and/or flow cytometry) with or without additional imaging (MRI) of the spine as clinically indicated is required to document abnormal cells within 28 days prior to Cycle 1 Day 1.

Exclusion Criteria for Part B and Part C

  1. Participants with only intraocular PCNSL without brain lesion or CSF involvement, T-cell lymphoma, systemic presence of lymphoma, or non-CNS lymphoma metastatic to the CNS

  2. Evidence of systemic lymphoma. This must be demonstrated by a positron emission tomography (PET) scan (or CT scan with contrast if applicable) of the chest, abdomen, and pelvis at Screening (testicular ultrasound may be considered to exclude a testicular lymphoma disseminated to the brain).

  3. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior history of systemic lymphoma, unless the participant has been free of the disease for ≥ 3 years.

  4. Active malignancy other than PCNSL requiring systemic therapy

  5. Previous BTKi treatment (Part C only).

  6. History of Grade ≥ 3 rhabdomyolysis without complete recovery

  7. Requirement for urgent therapy due to uncontrolled tumor mass/edema effects.

  8. Received external beam radiation therapy to the CNS within 28 days prior to Cycle 1 Day 1.

  9. Received prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to Cycle 1 Day 1; or had clinically significant graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive medications prior to Screening (with the exception of a BTKi for Part B only).

    Note: The use of a stable or tapering dose of immunosuppressive therapy post-HSCT and/or topical steroids for ongoing skin GVHD is permitted with Sponsor Medical Monitor approval

  10. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1 (with the exception of ibrutinib or other BTKi for Part B only, which may be continued until the day before Cycle 1 Day 1)

  11. Prior history of hypersensitivity or anaphylaxis to emavusertib, ibrutinib or any of their excipients.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation séquentielle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Emavusertib (CA-4948) dose escalation

Part A1: Dose-level cohorts with up to approximately 6 participants each will be used to define the Maximum Tolerated Dose (MTD) for emavusertib.
Médicament: Emavusertib

Emavusertib will be provided as a tablet dosage form to be taken BID.

Autres noms:
  • CA-4948
Expérimental: Emavusertib (CA-4948) and ibrutinib dose escalation

Part A2: Evaluate escalating dose levels of oral emavusertib in combination with 560 mg QD or 420 mg QD of oral ibrutinib. The starting dose of emavusertib to be used in combination will be 200 mg BID. It is anticipated that 12 to 20 participants at a potential dose level will be required to establish optimal combination dosing.
Médicament: Emavusertib

Emavusertib will be provided as a tablet dosage form to be taken BID.

Autres noms:
  • CA-4948
Médicament: Ibrutinib

Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Expérimental: Emavusertib (CA-4948) and ibrutinib dose expansion

In two Expansion Cohorts (Part B), emavusertib in combination with ibrutinib will be administered in participants with R/R PCNSL who have progressed on a BTKi. In Cohort 1, emavusertib 100 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles. In Cohort 2, emavusertib 200 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles.
Médicament: Emavusertib

Emavusertib will be provided as a tablet dosage form to be taken BID.

Autres noms:
  • CA-4948
Médicament: Ibrutinib

Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Expérimental: Emavusertib (CA-4948) and ibrutinib

In this part of the study (Part C), eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will receive 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD. Treatments will be administered continuously in 28-day treatment cycles.
Médicament: Emavusertib

Emavusertib will be provided as a tablet dosage form to be taken BID.

Autres noms:
  • CA-4948
Médicament: Ibrutinib

Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Partie B : Taux de réponse global (ORR) chez les participants atteints de PCNSL R/R
Délai: 18 mois
18 mois
Partie C: ORR dans les participants avec R / R PCNSL
Délai: 18 mois
18 mois
Part A: To determine the safety and tolerability of emavusertib as a monotherapy and in combination with ibrutinib: dose-limiting toxicity (DLT)
Délai: 12 months

The number of participants with a dose-limiting toxicity (DLT) in the first treatment cycle
12 months
Part A: Maximum tolerated dose (MTD) of emavusertib as a monotherapy and in combination with ibrutinib measured by dose-limiting toxicities (DLTs)
Délai: 12 months

MTD determined by the highest dose level studied at which fewer than 2 out of 6 subjects (<33%) experience a dose limiting toxicity.
12 months
Part A: Recommended Phase 2 Dose (RP2D) of emavusertib as a monotherapy and in combination with ibrutinib based on overall tolerability data
Délai: 12 months

RP2D selected based on overall tolerability data from all participants treated at different dose levels and will not exceed the MTD.
12 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by AUC
Délai: 24- 66 months

Area Under the concentration-time curve (AUC)
24- 66 months
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by Cmax
Délai: 24- 66 months

Maximum plasma concentration (Cmax)
24- 66 months
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by Cmin
Délai: 24- 66 months

Minimum plasma concentration (Cmin)
24- 66 months
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by Tmax
Délai: 24- 66 months

Time to maximum plasma concentration (Tmax)
24- 66 months
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by plasma terminal half-life
Délai: 24- 66 months

Plasma terminal elimination half-life (T 1/2)
24- 66 months
Part A: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib measured by ORR
Délai: 24- 36 months

Assessed by ORR
24- 36 months
Parts A, B and C: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib and ibrutinib as monotherapy measured by duration of response (DOR)
Délai: 24- 66 months

Assessed by DOR
24- 66 months
Part A: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib measured by disease control rate (DCR)
Délai: 24- 36 months

Assessed by DCR
24- 36 months
Parts A, B and C: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib and ibrutinib as monotherapy measured by progression free survival (PFS)
Délai: 24- 66 months

Assessed by PFS
24- 66 months
Parts A, B and C: To assess efficacy of emavusertib as a monotherapy, in combination with ibrutinib and ibrutinib as monotherapy measured by overall survival (OS)
Délai: 24 - 66 months

Assessed by OS
24 - 66 months
Parts B and C: To assess the safety and tolerability of emavusertib as monotherapy, ibrutinib as monotherapy and emavusertib in combination with ibrutinib in participants with R/R PCNSL
Délai: up to 66 months

Measured by the number of participants with treatment-emergent adverse events (TEAEs) and treatment-related adverse events
up to 66 months

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Curis, Inc.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

28 décembre 2017

Achèvement primaire (Estimé)

1 juillet 2027

Achèvement de l'étude (Estimé)

1 octobre 2027

Dates d'inscription aux études

Première soumission

17 octobre 2017

Première soumission répondant aux critères de contrôle qualité

27 octobre 2017

Première publication (Réel)

1 novembre 2017

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

6 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

1 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CA-4948-101
  • 2024-513312-95-00 (Ctis)
  • 2022-000891-20 (Numéro EudraCT)

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

S'abonner