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Uno studio sul CA-4948 in pazienti con neoplasie ematologiche recidivanti o refrattarie

1 ottobre 2026 aggiornato da: Curis, Inc.

TakeAim Lymphoma: uno studio in aperto, aumento della dose e espansione della dose che valuta la sicurezza, la farmacocinetica, la farmacodinamica e l'attività clinica del CA-4948 somministrato per via orale in pazienti con neoplasie ematologiche recidivanti o refrattarie

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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Stimato)

152

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione sequenziale
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: Emavusertib

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

Altri nomi:
  • CA-4948
Sperimentale: 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.
Droga: Emavusertib

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

Altri nomi:
  • CA-4948
Droga: Ibrutinib

Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Sperimentale: 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.
Droga: Emavusertib

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

Altri nomi:
  • CA-4948
Droga: Ibrutinib

Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Sperimentale: 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.
Droga: Emavusertib

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

Altri nomi:
  • CA-4948
Droga: Ibrutinib

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

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Parte B: tasso di risposta globale (ORR) nei partecipanti con PCNSL R/R
Lasso di tempo: 18 mesi
18 mesi
Parte C: ORR nei partecipanti con R/R PCNSL
Lasso di tempo: 18 mesi
18 mesi
Part A: To determine the safety and tolerability of emavusertib as a monotherapy and in combination with ibrutinib: dose-limiting toxicity (DLT)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by AUC
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Curis, Inc.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

28 dicembre 2017

Completamento primario (Stimato)

1 luglio 2027

Completamento dello studio (Stimato)

1 ottobre 2027

Date di iscrizione allo studio

Primo inviato

17 ottobre 2017

Primo inviato che soddisfa i criteri di controllo qualità

27 ottobre 2017

Primo Inserito (Effettivo)

1 novembre 2017

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

6 ottobre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

1 ottobre 2026

Ultimo verificato

1 ottobre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

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

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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