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Een studie van CA-4948 bij patiënten met recidiverende of refractaire hematologische maligniteiten

1 oktober 2026 bijgewerkt door: Curis, Inc.

TakeAim-lymfoom: een open-label onderzoek naar dosisescalatie en dosisuitbreiding ter evaluatie van de veiligheid, farmacokinetiek, farmacodynamiek en klinische activiteit van oraal toegediend CA-4948 bij patiënten met recidiverende of refractaire hematologische maligniteiten

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Geschat)

152

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Sequentiële toewijzing
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Geneesmiddel: Emavusertib

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

Andere namen:
  • CA-4948
Experimenteel: 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.
Geneesmiddel: Emavusertib

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

Andere namen:
  • CA-4948
Geneesmiddel: Ibrutinib

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

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

Andere namen:
  • CA-4948
Geneesmiddel: Ibrutinib

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

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

Andere namen:
  • CA-4948
Geneesmiddel: Ibrutinib

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

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Deel B: Algemeen responspercentage (ORR) bij deelnemers met R/R PCNSL
Tijdsspanne: 18 maanden
18 maanden
Deel C: ORR bij deelnemers met R/R PCNSL
Tijdsspanne: 18 maanden
18 maanden
Part A: To determine the safety and tolerability of emavusertib as a monotherapy and in combination with ibrutinib: dose-limiting toxicity (DLT)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by AUC
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Curis, Inc.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

28 december 2017

Primaire voltooiing (Geschat)

1 juli 2027

Studie voltooiing (Geschat)

1 oktober 2027

Studieregistratiedata

Eerst ingediend

17 oktober 2017

Eerst ingediend dat voldeed aan de QC-criteria

27 oktober 2017

Eerst geplaatst (Werkelijk)

1 november 2017

Updates van studierecords

Laatste update geplaatst (Werkelijk)

6 oktober 2026

Laatste update ingediend die voldeed aan QC-criteria

1 oktober 2026

Laatst geverifieerd

1 oktober 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

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

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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