En undersøgelse til evaluering af sikkerhed, PK, PD og effektivitet af AZD5492, et T-celle-engagerende antistof rettet mod CD20 hos forsøgspersoner med R/R B-celle maligniteter. (TITANium)
En modulær fase I/II åben-label dosiseskalering og dosisudvidelsesundersøgelse for at evaluere sikkerheden, farmakokinetik, farmakodynamik og effektivitet af AZD5492, et T-celle-engagerende antistof rettet mod CD20 hos forsøgspersoner med recidiverende eller refraktære B-celle maligniteter
This is a Phase I/II study designed to evaluate if experimental T cell engaging antibody targeting CD20 AZD5492 is safe, tolerable and efficacious in participants with Relapsed or Refractory B-Cell Malignancies.
Studieoversigt
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiekontakt
- Navn: AstraZeneca Clinical Study Information Center
- Telefonnummer: 1-877-240-9479
- E-mail: information.center@astrazeneca.com
Studiesteder
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Melbourne, Australien, 3000
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- Research Site
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Nedlands, Australien, 6009
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Alberta
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Calgary, Alberta, Canada, T2N 5G2
- Rekruttering
- Research Site
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- Rekruttering
- Research Site
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Quebec
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Montreal, Quebec, Canada, H3T 1R2
- Rekruttering
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København Ø, Danmark, 2100
- Rekruttering
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California
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La Jolla, California, Forenede Stater, 92093
- Rekruttering
- Research Site
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02215
- Trukket tilbage
- Research Site
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Rekruttering
- Research Site
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New Jersey
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Hackensack, New Jersey, Forenede Stater, 07601
- Rekruttering
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New York
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New York, New York, Forenede Stater, 10021
- Rekruttering
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New York, New York, Forenede Stater, 10029
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North Carolina
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Charlotte, North Carolina, Forenede Stater, 28203
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Winston-Salem, North Carolina, Forenede Stater, 27157
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Texas
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Houston, Texas, Forenede Stater, 77030
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Washington
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Seattle, Washington, Forenede Stater, 98109
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Pessac, Frankrig, 33604
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Villejuif, Frankrig, 94805
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Bologna, Italien, 40138
- Rekruttering
- Research Site
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Milan, Italien, 20133
- Rekruttering
- Research Site
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Chūōku, Japan, 104-0045
- Rekruttering
- Research Site
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Kashiwa, Japan, 277-8577
- Rekruttering
- Research Site
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Hangzhou, Kina, 310003
- Rekruttering
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Shanghai, Kina, 200025
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Barcelona, Spanien, 08035
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L'Hospitalet de Llobregat, Spanien, 08908
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Madrid, Spanien, 28040
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Göttingen, Tyskland, DE-37099
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München, Tyskland, 81675
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Ulm, Tyskland, 89081
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Würzburg, Tyskland, 97080
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
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≥18 years of age;
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Histologically documented CD20+ mature B-cell neoplasm
- Large B-cell lymphoma
- Follicular lymphoma
- Mantle cell lymphoma
- Chronic lymphocytic leukemia
- Small lymphocytic lymphoma
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Relapsed, progressive and/or refractory disease following at least 2 prior lines of therapy;
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ECOG performance status of ≤ 2 (< 2 in EU countries).
The above is a summary, other inclusion criteria details may apply.
Exclusion Criteria:
- Any neoplasm histology not specified in the IC section;
- Active CNS involvement in lymphoma;
- CNS pathology including but not limited to any history of seizure disorder/epilepsy;
- Prior allogeneic HSCT within 180 days, prior autologous HSCT within 90 days, or cell therapy within 90 days of start of therapy;
- History of Grade ≥ 3 CRS or Grade ≥ 3 ICANS;
- Active and uncontrolled infections;
- Unresolved AEs ≥2 Grade due to prior anticancer therapies, with some exceptions
The above is a summary, other exclusion criteria details may apply.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Module 1: AZD5492 Monotherapy
AZD5492 monotherapy for Relapsed or Refractory B-Cell Malignancies. |
CD8/TCR based T-cell engaging antibody targeting CD20, which is administered subcutaneously |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Frequency of dose limiting toxicities (DLTs).
Tidsramme: Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).
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DLTs are dose-limiting toxicities as defined in the study protocol. |
Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).
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Safety evaluation of AZD5492: Number of participants with treatment-related adverse events.
Tidsramme: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
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Incidence and severity of AEs, AESIs, and SAEs |
Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
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Tolerability evaluation of AZD5492: Number of participants with treatment-related adverse events.
Tidsramme: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
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SAEs/AEs leading to discontinuation of AZD5492. |
Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Overall Response Rate (ORR)
Tidsramme: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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The proportion of participants with a complete response or partial response, according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL. |
Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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Complete Response Rate (CR Rate)
Tidsramme: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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The proportion of participants with a complete response (CR), according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL. |
Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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Duration of Response (DoR)
Tidsramme: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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The time from the date of first documented response until the date of documented progression (according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL) or death due to any cause. |
Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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Progression-free Survival (PFS)
Tidsramme: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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The time from the date of first dose until the date of documented disease progression (according to Lugano criteria for malignant lymphoma and iwCLL 2018 criteria for CLL) or death due to any cause. |
Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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Overall Survival (OS)
Tidsramme: Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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The time from the date of first dose until date of death due to any cause. |
Module 1 - From first dose of AZD5492 up to 2 years after last dose.
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Pharmacokinetics of AZD5492: serum concentration of study drug
Tidsramme: Module 1 - From informed consent until 90 days after last dose of AZD5492.
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Maximum observed serum concentration of AZD5492. |
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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Pharmacokinetics of AZD5492: Maximum plasma concentration of the study drug (Cmax).
Tidsramme: Module 1 - From informed consent until 90 days after last dose of AZD5492.
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Maximum observed plasma concentration of AZD5492. |
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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Pharmacokinetics of AZD5492: Area under the concentration time curve (AUC).
Tidsramme: Module 1 - From informed consent until 90 days after last dose of AZD5492.
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Area under the plasma concentration-time curve. |
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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Pharmacokinetics of AZD5492: apparent clearance
Tidsramme: Module 1 - From informed consent until 90 days after last dose of AZD5492.
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The volume of plasma from which the study drug is completely removed per unit time. |
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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Pharmacokinetics of AZD5492: Half-life (t 1/2)
Tidsramme: Module 1 - From informed consent until 90 days after last dose of AZD5492.
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Terminal elimination half-life. |
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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To determine the immunogenicity of AZD5492
Tidsramme: Module 1 - From informed consent until 90 days after last dose of AZD5492.
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The number of participants who develop ADAs measured in serum. |
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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To determine the immunogenicity of AZD5492
Tidsramme: Module 1 - From informed consent until 90 days after last dose of AZD5492.
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The percentage of participants who develop ADAs measured in serum. |
Module 1 - From informed consent until 90 days after last dose of AZD5492.
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Samarbejdspartnere og efterforskere
Sponsor
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Neoplasmer
- Kronisk sygdom
- Sygdomsegenskaber
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Hæmatologiske sygdomme
- Lymfesygdomme
- Lymfoproliferative lidelser
- Immunproliferative lidelser
- Lymfom, Non-Hodgkin
- Lymfom
- Leukæmi, lymfoid
- Leukæmi
- Patologiske tilstande, tegn og symptomer
- Hemiske og lymfatiske sygdomme
- Tilbagevenden
- Leukæmi, lymfatisk, kronisk, B-celle
- Lymfom, follikulært
- Lymfom, kappecelle
- Leukæmi, B-celle
Andre undersøgelses-id-numre
- D9960C00001
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal
Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:
https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
IPD-delingstidsramme
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/.
IPD-delingsadgangskriterier
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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