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Imfinzi NSCLC
Imfinzi NSCLC

JOURNAL ONKOLOGIE – STUDIE

CD19-specific CAR-T Cells in CLL/SLL and DLBCL

Rekrutierend

NCT-Nummer:
NCT03960840

Studienbeginn:
Juni 2019

Letztes Update:
19.01.2021

Wirkstoff:
YTB323 and ibrutinib, YTB323 single agent

Indikation (Clinical Trials):
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Kontakt

Studienlocations (3 von 10)

University of Chicago Medical Center Hematology and Oncology
60637 Chicago
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Elaine Hoekstra
Phone: 773-834-8980
E-Mail: ehoekstra1@medicine.bsd.uchicago.edu
» Ansprechpartner anzeigen
Novartis Investigative Site
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
13273 Marseille
FranceRekrutierend» Google-Maps
Novartis Investigative Site
69495 Pierre Benite Cedex
FranceRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This is a first-in-human study to evaluate the feasibility, safety and preliminary antitumor

efficacy of autologous T cells genetically engineered with a CD19-specific chimeric antigen

receptor (CAR) and manufactured with a new process. CAR-T cells will be investigated in

combination with ibrutinib in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma

(SLL) and as single agent in diffuse large B-cell lymphoma (DLBCL) and in adult acute

lymphoblastic leukemia (ALL).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- ECOG performance status 0-1

- CLL or SLL diagnosis according to iwCLL criteria

- CLL/SLL in SD or PR after at least 6 months of ibrutinib, either as second or

subsequent line of therapy

- DLBCL diagnosis by local histopathology

- DLBCL relapsed or refractory after 2 or more lines of therapy, including autologous

hematopoietic stem cell transplantation (HSCT)

- Refractory or relapsed CD19-positive ALL

- ALL with morphologic disease in the bone marrow

Exclusion Criteria:

- Prior CD19-directed therapy

- Prior administration of a genetically engineered cellular product

- Prior allogeneic HSCT

- Richter's transformation

- Active CNS lymphoma

- Targeted small molecule or kinase inhibitor within 2 weeks from leukapheresis

- Anti-CD20 monoclonal antibodies within 4 weeks prior to infusion

Studien-Rationale

Primary outcome:

1. Dose recommendation: incidence and nature of Dose Limiting Toxicities (Dose Escalation part only) (Time Frame - 24 months)

2. Safety: incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs (Time Frame - 24 months)

3. Tolerability: ibrutinib dose modifications in the CLL/SLL arm (Time Frame - 24 months)

4. Manufacture success: number of patients infused with planned target dose (Time Frame - 24 months)

Secondary outcome:

1. Cellular kinetics: CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood, bone marrow and lymph nodes (Time Frame - 24 months)

2. Immunogenicity: cellular and humoral responses to the CAR transgene (Time Frame - 24 months)

3. Tumor response in CLL/SLL: CR/PR per iwCLL response criteria (Time Frame - 24 months)

4. Tumor response in DLBCL: ORR/CR/PR per Lugano criteria (Time Frame - 24 months)

5. Duration of response (DOR) in CLL/SLL and DLBCL (Time Frame - 24 months)

6. Tumor response in ALL: ORR as assessed by an Independent Review Committee (Time Frame - 24 months)

7. Tumor response in ALL: DOR as assessed by an Independent Review Committee (Time Frame - 24 months)

8. Tumor response in ALL: EFS as assessed by an Independent Review Committee (Time Frame - 24 months)

9. Tumor response in ALL: ORR as assessed by local Investigator (Time Frame - 24 months)

10. Tumor response in ALL: DOR as assessed by local Investigator (Time Frame - 24 months)

11. Tumor response in ALL: EFS as assessed by local Investigator (Time Frame - 24 months)

12. Overall survival in adult ALL (Time Frame - 24 months)

13. MRD negative status by flow cytometry in adult ALL (Time Frame - 24 months)

Studien-Arme

  • Experimental: CLL/SLL
    Dose escalation and expansion of YTB323 in combination with ibrutinib
  • Experimental: DLBCL
    Dose escalation and expansion of YTB323 single agent in DLBCL
  • Experimental: Adult ALL
    Dose escalation and expansion of YTB323 single agent in adult ALL

Geprüfte Regime

  • YTB323 and ibrutinib:
    Single infusion of YTB323 and daily ibrutinib
  • YTB323 single agent:
    Single infusion of YTB323

Quelle: ClinicalTrials.gov


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