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

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ClinicalTrials.gov Identifier: NCT03960840
Recruitment Status : Recruiting
First Posted : May 23, 2019
Last Update Posted : March 8, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
This is a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of YTB323. YTB323 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).

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Large B-cell Lymphoma; Acute Lymphoblastic Leukemia Drug: YTB323 and ibrutinib Drug: YTB323 single agent Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Open Label, Multicenter, Dose Escalation Study of YTB323 in Adult Patients With CLL/SLL, DLBCL and ALL
Actual Study Start Date : June 27, 2019
Estimated Primary Completion Date : June 30, 2027
Estimated Study Completion Date : June 30, 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Ibrutinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: CLL/SLL
Dose escalation and expansion of YTB323 in combination with ibrutinib
 Drug: YTB323 and ibrutinib
Single infusion of YTB323 and daily ibrutinib
Experimental: DLBCL
Dose escalation and expansion of YTB323 single agent in DLBCL
 Drug: YTB323 single agent
Single infusion of YTB323
Experimental: Adult ALL
Dose escalation and expansion of YTB323 single agent in adult ALL
 Drug: YTB323 single agent
Single infusion of YTB323


Outcome Measures
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Primary Outcome Measures :
  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 Measures :
  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 ]
  14. Quality of life in adult ALL patients enrolled in the expansion part by use of Electronic Patient Reported Outcomes (ePRO) as per EORTC QLQ-C30 questionnaire [ Time Frame: 24 months ]
  15. Quality of life in adult ALL patients enrolled in the expansion part by use of Electronic Patient Reported Outcomes (ePRO) as per EQ-5D-3 questionnaire [ Time Frame: 24 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03960840


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03960840    
Other Study ID Numbers: CYTB323A12101
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: March 8, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
CAR-T, ibrutinib, CLL, DLBCL, ALL, BLRM, YTB323
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, Lymphoid
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Leukemia, B-Cell