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

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ClinicalTrials.gov Identifier: NCT03960840
Recruitment Status : Recruiting
First Posted : May 23, 2019
Last Update Posted : November 19, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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).

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Open Label, Multicenter, Dose Escalation Study of CD19-specific CAR-T Cells in Adult Patients With CLL/SLL and DLBCL
Actual Study Start Date : June 27, 2019
Estimated Primary Completion Date : October 9, 2025
Estimated Study Completion Date : October 9, 2025


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




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 ]


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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

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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United States, Florida
H Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: John Dewolfe    888-663-3488    John.Dewolfe@moffitt.org   
Principal Investigator: Javier Pinilla-Ibarz         
United States, Illinois
University of Chicago Medical Center Hematology and Oncology Recruiting
Chicago, Illinois, United States, 60637
Contact: Elaine Hoekstra    773-834-8980    ehoekstra1@medicine.bsd.uchicago.edu   
Principal Investigator: Peter Riedell         
United States, Kansas
University of Kansas Cancer Center SC - CTL019C2201 Recruiting
Westwood, Kansas, United States, 66205
Contact: Morgan Albright    913-588-6029    malbright3@kumc.edu   
Principal Investigator: Leyla Shune         
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Devin Walsh    617-726-2000    dwalsh18@mgh.harvard.edu   
Principal Investigator: Matthew Frigault         
United States, Pennsylvania
University of Pennsylvania Clinical Studies Unit Perelman Center for Adv Med Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Rachael Purri    215-615-6721    rachael.purri@pennmedicine.upenn.edu   
Principal Investigator: Noelle Frey         
United States, Tennessee
Sarah Cannon Research Institute Drug Ship - 4 Recruiting
Nashville, Tennessee, United States, 37203
Contact: David J Pruitt    615-329-7274    David.Pruitt@SarahCannon.com   
Principal Investigator: Ian W. Flinn         
United States, Wisconsin
Medical College of Wisconsin, Inc. Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Nicole Raykovich    414-805-4600    nraykovich@mcw.edu   
Principal Investigator: Nirav Shah         
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
Austria
Novartis Investigative Site Recruiting
Wien, Austria, A-1090
France
Novartis Investigative Site Recruiting
Marseille, France, 13273
Novartis Investigative Site Recruiting
Paris Cedex 10, France, 75475
Novartis Investigative Site Recruiting
Pierre Benite Cedex, France, 69495
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20132
Spain
Novartis Investigative Site Recruiting
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Barcelona, Spain, 08041
Novartis Investigative Site Recruiting
Madrid, Spain, 28009
Sponsors and Collaborators
Novartis Pharmaceuticals
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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: November 19, 2021
Last Verified: November 2021
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 ):
CD19 CAR-T cells, CLL, SLL, ibrutinib, DLBCL, ALL
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
Leukemia, B-Cell
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin