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出境医 / 临床实验 / CD19-specific CAR-T Cells in CLL/SLL and DLBCL

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

Study Description
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

Study Design
Layout table for study information
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 8, 2025
Estimated Study Completion Date : October 8, 2025
Arms and Interventions
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
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

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

Locations
Layout table for location information
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: William Wesson    913-588-6029    wwesson@kumc.edu   
Principal Investigator: Leyla Shune         
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact    617-726-2000      
Principal Investigator: Matthew Frigault         
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
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Barcelona, Spain, 08041
Sponsors and Collaborators
Novartis Pharmaceuticals
Tracking Information
First Submitted Date  ICMJE May 21, 2019
First Posted Date  ICMJE May 23, 2019
Last Update Posted Date May 14, 2021
Actual Study Start Date  ICMJE June 27, 2019
Estimated Primary Completion Date October 8, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • Dose recommendation: incidence and nature of Dose Limiting Toxicities (Dose Escalation part only) [ Time Frame: 24 months ]
  • Safety: incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs [ Time Frame: 24 months ]
  • Tolerability: ibrutinib dose modifications in the CLL/SLL arm [ Time Frame: 24 months ]
  • Manufacture success: number of patients infused with planned target dose [ Time Frame: 24 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2021)
  • Cellular kinetics: CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood, bone marrow and lymph nodes [ Time Frame: 24 months ]
  • Immunogenicity: cellular and humoral responses to the CAR transgene [ Time Frame: 24 months ]
  • Tumor response in CLL/SLL: CR/PR per iwCLL response criteria [ Time Frame: 24 months ]
  • Tumor response in DLBCL: ORR/CR/PR per Lugano criteria [ Time Frame: 24 months ]
  • Duration of response (DOR) in CLL/SLL and DLBCL [ Time Frame: 24 months ]
  • Tumor response in ALL: ORR as assessed by an Independent Review Committee [ Time Frame: 24 months ]
  • Tumor response in ALL: DOR as assessed by an Independent Review Committee [ Time Frame: 24 months ]
  • Tumor response in ALL: EFS as assessed by an Independent Review Committee [ Time Frame: 24 months ]
  • Tumor response in ALL: ORR as assessed by local Investigator [ Time Frame: 24 months ]
  • Tumor response in ALL: DOR as assessed by local Investigator [ Time Frame: 24 months ]
  • Tumor response in ALL: EFS as assessed by local Investigator [ Time Frame: 24 months ]
  • Overall survival in adult ALL [ Time Frame: 24 months ]
  • MRD negative status by flow cytometry in adult ALL [ Time Frame: 24 months ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • Cellular kinetics: CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood, bone marrow and lymph nodes [ Time Frame: 24 months ]
  • Immunogenicity: cellular and humoral responses to the CAR transgene [ Time Frame: 24 months ]
  • Tumor response in CLL/SLL: CR/PR per iwCLL response criteria [ Time Frame: 24 months ]
  • Tumor response in DLBCL: ORR/CR/PR per Lugano criteria [ Time Frame: 24 months ]
  • Duration of response (DOR) in CLL/SLL and DLBCL [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CD19-specific CAR-T Cells in CLL/SLL and DLBCL
Official Title  ICMJE Phase I, Open Label, Multicenter, Dose Escalation Study of CD19-specific CAR-T Cells in Adult Patients With CLL/SLL and DLBCL
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Large B-cell Lymphoma; Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Drug: YTB323 and ibrutinib
    Single infusion of YTB323 and daily ibrutinib
  • Drug: YTB323 single agent
    Single infusion of YTB323
Study Arms  ICMJE
  • Experimental: CLL/SLL
    Dose escalation and expansion of YTB323 in combination with ibrutinib
    Intervention: Drug: YTB323 and ibrutinib
  • Experimental: DLBCL
    Dose escalation and expansion of YTB323 single agent in DLBCL
    Intervention: Drug: YTB323 single agent
  • Experimental: Adult ALL
    Dose escalation and expansion of YTB323 single agent in adult ALL
    Intervention: Drug: YTB323 single agent
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 27, 2020) 		110
Original Estimated Enrollment  ICMJE
 (submitted: May 21, 2019) 		50
Estimated Study Completion Date  ICMJE October 8, 2025
Estimated Primary Completion Date October 8, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Australia,   Austria,   France,   Italy,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03960840
Other Study ID Numbers  ICMJE CYTB323A12101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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