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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03960840
Recruitment Status : Recruiting
First Posted : May 23, 2019
Last Update Posted : September 9, 2020
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 : March 27, 2024
Estimated Study Completion Date : March 27, 2024


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 ]


Information from the National Library of Medicine

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

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, 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, Tennessee
Sarah Cannon Research Institute Drug Ship - 4 Recruiting
Nashville, Tennessee, United States, 37203
Contact    615-329-7274      
Principal Investigator: Ian W. Flinn         
United States, Wisconsin
Medical College of Wisconsin, Inc. Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Laura Wall    414-805-4600    lwall@mcw.edu   
Principal Investigator: Nirav Shah         
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
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: September 9, 2020
Last Verified: September 2020
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