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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
| 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 :
- 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 ]
Secondary Outcome Measures :
- 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 ]
Eligibility Criteria
| 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
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | novartis.email@novartis.com | |
| Contact: Novartis Pharmaceuticals | +41613241111 |
Locations
| 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 |
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| 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 |
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| Condition ICMJE | Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Large B-cell Lymphoma; Acute Lymphoblastic Leukemia | ||||||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE |
110 | ||||||||
| Original Estimated Enrollment ICMJE |
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:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
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| 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 |
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| IPD Sharing Statement ICMJE |
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| 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 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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