Description:
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).
Title
- Brief Title: CD19-specific CAR-T Cells in CLL/SLL and DLBCL
- Official Title: Phase I, Open Label, Multicenter, Dose Escalation Study of CD19-specific CAR-T Cells in Adult Patients With CLL/SLL and DLBCL
Clinical Trial IDs
- ORG STUDY ID:
CYTB323A12101
- NCT ID:
NCT03960840
Conditions
- Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Large B-cell Lymphoma; Acute Lymphoblastic Leukemia
Interventions
| Drug | Synonyms | Arms |
|---|
| YTB323 and ibrutinib | | CLL/SLL |
| YTB323 single agent | | Adult ALL |
Purpose
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).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| CLL/SLL | Experimental | Dose escalation and expansion of YTB323 in combination with ibrutinib | |
| DLBCL | Experimental | Dose escalation and expansion of YTB323 single agent in DLBCL | |
| Adult ALL | Experimental | Dose escalation and expansion of YTB323 single agent in adult ALL | |
Eligibility 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose recommendation: incidence and nature of Dose Limiting Toxicities (Dose Escalation part only) |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Cellular kinetics: CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood, bone marrow and lymph nodes |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Immunogenicity: cellular and humoral responses to the CAR transgene |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Tumor response in CLL/SLL: CR/PR per iwCLL response criteria |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Tumor response in DLBCL: ORR/CR/PR per Lugano criteria |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of response (DOR) in CLL/SLL and DLBCL |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Tumor response in ALL: ORR as assessed by an Independent Review Committee |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Tumor response in ALL: DOR as assessed by an Independent Review Committee |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Tumor response in ALL: EFS as assessed by an Independent Review Committee |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Tumor response in ALL: ORR as assessed by local Investigator |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Tumor response in ALL: DOR as assessed by local Investigator |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Tumor response in ALL: EFS as assessed by local Investigator |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Overall survival in adult ALL |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | MRD negative status by flow cytometry in adult ALL |
| Time Frame: | 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- CD19 CAR-T cells, CLL, SLL, ibrutinib, DLBCL, ALL
Last Updated
June 30, 2021
