ALL, CLL/SLL and DLBCL, and High-Risk LBCL. MedDRA version: 21.0 Level: PT Classification code 10003917 Term: B-cell type acute leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10003899 Term: B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Rapcabtagene autoleucel
Product Code: YTB323
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Rapcabtagene autoleucel
Current Sponsor code: YTB323
Concentration unit: Ot
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •= 18 years old •For ALL and DLBCL: ECOG 0-1 •For HR LBCL: ECOG 0-2 •DLBCL: -Diagnosis by local histopathology -Relapsed or refractory disease having received 2 or more lines of systemic therapy, including anti-CD20 and anthracycline-based chemotherapy, and either having progressed (or relapsed) after autologous HSCT, or being ineligible for or not consenting to the procedure. •ALL relapsed or refractory including at least 1 of the following: after allogeneic HSCT, after 2 or more lines of treatment, primary refractory disease, first relapse occurring within 12 months from first remission; patients with Philadelphia chromosome-positive ALL must have failed at least 2 different tyrosine kinase inhibitors or are intolerant. •HR LBCL cohort: -Histologically confirmed large B-cell non-Hodgkin lymphoma. -Considered to be high-risk (IPI 3-5, MYC and BCL2 and/or BCL6). -Participants must have received 2 cycles of frontline therapy for LBCL (R-CHOP, Pola-R-CHP, DA-EPOCH-R). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 112 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 112
Exclusion criteria
Exclusion criteria: • Prior CD19-directed therapy with the exception of blinatumomab for patients with ALL • Prior administration of a genetically engineered cellular product • Prior allogeneic HSCT (DLBCL only) • Richter's transformation • For DLBCL: Primary Central Nervous System (CNS) lymphoma or DLBCL with active CNS involvement, except if CNS involvement has been effectively treated and provided that treatment was > 4 weeks before screening. • For HR LBCL: Active CNSinvolvement by malignancy. • For ALL: presence of CNS-2 disease with neurological changes or CNS-3 disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Dose recommendation - Safety - Tolerability - Manufacture success Phase II - DLBCL and HR LBCL cohorts only: - Antitumor activity of rapcabtagene autoleucel single agent ;Secondary Objective: - Cellular kinetics - Immunogenicity - Tumor response in CLL/SLL - Tumor response in DLBCL - Tumor response in ALL - Tumor response in HR LBCL - Safety;Primary end point(s): - Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only) - Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs - Ibrutinib dose modifications in the CLL/SLL arm - Number of patients infused with planned target dose Phase II part - DLBCL: - CRR defined as BOR of CR after rapcabtagene infusion Phase II part - HR LBCL: - CRR defined as BOR of CR after rapcabtagene infusion ;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Phase I part - CLL/SLL, DLBCL, ALL: -CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood, bone marrow and lymph nodes -Cellular and humoral responses to the CAR transgene -BOR as CR/PR per iwCLL response criteria, DOR - Disease response (CR/PR) per Lugano criteria, DOR, OS - BOR as CR/CRi, disease response (CR/CRi), DOR, EFS, OS, MRD status • Phase II part - DLBCL: -Overall response rate (ORR) defined as BOR of CR/PR as per Lugano criteria -CRR at months 3 and 6 -Duration of response (DOR), defined as time from first CR/PR to first documented progression or death due to any cause -Progression-free survival (PFS) defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause -Overall survival (OS), defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause • Phase II part - HR LBCL: -Overall response rate (ORR) defined as BOR of CR/PR as per Lugano criteria -CRR at months 6 and 12 -Duration of response (DOR). defined as time from first CR/PR to first documented progression or death due to any cause -Progression-free survival (PFS) defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause -Event-free survival (EFS\ defined as time from rapcabtagene autoleucel infusion to first documented progression, start of new anti-lymphoma therapy, biopsy-proven residual disease on or after month 6, or death due to any cause -Overall survival (OS), defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
Australia, Austria, France, Germany, Italy, Japan, Spain, United States
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed