ALL, CLL/SLL and DLBCL and High-Risk LBCL.
Conditions
Interventions
Product Name: Rapcabtagene autoleucel
Product Code: YTB323
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Rapcabtagene autoleucel
Current Sponsor code: YTB323
Concentration unit: O
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. •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) •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 (DH/TH)). - Participants must have received 2 cycles of frontline therapy for LBCL (R-CHOP, Pola-R-CHP, DA-EPOCH-R). Participants with DH/TH lymphoma must have received at least one cycle (the most recent cycle) of DAEPOCH-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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
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 (CLL and DLBCL only) • Richter's transformation • Uncontrolled seizure disorder • History of deep venous thrombosis or pulmonary embolus • 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 CNS involvement by malignancy -Patients who are candidates for abbreviated (<6 cycles) CIT with or without consecutive radiotherapy • For ALL: -presence of CNS-2 disease with neurological changes or CNS-3 disease -ALL that has evolved from an antecedent myeloid neoplasm or that harbors evidence of de novo presentation of a lymphoid blast phase of a previously undiagnosed myeloid neoplasm.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I - 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): • 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 ContactDrug Regulatory Affairs
Novartis Pharma GmbH
Outcome results
None listed