Rapcabtagene autoleucel single agent: Single infusion of rapcabtagene autoleucel
Ibrutinib: Tablets or capsules for oral daily use
Study summary
This is a phase I/II study to evaluate the feasibility, safety and preliminary antitumor efficacy of rapcabtagene autoleucel (also known as YTB323). Rapcabtagene autoleucel 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 (3L+ DLBCL), adult acute lymphoblastic leukemia (ALL) and 1st Line High Risk Large B-Cell Lymphoma (1L HR LBCL).
Eligibility
Sex
ALL
Min age
18 Years
Max age
100 Years
Healthy volunteers
No
Inclusion Criteria:
* ECOG performance status 0-1 for ALL and DLBCL
* ECOG performance status 0-2 for 1L HR LBCL at screening
* 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
1L HR LBCL - Considered to be high-risk based on at least 1 of the following at diagnosis:
* IPI score of 3, 4 or 5
* MYC and BCL2 and/or BCL6 rearrangement (DH/TH lymphoma)
* Participants must have received 2 cycles of frontline therapy for LBCL with R-CHOP or Pola-R-CHP or DA-EPOCH-R. Participants with DH/TH lymphoma must have received at least one cycle (the most recent) DA-EPOCH-R.
* Participants must have a positive PET per Lugano classification (Deauville PET score of 4 or 5 and an overall response of PR/SD) after 2 cycles of frontline CIT. Note: Patient's with Deauville PET score of 5 and overall response of PD, or with Deauville PET score of 1, 2, or 3 and overall response of CR, are not eligible for this trial.
Exclusion Criteria:
* Prior CD19-directed therapy
* Prior administration of a genetically engineered cellular product
* Prior allogeneic HSCT
* Richter's transformation
* For 1L HR LBCL: Richter's transformation, Burkitt lymphoma, primary DLBCL of CNS, DLBCL associated with chronic inflammation, intravascular large B-cell lymphoma, ALK- positive large B-cell lymphoma, HHV8 positive LBCL, DLBCL leg type or EBV positive DLBCL, NOS.
* Active CNS lymphoma
* For 1L HR LBCL: Active or prior history CNS involvement by malignancy
* Targeted small molecule or kinase inhibitor within 2 weeks from leukapheresis
Other protocol-defined inclusion/exclusion may apply.
Primary outcome measure(s)
Phase 1: Dose recommendation: Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only) — 28 days
Phase 1: Safety: Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs — 24 months
Phase 1: Tolerability: Ibrutinib dose modifications in the CLL/SLL arm — 24 months
Phase 1: Manufacture success: Number of patients infused with planned target dose — 24 months
Phase 2: Complete Response Rate (CRR) as assessed by local Investigator — 24 months CRR defined as best overall response (BOR) of CR after rapcabtagene autoleucel infusion as per Lugano criteria for 3L+ Diffuse Large B-Cell Lymphoma (DLBCL) and 1L High Risk Large B-Cell (HR LBCL)
Trial sites (37)
Facility
City
Region
Status
University of California LA
Los Angeles
California
Stanford University Medical Center
Stanford
California
H Lee Moffitt Cancer Center and Research Institute
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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