Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL

About

Brief 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).

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1/Phase 2

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

100 Years

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.