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

NCT03960840 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CYTB323A12101
• Study Type: interventional
• Target: 217
• Locations: 7 countries
• Sites: 36

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).

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Large B-cell Lymphoma; Acute Lymphoblastic Leukemia; Large B-cell Lymphoma

Keywords

CAR-T; Ibrutinib; CLL; DLBCL; ALL; BLRM; YTB323; Rapcabtagene autoleucel

Outcome Measures

Primary Outcomes (5)

• 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

  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)

  24 months

Secondary Outcomes (29)

• Phase 1: Complete Response (CR)/Partial Response (CR) in CLL/SLL

  24 months

• Phase 1: BOR of CR/PR per Lugano criteria in 3L+ DLBCL

  24 months

• Phase 1: Duration of response (DOR) in CLL/SLL and 3L+ DLBCL

  24 months

• Phase 1: BOR in ALL as assessed by an Independent Review Committee (IRC)

  month 3

• Phase 1: DOR in ALL as assessed by an Independent Review Committee

  24 months

Study Arms (4)

CLL/SLL

EXPERIMENTAL

Dose escalation of rapcabtagene autoleucel in combination with ibrutinib

Biological: Rapcabtagene autoleucel single agent; Drug: Ibrutinib

3L+ DLBCL

EXPERIMENTAL

Dose escalation and expansion of rapcabtagene autoleucel single agent in 3L+ DLBCL

Biological: Rapcabtagene autoleucel single agent

Adult ALL

EXPERIMENTAL

Dose escalation of rapcabtagene autoleucel single agent in adult ALL

Biological: Rapcabtagene autoleucel single agent

1L HR LBCL

EXPERIMENTAL

Rapcabtagene autoleucel single agent in 1L HR LBCL

Biological: Rapcabtagene autoleucel single agent

Interventions

Ibrutinib DRUG

Tablets or capsules for oral daily use

CLL/SLL

Rapcabtagene autoleucel single agent BIOLOGICAL

Single infusion of rapcabtagene autoleucel

1L HR LBCL; 3L+ DLBCL; Adult ALL; CLL/SLL

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• L 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (38)

University of California LA

Los Angeles, California, 90095, United States

Location

Stanford University Medical Center

Stanford, California, 94305-5826, United States

Location

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Uni of Chi Medi Ctr Hema and Onco

Chicago, Illinois, 60637, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Mass Gen Hosp Cancer Center

Boston, Massachusetts, 02114, United States

Location

University of Pennsylvania Clinical

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37221, United States

Location

St Davids South Austin Medical Ctr

Austin, Texas, 78704, United States

Location

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Paris, 75475, France

Location

Novartis Investigative Site

Pierre-Bénite, 69495, France

Location

Novartis Investigative Site

Rennes, 35033, France

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

Location

Novartis Investigative Site

Leipzig, Saxony, 04103, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Bergamo, BG, 24127, Italy

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Sapporo, Hokkaido, 060-8648, Japan

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 1138677, Japan

Location

Novartis Investigative Site

Fukuoka, 8128582, Japan

Location

Novartis Investigative Site

Badalona, Barcelona, 08916, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Barcelona, 08041, Spain

Location

Novartis Investigative Site

Córdoba, 14004, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Salamanca, 37007, Spain

Location

Novartis Investigative Site

Seville, 41013, Spain

Location

Novartis Investigative Site

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 23, 2019
• Study Start: June 26, 2019
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); DE (3); FR (4); IT (3); AU (1); ES (10); JP (3)