Last Update: May 03, 2024
Phase I/II, Open Label, Multicenter Study of Rapcabtagene Autoleucel in Adult Patients With CLL/SLL, 3L+ DLBCL, ALL and 1L HR LBCL
ClinicalTrials.gov Identifier:
Novartis Reference Number:CYTB323A12101
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

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). This clinical trial is phase I/II open label, multi-center study of rapcabtagene
autoleucel.

The Phase I part of the study comprises three independent treatment arms:

- Rapcabtagene autoleucel in combination with ibrutinib in adult CLL/SLL participants
with SD or PR after at least 6 months of second or subsequent line ibrutinib
therapy. As of 05-May-2021, this arm had completed enrollment.

- Rapcabtagene autoleucel single agent in adult DLBCL participants having failed two
or more lines of chemotherapy and either having progressed (or relapsed) after
autologous HSCT or being ineligible for or not consenting to the procedure.

- Rapcabtagene autoleucel single agent in adult relapsed/refractory ALL participants

The Phase II part of the study comprises two independent cohorts:

- Rapcabtagene autoleucel single agent in adult 3L + DLBCL participants having failed
two or more lines of chemoimmunotherapy and either having progressed (or relapsed)
after autologous HSCT or being ineligible for or not consenting to the procedure.
This is an extension of the Phase I r/r DLBCL treatment arm to support Phase II
objectives

- Rapcabtagene autoleucel single agent in newly diagnosed, adult 1L HR LBCL
participants defined as IPI 3-5 and/or DH/TH disease who have completed 2 cycles of
CIT and have a response of PR/SD (with a Deauville score of 4-5).

In the Phase I part of the trial, the 3L+ DLBCL and ALL arms consist of two parts: a dose
escalation part to evaluate feasibility, characterize safety and identify the recommended
dose (RD) of rapcabtagene autoleucel, and a dose expansion part to further characterize
safety, study rapcabtagene autoleucel cellular kinetics and assess preliminary antitumor
activity. Once the RD of rapcabtagene autoleucel is determined for each arm, the
corresponding expansion part will commence.

In the Phase II part of the trial, approximately 70 additional participants will be
enrolled in a 3L+ DLBCL cohort treated at the recommended dose (RD). Including the 3L+
DLBCL participants who were treated at the RD from the Phase I part, it is planned to
have in total a cohort of approximately 100 participants included in the primary efficacy
analysis based on the efficacy analysis set. In addition, a separate cohort in 1LHR LBCL
will be included, with approximately 40 participants planned for the primary efficacy
analysis based on the efficacy analysis set.

Participants will be followed under the current treatment protocol for safety and
efficacy within this trial for a minimum of 2 years before being transferred to the
long-term follow-up trial. Once the study is complete, participants will be enrolled in a
post-study long term follow-up for lentiviral vector safety for up to 15 years. This
post-study long term follow-up for lentiviral vector safety will continue under a
separate destination protocol.

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Diffuse Large B-cell Lymphoma, Acute Lymphoblastic Leukemia, Large B-cell Lymphoma
Phase1, Phase2
Recruiting
225
Jun 26, 2019
Jun 30, 2027
All
18 Years - (Adult, Older Adult)

Interventions

Drug

Ibrutinib

Tablets or capsules for oral daily use
Biological

Rapcabtagene autoleucel single agent

Single infusion of rapcabtagene autoleucel

Eligibility Criteria

Inclusion Criteria:

- 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)

- 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/THL)

- 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
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 CNS involvement by malignancy

- Targeted small molecule or kinase inhibitor within 2 weeks from leukapheresis

Other protocol-defined inclusion/exclusion may apply.

Study Location

Novartis Investigative Site

Recruiting

Melbourne,Victoria,3004,Australia

Novartis Investigative Site

Recruiting

Melbourne,Victoria,3000,Australia

Novartis Investigative Site

Recruiting

Wien,A-1090,Austria

Novartis Investigative Site

Recruiting

Paris 10,75475,France

Novartis Investigative Site

Recruiting

Pierre Benite,69495,France

Novartis Investigative Site

Recruiting

Marseille,13273,France

Novartis Investigative Site

Recruiting

Koeln,50937,Germany

Novartis Investigative Site

Recruiting

Essen,45147,Germany

Novartis Investigative Site

Recruiting

Frankfurt,60590,Germany

Novartis Investigative Site

Recruiting

Bergamo,BG,24128,Italy

Novartis Investigative Site

Recruiting

Milano,MI,20132,Italy

Novartis Investigative Site

Recruiting

Bologna,BO,40138,Italy

Novartis Investigative Site

Recruiting

Rozzano,MI,20089,Italy

Novartis Investigative Site

Recruiting

Fukuoka city,Fukuoka,812-8582,Japan

Novartis Investigative Site

Recruiting

Bunkyo ku,Tokyo,113-8677,Japan

Novartis Investigative Site

Recruiting

Sapporo city,Hokkaido,060 8648,Japan

Novartis Investigative Site

Recruiting

Barcelona,08041,Spain

Novartis Investigative Site

Recruiting

Sevilla,Andalucia,41013,Spain

Novartis Investigative Site

Recruiting

Valencia,Comunidad Valenciana,46010,Spain

Novartis Investigative Site

Recruiting

Madrid,28009,Spain

Novartis Investigative Site

Recruiting

Madrid,28041,Spain

Novartis Investigative Site

Recruiting

Cordoba,Andalucia,14004,Spain

Novartis Investigative Site

Recruiting

Badalona,Catalunya,08916,Spain

Novartis Investigative Site

Recruiting

Salamanca,Castilla Y Leon,37007,Spain

Novartis Investigative Site

Recruiting

Barcelona,Catalunya,08035,Spain

Stanford University Medical Center

Recruiting

Stanford,California,94305-5826,United States

Medical College of Wisconsin Main Centre

Recruiting

Milwaukee,Wisconsin,53226,United States

Montefiore Medical Center .

Recruiting

Bronx,New York,10461,United States

Uni of Chi Medi Ctr Hema and Onco

Recruiting

Chicago,Illinois,60637,United States

Northside Hospital .

Recruiting

Atlanta,Georgia,30342,United States

Uni of TX MD Anderson Cancer Cntr

Recruiting

Houston,Texas,77030,United States

Northwestern University Northwestern Memorial Hospital Trans

Recruiting

Chicago,Illinois,60611,United States

University Of California LA UCLA Hematology Oncology

Recruiting

Los Angeles,California,90095,United States

Sarah Cannon Research Institute Drug Ship - 4

Recruiting

Nashville,Tennessee,37203,United States

University of Kansas Cancer Center SC - CTL019C2201

Recruiting

Westwood,Kansas,66205,United States

Sarah Cannon Research Institute Methodist Hospital

Recruiting

Nashville,Tennessee,37221,United States

H Lee Moffitt Cancer Center and Research Institute .

Recruiting

Tampa,Florida,33612,United States

University of Pennsylvania Clinical Perelman Center for Adv Med

Recruiting

Philadelphia,Pennsylvania,19104,United States

St Davids South Austin Medical Ctr

Recruiting

Austin,Texas,78704,United States

Mass Gen Hosp Cancer Center .

Recruiting

Boston,Massachusetts,02114,United States

Worldwide Contacts

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Novartis Pharmaceuticals

Novartis Pharmaceuticals