Chronic Lymphocytic Leukemia Clinical Trial

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

Summary

This is a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of autologous T cells genetically engineered with a CD19-specific chimeric antigen receptor (CAR) and manufactured with a new process. CAR-T cells will be investigated in combination with ibrutinib in leukemia-cll/" >chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and as single agent in diffuse large B-cell lymphoma (DLBCL) and in adult acute lymphoblastic leukemia (ALL).

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Full Description

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.

View Eligibility Criteria

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 is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 1

Estimated Enrollment:

225

Study ID:

NCT03960840

Recruitment Status:

Recruiting

Sponsor:

Novartis Pharmaceuticals

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There are 40 Locations for this study

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University Of California LA UCLA Hematology Oncology
Los Angeles California, 90095, United States More Info
Elizabeth Benkert
Contact
310-794-6500
[email protected]
Patricia Young
Principal Investigator
Stanford University Medical Center
Stanford California, 94305, United States More Info
Kendall Levine
Contact
650-725-0701
[email protected]
Saurabh Dahiya
Principal Investigator
H Lee Moffitt Cancer Center and Research Institute .
Tampa Florida, 33612, United States More Info
Brian James
Contact
888-663-3488
[email protected]
Julio Chavez
Principal Investigator
Northside Hospital .
Atlanta Georgia, 30342, United States More Info
Adriane Strong
Contact
404-255-1930
[email protected]
Scott D. Solomon
Principal Investigator
Northwestern University Northwestern Memorial Hospital Trans
Chicago Illinois, 60611, United States More Info
Holly Roberta Krieg
Contact
[email protected]
Shira Dinner
Principal Investigator
Uni of Chi Medi Ctr Hema and Onco
Chicago Illinois, 60637, United States More Info
Bruna Vieira
Contact
773-834-8980
[email protected]
Peter Riedell
Principal Investigator
University of Kansas Cancer Center SC - CTL019C2201
Westwood Kansas, 66205, United States More Info
Jessie Lamphier
Contact
913-588-6029
[email protected]
Leyla Shune
Principal Investigator
Mass Gen Hosp Cancer Center .
Boston Massachusetts, 02114, United States More Info
Kathryn Cioffi
Contact
617-726-2000
[email protected]
Matthew Frigault
Principal Investigator
Montefiore Medical Center .
Bronx New York, 10461, United States More Info
Aradhika Dhawan
Contact
718-920-2680
[email protected]
Dennis Cooper
Principal Investigator
University of Pennsylvania Clinical Perelman Center for Adv Med
Philadelphia Pennsylvania, 19104, United States More Info
Stella Krawiec
Contact
215-615-6721
[email protected]
Noelle Frey
Principal Investigator
Sarah Cannon Research Institute Drug Ship - 4
Nashville Tennessee, 37203, United States More Info
Lauren Cary
Contact
615-329-7274
[email protected]
Ian W. Flinn
Principal Investigator
Sarah Cannon Research Institute Methodist Hospital
Nashville Tennessee, 37221, United States More Info
Tiarra Walker
Contact
[email protected]
Paul Shaughnessy
Principal Investigator
St Davids South Austin Medical Ctr
Austin Texas, 78704, United States More Info
Amy Hammack
Contact
512-447-2211
[email protected]
Aravind Ramakrishnan
Principal Investigator
Uni of TX MD Anderson Cancer Cntr
Houston Texas, 77030, United States More Info
Priscilla Cardenas
Contact
713-792-2921
[email protected]
Jason Westin
Principal Investigator
Medical College of Wisconsin Main Centre
Milwaukee Wisconsin, 53226, United States More Info
Jessica Neumann
Contact
414-805-4600
[email protected]
Nirav Shah
Principal Investigator
Novartis Investigative Site
Melbourne Victoria, 3000, Australia
Novartis Investigative Site
Melbourne Victoria, 3004, Australia
Novartis Investigative Site
Wien , A-109, Austria
Novartis Investigative Site
Marseille , 13273, France
Novartis Investigative Site
Paris 10 , 75475, France
Novartis Investigative Site
Pierre Benite , 69495, France
Novartis Investigative Site
Essen , 45147, Germany
Novartis Investigative Site
Frankfurt , 60590, Germany
Novartis Investigative Site
Koeln , 50937, Germany
Novartis Investigative Site
Bergamo BG, 24128, Italy
Novartis Investigative Site
Bologna BO, 40138, Italy
Novartis Investigative Site
Milano MI, 20132, Italy
Novartis Investigative Site
Rozzano MI, 20089, Italy
Novartis Investigative Site
Fukuoka city Fukuoka, 812-8, Japan
Novartis Investigative Site
Sapporo city Hokkaido, 060 8, Japan
Novartis Investigative Site
Bunkyo ku Tokyo, 113-8, Japan
Novartis Investigative Site
Cordoba Andalucia, 14004, Spain
Novartis Investigative Site
Sevilla Andalucia, 41013, Spain
Novartis Investigative Site
Salamanca Castilla Y Leon, 37007, Spain
Novartis Investigative Site
Badalona Catalunya, 08916, Spain
Novartis Investigative Site
Barcelona Catalunya, 08035, Spain
Novartis Investigative Site
Valencia Comunidad Valenciana, 46010, Spain
Novartis Investigative Site
Barcelona , 08041, Spain
Novartis Investigative Site
Madrid , 28009, Spain
Novartis Investigative Site
Madrid , 28041, Spain

How clear is this clinincal trial information?

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 1

Estimated Enrollment:

225

Study ID:

NCT03960840

Recruitment Status:

Recruiting

Sponsor:


Novartis Pharmaceuticals

How clear is this clinincal trial information?

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