Study of Out of Specification for Tisagenlecleucel

Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

A Phase IIIb Study of the Safety and Efficacy of Tisagenlecleucel Out of Specification for Commercial Release in Patients Who Are Consistent With the Label Indication

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04094311
• Other study ID #: CCTL019B2302
• Status: Recruiting
• Phase: Phase 3
• Start date: November 21, 2019
• Est. completion date: April 18, 2025

Study information

• Verified date: January 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +41613241111
• Email: Novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety of tisagenlecleucel that is out of specification( OOS) for release as commercial product. Specifically, this study will evaluate the safety of CTL019 in the patients treated within the approved label by Japan Health Authority in Part 2. Only for Part 1, in addition to safety, key efficacy of CTL019 will also be evaluated.

Description:

This is a single-arm, open-label, multicenter, interventional Phase IIIb study in pediatric/young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (pALL) and adult patients with r/r large B-cell lymphoma (LBCL) including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B cell lymphoma, and DLBCL arising from follicular lymphoma for Part 1 and and r/r ALL and r/r non-Hodgkin's lymphomas (NHL) for Part 2 Patients whose final manufactured tisagenlecleucel patient-specific batch does not meet the approved local commercial release specifications are eligible for inclusion. Each case will be individually assessed and approved by the Novartis manufacturing facility and the Novartis global medical team (including Patient Safety). Following a single infusion of CTL019, the patient will be followed for 3 months for Part 1, and 1 day for Part 2.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 18, 2025
• Est. primary completion date: April 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Key inclusion criteria:

• Signed informed consent/assent must be obtained for this study prior to participation in the study.
• Patients for whom the final manufactured tisagenlecleucel product does not meet the commercial release specifications.
• Not excluded from commercial manufacturing under the Health Authority-approved tisagenlecleucel prescribing information for their respective country/region.
• OOS material has not been deemed to pose an undue safety risk to the patient.
• Patient is suffering from a serious or life-threatening disease or condition.
• Repeat leukapheresis is not clinically appropriate per the investigator assessment. Key exclusion criteria: For part 1, patients meeting any of the following criteria are not eligible for inclusion

in this study:

• Human immunodeficience virus (HIV) positive patients.
• Patients with active replication of Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
• Patients with primary central nervous system (CNS) lymphoma.
• History of hypersensitivity to any drugs or metabolites of similar chemical classes as tisagenlecleucel.
• Uncontrolled active infection or inflammation.
• Any medical condition identified by the investigator that may impact the assessment of the safety or efficacy outcomes in relation to study treatment.
• Pregnant or nursing (lactating) women. For part 2, exclusion criteria are not set; however, administration should be performed in accordance with the latest versions of the package insert of CTL019.

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia
• Diffuse Large B-cell Lymphoma
• Leukemia, Lymphoid
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• CTL019
A single intravenous (i.v.) infusion of CAR-positive viable T cells.

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Japan	Novartis Investigative Site	Aomori
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Gifu-city	Gifu
Japan	Novartis Investigative Site	Hamamatsu-city	Shizuoka
Japan	Novartis Investigative Site	Hiroshima
Japan	Novartis Investigative Site	Izumi-city	Osaka
Japan	Novartis Investigative Site	Izumisano-city	Osaka
Japan	Novartis Investigative Site	Izumo-city	Shimane
Japan	Novartis Investigative Site	Kanazawa-city	Ishikawa
Japan	Novartis Investigative Site	Kita-gun	Kagawa
Japan	Novartis Investigative Site	Kobe-city	Hyogo
Japan	Novartis Investigative Site	Kumamoto City	Kumamoto
Japan	Novartis Investigative Site	Kurashiki-city	Okayama
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Matsumoto	Nagano
Japan	Novartis Investigative Site	Minato-ku	Tokyo
Japan	Novartis Investigative Site	Nagasaki-city	Nagasaki
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Niigata
Japan	Novartis Investigative Site	Nishinomiya	Hyogo
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka Sayama	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Saitama
Japan	Novartis Investigative Site	Sapporo	Hokkaido
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Sendai city	Miyagi
Japan	Novartis Investigative Site	Setagaya-ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Suita	Osaka
Japan	Novartis Investigative Site	Toon city	Ehime
Japan	Novartis Investigative Site	Tsu-city	Mie
Japan	Novartis Investigative Site	Tsukuba city	Ibaraki
Japan	Novartis Investigative Site	Wakayama
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Japan	Novartis Investigative Site	Yufu	Oita

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Canada,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with Adverse Events (AEs)	Percentage of participants with Serious AEs (SAEs) and non-SAEs	From Screening up to 3 months for Part 1 and 1 day for Part 2
Secondary	Part 1: Overall Remission Rate in Group A (pALL)	Overall Remission Rate is defined as the percentage of participants wiho achieve a complete remission (CR) and CR with incomplete blood count recovery (CRi) within 3 months following infusion of CTL019 as determined by the local investigator assessment for participants in group A (part 1).	Up to 3 months
Secondary	Part 1: Overall Response Rate in Group B (LBCL)	ORR is defined as the percentage of patients who achieve a domplete response and partial response within 3 months following infusion of CTL019 as determined by the local investigator assessment for participants in group B (part 1).	Up to 3 months