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Study of Out of Specification for Tisagenlecleucel

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04094311
Collaborator
(none)
42
Enrollment
42
Locations
3
Arms
40.7
Anticipated Duration (Months)
1
Patient Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Biological: CTL019
 Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
42 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Nov 21, 2019
Anticipated Primary Completion Date :
Apr 14, 2023
Anticipated Study Completion Date :
Apr 14, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group A: pALL

Pediatric/young adult patients with r/r pALL who meet the indication in the Health Authority-approved CTL019 package insert in the respective country/region whose final manufactured product is OOS for commercial release, but it is considered that the benefit-risk profile may remain favorable and the usual expected benefits of infusing such a product outweigh the potential risks for the patient.

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

    		•
    Experimental: Group B: r/r LBCL

    Adult patients with r/r LBCL including DLBCL not otherwise specified, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma, that is consistent with the Health Authority-approved indication in the package insert for CTL019 in the respective country/region whose final manufactured product is OOS for commercial release, but it is considered that the benefit-risk profile may remain favorable and the usual expected benefits of infusing such a product outweigh the potential risks for the patient.

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

    		•
    Experimental: Group C: r/r NHL

    Adult patients with r/r NHL in consistent with the Health Authority approved indication in the package insert for CTL019 in Japan whose final manufactured product is OOS for commercial release, but it is considered that the benefit-risk profile may remain favorable and the usual expected benefits of infusing such a product outweigh the potential risks for the patient.

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of participants with Adverse Events (AEs) [From Screening up to 3 months for Part 1 and 1 day for Part 2]

      Percentage of participants with Serious AEs (SAEs) and non-SAEs

    Secondary Outcome Measures

    1. Part 1: Overall Remission Rate in Group A (pALL) [Up to 3 months]

      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).

    2. Part 1: Overall Response Rate in Group B (LBCL) [Up to 3 months]

      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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Hamilton Ontario Canada L8V 5C2
    2 Novartis Investigative Site Ottawa Ontario Canada K1H 8L6
    3 Novartis Investigative Site Toronto Ontario Canada M5G 1X8
    4 Novartis Investigative Site Toronto Ontario Canada M5G 2M9
    5 Novartis Investigative Site Montreal Quebec Canada H1T 2M4
    6 Novartis Investigative Site Quebec Canada G1R 2J6
    7 Novartis Investigative Site Nagoya Aichi Japan 466 8560
    8 Novartis Investigative Site Fukuoka city Fukuoka Japan 812-8582
    9 Novartis Investigative Site Gifu-city Gifu Japan 501-1194
    10 Novartis Investigative Site Hiroshima City Hiroshima Japan 734-8551
    11 Novartis Investigative Site Sapporo city Hokkaido Japan 060 8648
    12 Novartis Investigative Site Kobe-city Hyogo Japan 650-0047
    13 Novartis Investigative Site Nishinomiya Hyogo Japan 663 8501
    14 Novartis Investigative Site Tsukuba city Ibaraki Japan 305-8576
    15 Novartis Investigative Site Kanazawa-city Ishikawa Japan 920-8641
    16 Novartis Investigative Site Kita-gun Kagawa Japan 761-0793
    17 Novartis Investigative Site Yokohama-city Kanagawa Japan 236-0004
    18 Novartis Investigative Site Kyoto-city Kyoto Japan 602-8566
    19 Novartis Investigative Site Tsu-city Mie Japan 514-8507
    20 Novartis Investigative Site Sendai city Miyagi Japan 980 8574
    21 Novartis Investigative Site Matsumoto-city Nagano Japan 390-8621
    22 Novartis Investigative Site Nagasaki-city Nagasaki Japan 852-8501
    23 Novartis Investigative Site Kurashiki-city Okayama Japan 710-8602
    24 Novartis Investigative Site Okayama-city Okayama Japan 700-8558
    25 Novartis Investigative Site Osaka Sayama Osaka Japan 589 8511
    26 Novartis Investigative Site Osaka-city Osaka Japan 541-8567
    27 Novartis Investigative Site Osaka-city Osaka Japan 543-8555
    28 Novartis Investigative Site Suita city Osaka Japan 565 0871
    29 Novartis Investigative Site Hamamatsu-city Shizuoka Japan 431-3192
    30 Novartis Investigative Site Bunkyo ku Tokyo Japan 113 8655
    31 Novartis Investigative Site Bunkyo ku Tokyo Japan 113-8431
    32 Novartis Investigative Site Bunkyo ku Tokyo Japan 113-8677
    33 Novartis Investigative Site Bunkyo-ku Tokyo Japan 113-8519
    34 Novartis Investigative Site Chuo ku Tokyo Japan 104 0045
    35 Novartis Investigative Site Minato-ku Tokyo Japan 105-8471
    36 Novartis Investigative Site Setagaya-ku Tokyo Japan 157-8535
    37 Novartis Investigative Site Shinjuku-ku Tokyo Japan 160 8582
    38 Novartis Investigative Site Chiba Japan 260 8677
    39 Novartis Investigative Site Kyoto Japan 606 8507
    40 Novartis Investigative Site Niigata Japan 951 8520
    41 Novartis Investigative Site Osaka Japan 545-8586
    42 Novartis Investigative Site Saitama Japan 330 8777

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT04094311
    Other Study ID Numbers:
    • CCTL019B2302
    First Posted:
    Sep 18, 2019
    Last Update Posted:
    Aug 8, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Novartis Pharmaceuticals
    out of specification
    tisagenlecleucel
    acute lymphoblastic leukemia
    large B-cell lymphoma
    relapsed/refractory
    pediatric
    young adult patients
    Additional relevant MeSH terms:
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid
    Lymphoma, B-Cell
    Lymphoma, Large B-Cell, Diffuse

    Study Results

    No Results Posted as of Aug 8, 2022