Back to resultsStudy of Out of Specification for Tisagenlecleucel
Primary Purpose
B-cell Acute Lymphoblastic Leukemia, Diffuse Large B-cell Lymphoma
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
CTL019
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Acute Lymphoblastic Leukemia focused on measuring out of specification, tisagenlecleucel, acute lymphoblastic leukemia, large B-cell lymphoma, relapsed/refractory, pediatric, young adult patients
Eligibility Criteria
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.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Group A: pALL
Group B: r/r LBCL
Group C: r/r NHL
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
Percentage of participants with Adverse Events (AEs)
Percentage of participants with Serious AEs (SAEs) and non-SAEs
Secondary Outcome Measures
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).
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).
Full Information
NCT ID
NCT04094311
First Posted
September 16, 2019
Last Updated
September 6, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04094311
Brief Title
Study of Out of Specification for Tisagenlecleucel
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 21, 2019 (Actual)
Primary Completion Date
December 29, 2023 (Anticipated)
Study Completion Date
December 29, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
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
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Acute Lymphoblastic Leukemia, Diffuse Large B-cell Lymphoma
Keywords
out of specification, tisagenlecleucel, acute lymphoblastic leukemia, large B-cell lymphoma, relapsed/refractory, pediatric, young adult patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A: pALL
Arm Type
Experimental
Arm Description
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.
Arm Title
Group B: r/r LBCL
Arm Type
Experimental
Arm Description
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.
Arm Title
Group C: r/r NHL
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CTL019
Other Intervention Name(s)
Tisagenlecleucel
Intervention Description
A single intravenous (i.v.) infusion of CAR-positive viable T cells.
Primary Outcome Measure Information:
Title
Percentage of participants with Adverse Events (AEs)
Description
Percentage of participants with Serious AEs (SAEs) and non-SAEs
Time Frame
From Screening up to 3 months for Part 1 and 1 day for Part 2
Secondary Outcome Measure Information:
Title
Part 1: Overall Remission Rate in Group A (pALL)
Description
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).
Time Frame
Up to 3 months
Title
Part 1: Overall Response Rate in Group B (LBCL)
Description
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).
Time Frame
Up to 3 months
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Email
Novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+81337978748
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Individual Site Status
Completed
Facility Name
Novartis Investigative Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Withdrawn
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Individual Site Status
Completed
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Completed
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Individual Site Status
Withdrawn
Facility Name
Novartis Investigative Site
City
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada
Individual Site Status
Withdrawn
Facility Name
Novartis Investigative Site
City
Nagoya-city
State/Province
Aichi
ZIP/Postal Code
467-8602
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466 8560
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Toon-city
State/Province
Ehime
ZIP/Postal Code
791-0295
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Fukuoka city
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Gifu-city
State/Province
Gifu
ZIP/Postal Code
501-1194
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sapporo city
State/Province
Hokkaido
ZIP/Postal Code
060 8648
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8543
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kobe-city
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663 8501
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tsukuba city
State/Province
Ibaraki
ZIP/Postal Code
305-8576
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kanazawa-city
State/Province
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kita-gun
State/Province
Kagawa
ZIP/Postal Code
761-0793
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Yokohama-city
State/Province
Kanagawa
ZIP/Postal Code
236-0004
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kumamoto City
State/Province
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kyoto-city
State/Province
Kyoto
ZIP/Postal Code
602-8566
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tsu-city
State/Province
Mie
ZIP/Postal Code
514-8507
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sendai city
State/Province
Miyagi
ZIP/Postal Code
980 8574
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Matsumoto-city
State/Province
Nagano
ZIP/Postal Code
390-8621
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nagasaki-city
State/Province
Nagasaki
ZIP/Postal Code
852-8501
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Yufu
State/Province
Oita
ZIP/Postal Code
879-5593
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kurashiki-city
State/Province
Okayama
ZIP/Postal Code
710-8602
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Okayama-city
State/Province
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Izumi-city
State/Province
Osaka
ZIP/Postal Code
594-1101
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Osaka Sayama
State/Province
Osaka
ZIP/Postal Code
589 8511
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Osaka-city
State/Province
Osaka
ZIP/Postal Code
541-8567
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Osaka-city
State/Province
Osaka
ZIP/Postal Code
543-8555
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Suita
State/Province
Osaka
ZIP/Postal Code
565 0871
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Izumo-city
State/Province
Shimane
ZIP/Postal Code
693 8501
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hamamatsu-city
State/Province
Shizuoka
ZIP/Postal Code
431-3192
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bunkyo ku
State/Province
Tokyo
ZIP/Postal Code
113 8655
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bunkyo ku
State/Province
Tokyo
ZIP/Postal Code
113-8431
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bunkyo ku
State/Province
Tokyo
ZIP/Postal Code
113-8677
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8519
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Chuo ku
State/Province
Tokyo
ZIP/Postal Code
104 0045
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Minato-ku
State/Province
Tokyo
ZIP/Postal Code
105-8471
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Setagaya-ku
State/Province
Tokyo
ZIP/Postal Code
157-8535
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160 8582
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Chiba
ZIP/Postal Code
260 8677
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hiroshima
ZIP/Postal Code
734-8551
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kyoto
ZIP/Postal Code
606 8507
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Niigata
ZIP/Postal Code
951 8520
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Osaka
ZIP/Postal Code
545-8586
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Saitama
ZIP/Postal Code
330 8777
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Wakayama
ZIP/Postal Code
641-8510
Country
Japan
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Learn more about this trial
Study of Out of Specification for Tisagenlecleucel
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