Back to resultsTisagenlecleucel vs Blinatumomab or Inotuzumab for Patients With Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia (OBERON)
Primary Purpose
Acute Lymphoblastic Leukemia
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Tisagenlecleucel
Blinatumomab
Inotuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Acute lymphoblastic leukemia, tisagenlecleucel, intouzumab, blinatumomab, CAR-T, CTL019
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent.
- Age ≥ 18 years.
- Subject with CD19-expressing B-ALL.
- Adequate organ function.
Patients considered in any of the following settings are eligible:
- Untreated first or second relapse
- Refractory to primary induction therapy
- Refractory to first salvage therapy or
- Relapse after allogenic stem cell transplant.
Exclusion Criteria:
- Patients presenting with untreated first relapse of ALL more than 24 months after initial diagnosis
- Presence of extra-medullary disease.
- History or presence of clinically relevant CNS pathology, or uncontrolled CNS leukemia.
- History of Veno-occlusive Disease (VOD).
- Active neurological autoimmune or inflammatory disorders.
- Active acute Graft-versus-Host Disease (GvHD), grade 2-4.
Other protocol-defined Inclusion/Exclusion may apply.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tisagenlecleucel arm
Control arm
Arm Description
Patient to receive tisagenlecleucel after optional bridging therapy and lymphodepleting chemotherapy.
blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy
Outcomes
Primary Outcome Measures
Overall Survival (OS)
Time from randomization to death for any reason
Secondary Outcome Measures
Event Free Survival (EFS)
EFS, assessed up to 48 months, is defined as the date from randomization to the earliest of (a) date of death due to any cause, (b) relapse after CR/CRi, or (c) treatment failure, which is defined as failure to achieve remission within 12 weeks of randomization.
Percentage of patients who achieved MRD negative CR/CRi
Percentage of patients who achieved MRD negative CR/CRi at month 3 post randomization
Overall response rate
ORR is defined as the proportion of subjects with best overall response (BOR) of CR or CRi, where the BOR is defined as the best response recorded from randomization until the start of new anticancer therapy or the data cut-off date, whichever is earlier
Duration of response (DOR)
DOR is defined as the duration from the date when the response criteria of CR/CRi is first met to the date of relapse or death due to underlying cancer.
Probability of patients who achieved CR/CRi at month 12
Probability of achieving CR/CRi based on all response assessments between randomization and month 12. This outcome measure will be based on all randomized patients and the assessment will be up to 48 months (from randomization of the first patient until 12 months after the randomization of the last patient).
Prevalence of immunogenecity
Percentage of patients who have anti-tisagenlecleucel antibodies in the serum before randomization
Incidence of immunogenecity
Percentage of patients who develop anti-tisagenlecleucel antibodies in the serum after infusion of tisagenlecleucel
Impact of immunogenicity on clinical response
difference in response between patients with immunogenicity and patients without immunogenicity
Cellular kinetic profile by qPCR
Summary of qPCR detected tisagenlecleucel transgene concentrations
Cellular kinetics profile by flow cytometry
Summary of flow cytometry-detected tisagenlecleucel transgene concentrations
Relationship between dose and response
Relationship between the administered dose of tisagenlecleucel and response to treatment (complete response with or without hematological recovery). This assessment will be done for all patients for up to 48 months.
Relationship between exposure and response
Describe the relationship between the cellular kinetics of tisagenlecleucel overtime and response.
Relationship between dose and cellular kinetic
Describe the relationship between the dose of tisagenlecleucel actually administered and cellular kinetics
EQ-5D-3L
Patient reported outcome measure
EORTC QLQ-30
Patient reported outcome measure
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03628053
Brief Title
Tisagenlecleucel vs Blinatumomab or Inotuzumab for Patients With Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia
Acronym
OBERON
Official Title
Tisagenlecleucel Versus Blinatumomab or Inotuzumab for Adult Patients With Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia: A Randomized Open Label, Multicenter, Phase III Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Novartis is no longer pursuing this study because of planned investigation of novel CAR-T therapies in this patient population.
Study Start Date
June 5, 2020 (Anticipated)
Primary Completion Date
October 8, 2025 (Anticipated)
Study Completion Date
January 7, 2026 (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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This trial aims to compare the benefits and risks of tisagenlecleucel to blinatumomab or inotuzumab in adult patients with relapsed or refractory ALL. This trial investigates tisagenlecleucel as an additional treatment option for this patient population with high unmet medical need.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia
Keywords
Acute lymphoblastic leukemia, tisagenlecleucel, intouzumab, blinatumomab, CAR-T, CTL019
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This is a phase III, open label, multinational, randomized trial. Eligible patients will be randomized 1:1 to Tisagenlecleucel treatment strategy (tisagenlecleucel after optional bridging chemotherapy and lymphodepleting chemotherapy) or control arm treatment strategy (blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy).
The randomization will be performed stratifying for the number of prior salvage therapies (0 vs. 1) and prior allogenic stem cell transplant (yes vs. no).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tisagenlecleucel arm
Arm Type
Experimental
Arm Description
Patient to receive tisagenlecleucel after optional bridging therapy and lymphodepleting chemotherapy.
Arm Title
Control arm
Arm Type
Active Comparator
Arm Description
blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy
Intervention Type
Biological
Intervention Name(s)
Tisagenlecleucel
Other Intervention Name(s)
CTL019, KYMRIAH
Intervention Description
autologous cellular immunotherapy product
Intervention Type
Drug
Intervention Name(s)
Blinatumomab
Other Intervention Name(s)
BLINCYTO
Intervention Description
bispecific CD19-directed CD3 T-cell engager
Intervention Type
Drug
Intervention Name(s)
Inotuzumab
Other Intervention Name(s)
BESPONSA, Inotuzumab ozogamicin
Intervention Description
CD22-directed antibody-drug conjugate
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Time from randomization to death for any reason
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Event Free Survival (EFS)
Description
EFS, assessed up to 48 months, is defined as the date from randomization to the earliest of (a) date of death due to any cause, (b) relapse after CR/CRi, or (c) treatment failure, which is defined as failure to achieve remission within 12 weeks of randomization.
Time Frame
4 years
Title
Percentage of patients who achieved MRD negative CR/CRi
Description
Percentage of patients who achieved MRD negative CR/CRi at month 3 post randomization
Time Frame
4 years
Title
Overall response rate
Description
ORR is defined as the proportion of subjects with best overall response (BOR) of CR or CRi, where the BOR is defined as the best response recorded from randomization until the start of new anticancer therapy or the data cut-off date, whichever is earlier
Time Frame
4 years
Title
Duration of response (DOR)
Description
DOR is defined as the duration from the date when the response criteria of CR/CRi is first met to the date of relapse or death due to underlying cancer.
Time Frame
4 years
Title
Probability of patients who achieved CR/CRi at month 12
Description
Probability of achieving CR/CRi based on all response assessments between randomization and month 12. This outcome measure will be based on all randomized patients and the assessment will be up to 48 months (from randomization of the first patient until 12 months after the randomization of the last patient).
Time Frame
4 years
Title
Prevalence of immunogenecity
Description
Percentage of patients who have anti-tisagenlecleucel antibodies in the serum before randomization
Time Frame
4 years
Title
Incidence of immunogenecity
Description
Percentage of patients who develop anti-tisagenlecleucel antibodies in the serum after infusion of tisagenlecleucel
Time Frame
4 years
Title
Impact of immunogenicity on clinical response
Description
difference in response between patients with immunogenicity and patients without immunogenicity
Time Frame
4 years
Title
Cellular kinetic profile by qPCR
Description
Summary of qPCR detected tisagenlecleucel transgene concentrations
Time Frame
4 years
Title
Cellular kinetics profile by flow cytometry
Description
Summary of flow cytometry-detected tisagenlecleucel transgene concentrations
Time Frame
4 years
Title
Relationship between dose and response
Description
Relationship between the administered dose of tisagenlecleucel and response to treatment (complete response with or without hematological recovery). This assessment will be done for all patients for up to 48 months.
Time Frame
4 years
Title
Relationship between exposure and response
Description
Describe the relationship between the cellular kinetics of tisagenlecleucel overtime and response.
Time Frame
4 years
Title
Relationship between dose and cellular kinetic
Description
Describe the relationship between the dose of tisagenlecleucel actually administered and cellular kinetics
Time Frame
4 years
Title
EQ-5D-3L
Description
Patient reported outcome measure
Time Frame
4 years
Title
EORTC QLQ-30
Description
Patient reported outcome measure
Time Frame
4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent.
Age ≥ 18 years.
Subject with CD19-expressing B-ALL.
Adequate organ function.
Patients considered in any of the following settings are eligible:
Untreated first or second relapse
Refractory to primary induction therapy
Refractory to first salvage therapy or
Relapse after allogenic stem cell transplant.
Exclusion Criteria:
Patients presenting with untreated first relapse of ALL more than 24 months after initial diagnosis
Presence of extra-medullary disease.
History or presence of clinically relevant CNS pathology, or uncontrolled CNS leukemia.
History of Veno-occlusive Disease (VOD).
Active neurological autoimmune or inflammatory disorders.
Active acute Graft-versus-Host Disease (GvHD), grade 2-4.
Other protocol-defined Inclusion/Exclusion may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com
Learn more about this trial
Tisagenlecleucel vs Blinatumomab or Inotuzumab for Patients With Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia
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