Acute Lymphoblastic LeukemiaPhase 3OBERONNCT03628053
Tisagenlecleucel vs Blinatumomab or Inotuzumab for Patients With Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia
A Phase 3 study testing Tisagenlecleucel, Blinatumomab and Inotuzumab in people with Acute Lymphoblastic Leukemia, run by Novartis Pharmaceuticals.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- Tisagenlecleucel, Blinatumomab and Inotuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 5 Jun 2020to 7 Jan 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Refractory to primary induction therapy
- Refractory to first salvage therapy or
- Relapse after allogenic stem cell transplant.
Who cannot join
- 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.
About this study
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
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.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- Tisagenlecleucel, Blinatumomab, Inotuzumab
- Keywords
- Acute lymphoblastic leukemia, tisagenlecleucel, intouzumab, blinatumomab, CAR-T, CTL019
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TisagenlecleucelBiological
Also called CTL019, KYMRIAH
autologous cellular immunotherapy product
BlinatumomabDrug
Also called BLINCYTO
bispecific CD19-directed CD3 T-cell engager
InotuzumabDrug
Also called BESPONSA, Inotuzumab ozogamicin
CD22-directed antibody-drug conjugate
| Study group | Role | What they receive |
|---|---|---|
| Tisagenlecleucel arm | Experimental | Patient to receive tisagenlecleucel after optional bridging therapy and lymphodepleting chemotherapy. Receives: Biological: Tisagenlecleucel |
| Control arm | Active comparator | blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy Receives: Drug: Blinatumomab; Drug: Inotuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Time from randomization to death for any reason
Measured: 4 years
Secondary outcomes (15)
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.
Measured: 4 years
Percentage of patients who achieved MRD negative CR/CRi
Percentage of patients who achieved MRD negative CR/CRi at month 3 post randomization
Measured: 4 years
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
Measured: 4 years
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.
Measured: 4 years
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).
Measured: 4 years
Prevalence of immunogenecity
Percentage of patients who have anti-tisagenlecleucel antibodies in the serum before randomization
Measured: 4 years
Incidence of immunogenecity
Percentage of patients who develop anti-tisagenlecleucel antibodies in the serum after infusion of tisagenlecleucel
Measured: 4 years
Impact of immunogenicity on clinical response
difference in response between patients with immunogenicity and patients without immunogenicity
Measured: 4 years
Cellular kinetic profile by qPCR
Summary of qPCR detected tisagenlecleucel transgene concentrations
Measured: 4 years
Cellular kinetics profile by flow cytometry
Summary of flow cytometry-detected tisagenlecleucel transgene concentrations
Measured: 4 years
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.
Measured: 4 years
Relationship between exposure and response
Describe the relationship between the cellular kinetics of tisagenlecleucel overtime and response.
Measured: 4 years
Relationship between dose and cellular kinetic
Describe the relationship between the dose of tisagenlecleucel actually administered and cellular kinetics
Measured: 4 years
EQ-5D-3L
Patient reported outcome measure
Measured: 4 years
EORTC QLQ-30
Patient reported outcome measure
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2018
- Study start5 Jun 2020 (estimated)
- Primary completion8 Oct 2025 (estimated)
- Study completion7 Jan 2026 (estimated)
Why it stopped: Novartis is no longer pursuing this study because of planned investigation of novel CAR-T therapies in this patient population.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03628053
- Sponsor's protocol ID
- CCTL019I2301
- Acronym
- OBERON
- Status last verified
- Jul 2020
- First submitted
- 28 Jun 2018
- Last updated
- 9 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03628053
- Acronym / sponsor ID
- OBERON / CCTL019I2301
- Conditions
- Acute Lymphoblastic Leukemia
- Keywords
- Acute lymphoblastic leukemia, tisagenlecleucel, intouzumab, blinatumomab, CAR-T, CTL019
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Novartis is no longer pursuing this study because of planned investigation of novel CAR-T therapies in this patient population.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 5 Jun 2020 (estimated)
- Primary completion
- 8 Oct 2025 (estimated)
- Study completion
- 7 Jan 2026 (estimated)
- First posted
- 14 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Tisagenlecleucel arm | Experimental | Biological: TisagenlecleucelPatient to receive tisagenlecleucel after optional bridging therapy and lymphodepleting chemotherapy. |
| Control arm | Active comparator | Drug: Blinatumomab, Drug: Inotuzumabblinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TisagenlecleucelAlso: CTL019, KYMRIAHautologous cellular immunotherapy product | Biological | Tisagenlecleucel arm |
| BlinatumomabAlso: BLINCYTObispecific CD19-directed CD3 T-cell engager | Drug | Control arm |
| InotuzumabAlso: BESPONSA, Inotuzumab ozogamicinCD22-directed antibody-drug conjugate | Drug | Control arm |
Primary outcome
Overall Survival (OS)
Time frame: 4 years
Time from randomization to death for any reason
15 secondary outcomes
Event Free Survival (EFS)
Time frame: 4 years
Percentage of patients who achieved MRD negative CR/CRi
Time frame: 4 years
Overall response rate
Time frame: 4 years
Duration of response (DOR)
Time frame: 4 years
Probability of patients who achieved CR/CRi at month 12
Time frame: 4 years
Prevalence of immunogenecity
Time frame: 4 years
Incidence of immunogenecity
Time frame: 4 years
Impact of immunogenicity on clinical response
Time frame: 4 years
Cellular kinetic profile by qPCR
Time frame: 4 years
Cellular kinetics profile by flow cytometry
Time frame: 4 years
Relationship between dose and response
Time frame: 4 years
Relationship between exposure and response
Time frame: 4 years
Relationship between dose and cellular kinetic
Time frame: 4 years
EQ-5D-3L
Time frame: 4 years
EORTC QLQ-30
Time frame: 4 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2020.
- Individual participant dataSharing planned: Undecided. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tisagenlecleucel, Blinatumomab and Inotuzumab in people with Acute Lymphoblastic Leukemia, run by Novartis Pharmaceuticals.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 9 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2020.