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AzTrials

B-cell Acute Lymphoblastic LeukemiaPhase 2NCT04156659

Study of Tisagenlecleucel in Chinese Pediatric and Young Adult Subjects With Relapsed or Refractory B-cell ALL

A Phase 2 study testing Tisagenlecleucel in people with B-cell Acute Lymphoblastic Leukemia, run by Novartis Pharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a single arm, multi-center, phase II study to evaluate the efficacy and safety of tisagenlecleucel in Chinese pediatric and young adult subjects with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) Read more about this study

Who is it for?
Ages Up to 25 years
Conditions the study is for
B-cell Acute Lymphoblastic Leukemia
What is being tested?
Tisagenlecleucel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
30 Nov 2021to 30 Nov 2027
Phase
Phase 2
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 Up to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Chinese patients age ≤25 years at the time of informed consent form (ICF) signature.
  • Relapsed or refractory B-cell ALL
  • 2nd or greater bone marrow (BM) relapse OR
  • Any BM relapse after allogeneic SCT and must be ≥ 3 months from SCT at the time of screening OR
  • Primary refractory as defined as not achieving a CR after 2 cycles of a standard first line chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia OR
  • Subjects with Ph+ ALL are eligible if they are intolerant to or relapsed/refractory after two lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated OR
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  • Ineligible for allogeneic SCT because of: comorbid disease; other contraindications to allogeneic SCT conditioning regimen; lack of suitable donor; prior SCT; subject declines allogeneic SCT as a therapeutic option after documented discussion about the role of SCT with a BMT physician not part of the study team
  • For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of screening
  • Bone marrow with ≥ 5% lymphoblasts on local morphologic assessment at screening
  • Adequate performance status, cardiac, hepatic, renal and pulmonary function at screening
  • Must meet the institutional criteria to undergo leukapheresis
  • Once all other eligibility criteria are confirmed, must have a leukapheresis material of non-mobilized cells received and accepted for manufacturing.

Who cannot join

  • Isolated extra-medullary disease relapse
  • Subjects with concomitant genetic syndromes associated with bone marrow failure states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Subjects with Down syndrome will not be excluded.
  • Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
  • Prior anti-CD19 directed therapy, gene therapy or adoptive T cell therapy
  • CNS involvement by ALL, defined as CNS-2 and CNS-3 disease per National Comprehensive Cancer Network guidelines NCCN 2018 v1
  • Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre syndrome)
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  • History or presence of clinically relevant CNS pathology, e.g., epilepsy, paresis, aphasia, stroke, severe brain injuries, cerebellar disease, organic brain syndrome, or psychosis.
  • Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to screening NOTE: Investigational therapies must not be used at any time while on study until the first progression following tisagenlecleucel infusion.
  • Previous or concurrent malignancy except for curatively treated non-melanoma skin cancers, in situ carcinoma (e.g. cervix, skin), and cancers in complete remission for at least 3 years and without evidence of recurrence

About this study

Official title: A Phase II, Single Arm, Multi-center Trial to Evaluate the Efficacy and Safety of Tisagenlecleucel in Chinese Pediatric and Young Adult Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

This is a single arm, multi-center, phase II study to evaluate the efficacy and safety of tisagenlecleucel in Chinese pediatric and young adult subjects with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL)

Read the detailed description

The study will have the following sequential phases for all subjects:

  • Screening
  • Pre-Treatment (Cell Product Preparation and Lymphodepleting Chemotherapy)
  • Treatment and Follow-up Tisagenlecleucel infusion should occur within 16 weeks of informed consent. The total duration of the study is 5 years. After tisagenlecluecel infusion, efficacy will be assessed monthly for the first 6 months, then quarterly up to 2 years and semi-annually afterwards up to 5 years, or until the subject relapses.
Being tested
Tisagenlecleucel
Keywords
Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia, ALL, Tisagenlecleucel, CTL019, China
Medical subject headings
Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TisagenlecleucelBiological

    Also called CTL019

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

Study groups in NCT04156659
Study groupRoleWhat they receive
TisagenlecleucelExperimentalAll patients eligible for treatment with tisagenlecleucel will receive a single dose of tisagenlecleucel. For subjects ≤ 50 kg, tisagenlecleucel will be administered as a single infusion of 0.2 to 5.0 x 10^6 CAR positive viable T cells per kg body weight. For subjects > 50 kg, tisagenlecleucel will be administered as a single infusion of 0.1 to 2.5 x 10^8 CAR positive viable T cells.
Receives: Biological: Tisagenlecleucel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Remission Rate (ORR)

    Evaluate the efficacy of tisagenlecleucel using overall remission rate (ORR) during the 3 months after tisagenlecleucel administration as assessed by the investigator. The ORR is defined as the proportion of subjects with a best overall disease response of Complete Remission (CR) or Complete Remission with Incomplete blood count recovery (CRi)

    Measured: From first dosing (single administration, Day 1) up to Month 3

Secondary outcomes (13)

  1. CR or CRi rate at month 6

    Evaluate the percentage of participants who achieve CR or CRi at Month 6 without SCT after tisagenlecleucel infusion

    Measured: Month 6

  2. CR or CRi rate at Day 28

    Evaluate the percentage of participants who achieve CR or CRi at Day 28 after tisagenlecleucel infusion

    Measured: Day 28

  3. Best Overall Response (BOR) of CR or CRi with a MRD negative bone marrow

    Evaluate the percentage of participants who achieve a BOR of CR or CRi with a MRD negative bone marrow during the 3 months after tisagenlecleucel infusion

    Measured: From first dosing (single administration, Day 1) up to Month 3

  4. Duration of remission (DOR)

    DOR, i.e. the time from achievement of CR or CRi, whichever occurs first, to relapse or death due to ALL

    Measured: Average of 60 Months

  5. Relapse free survival (RFS)

    RFS, i.e. the time from achievement of CR or CRi whichever occurs first to relapse or death due to any cause during CR or CRi

    Measured: Avarage of 60 Months

  6. Event free survival (EFS)

    EFS, i.e. the time from date of Tisagenlecleucel infusion to the earliest of death, relapse or treatment failure

    Measured: Average of 60 Months

  7. Overall survival (OS)

    OS, i.e. the time from date of tisagenlecleucel infusion to the date of death due to any reason

    Measured: Average of 60 Months

  8. Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths

    Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) parameters.

    Measured: From Screening up to Month 60

  9. In vivo cellular PK profile of tisagenlecleucel

    qPCR and flow cytometry will be used to measure tisagenlecleucel transgene concentration in blood, bone marrow and other matrices/tissues

    Measured: Up to Month 60

  10. Serum cytokine

    Concentrations of soluble factors (such as IL-10, iFN-y, IL-6) in blood will be summarized by participant and time point

    Measured: Up to Month 60

  11. Levels of pre-existing and treatment induced humoral immunogenicity

    The humoral immunogenicity assay measures the antibody titers specific to tisagenlecleucel prior to and following infusion

    Measured: Up to Month 60

  12. Tociluzumab PK

    Concentrations of tocilizumab

    Measured: Up to Day 7 after tocilizumab infusion

  13. Levels of prexisting and treatment induced cellular immunogenicity

    The cellular immunogenicity assay will assess the presence of T lymphocyte activated by the tisagenlecleucel protein

    Measured: Up to Month 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2019
  2. Study start30 Nov 2021 (estimated)
  3. Primary completion30 Nov 2022 (estimated)
  4. Study completion30 Nov 2027 (estimated)

Why it stopped: This study was cancelled before enrolling any patients for business related reasons.

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04156659
Sponsor's protocol ID
CCTL019B2210
Status last verified
Mar 2023
First submitted
23 Oct 2019
Last updated
9 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tisagenlecleucel in people with B-cell 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 12 inclusion and 9 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 Mar 2023. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Remission Rate (ORR) (time frame: From first dosing (single administration, Day 1) up to Month 3). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04156659.

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 Mar 2023.

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