Tisagenlecleucel for Acute Lymphoblastic Leukemia

(CASSIOPEIA Trial)

Not currently recruiting at 95 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Tyrosine kinase inhibitors, Anti-CD19 therapy

Disqualifiers: Philadelphia chromosome, Hypodiploid, Burkitt's, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 29

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the efficacy and safety of a treatment called tisagenlecleucel for individuals with Acute Lymphoblastic Leukemia (ALL). The focus is on children and young adults who have undergone some treatment but still exhibit minimal residual disease (MRD). The trial administers a single dose of tisagenlecleucel, a therapy using modified immune cells designed to combat cancer. Participants must have been diagnosed with B-cell ALL, a type of leukemia affecting white blood cells, and still have active disease after first-line treatments. This trial may suit those who have completed initial treatments for B-cell ALL but have not fully responded. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that prior induction and consolidation chemotherapy is allowed, which suggests some treatments may be continued. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that tisagenlecleucel is likely to be safe for humans?

Previous studies have shown that tisagenlecleucel can cause some side effects, but many patients have tolerated it well. Research indicates that common side effects include fever, tiredness, and low blood pressure. Some patients have experienced more serious issues like cytokine release syndrome, a strong immune reaction, but these cases are often managed with supportive care. Importantly, the FDA has already approved tisagenlecleucel for treating certain types of leukemia, indicating a level of safety for its use in humans. Overall, the treatment's safety is well-documented, and healthcare providers closely monitor patients to manage any side effects effectively. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tisagenlecleucel is unique because it is a CAR-T cell therapy specifically designed to target and destroy cancer cells in Acute Lymphoblastic Leukemia (ALL). Unlike traditional treatments like chemotherapy, which can affect both healthy and cancerous cells, Tisagenlecleucel uses genetically engineered T cells to specifically recognize and attack leukemia cells. This targeted approach not only has the potential to be more effective but also reduces the risk of damaging healthy cells, leading to fewer side effects. Researchers are excited because this innovative mechanism could provide a powerful, personalized treatment option for patients with ALL.

What evidence suggests that tisagenlecleucel might be an effective treatment for acute lymphoblastic leukemia?

In this trial, participants will receive a single dose of tisagenlecleucel, also known as CTL019, to treat acute lymphoblastic leukemia (ALL). Previous studies have shown promising results, with about 80% of patients showing no signs of cancer three months after treatment, indicating the therapy's effectiveness. Specifically, one study found that a single dose of tisagenlecleucel led to long-lasting remission in patients whose B-cell ALL had returned or did not respond to other treatments. This evidence suggests that tisagenlecleucel can be effective for patients who have not responded well to other therapies. ^{4 6 7 8 9}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for young people (1-25 years old) with high-risk B-cell Acute Lymphoblastic Leukemia who've had first-line treatment but still have detectable cancer cells. They need to be generally healthy, with good heart, kidney, liver function and no severe breathing problems.

Inclusion Criteria

My leukemia is CD19 positive.

oxygen saturation of > 90% on room air

My ALT levels are within 5 times the normal limit for my age.

Exclusion Criteria

My cancer cells have fewer than 44 chromosomes or a low DNA index.

My bone marrow is still highly affected by cancer after initial treatment.

I have been diagnosed with Burkitt's lymphoma/leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Preparation phase before receiving tisagenlecleucel infusion

2-4 weeks

Treatment & Follow-up

Participants receive tisagenlecleucel infusion and are monitored frequently in the first month, then at Day 29, every 3 months for the first year, every 6 months for the second year, and yearly thereafter

8 years

Frequent visits in the first month, then at Day 29, every 3 months for the first year, every 6 months for the second year, then yearly

Survival

Monitoring of overall survival and disease-free survival

4-5 years

Post-study Long-term Follow-up

Long-term safety follow-up under a separate protocol per health authority guidelines

8 years

What Are the Treatments Tested in This Trial?

Interventions

• Tisagenlecleucel

Trial Overview The study tests the safety and effectiveness of a therapy called tisagenlecleucel (CTL019) in patients after initial leukemia treatments. It's an open-label phase II trial where participants are closely monitored over several phases including screening, pre-treatment, treatment & follow-up.

How Is the Trial Designed?

Group I: Single dose of CTL019 Experimental Treatment 1 Intervention

Based on the subject's weight one of two possible dose ranges will be prepared for the subject: Subjects ≤ 50 kg: 0.2 to 5.0 x 10(6) CAR-positive viable T cells per kg body weight OR Subjects \> 50 kg: 0.1 to 2.5 x 10(8) CAR-positive viable T cells

Tisagenlecleucel is already approved in United States, European Union for the following indications:

Approved in United States as Kymriah for:

• B-cell acute lymphoblastic leukemia (ALL) in patients up to 25 years old
• Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in European Union as Kymriah for:

• B-cell acute lymphoblastic leukemia (ALL) in patients up to 25 years old
• Relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Published Research Related to This Trial

The total estimated cost for treating pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia using tisagenlecleucel is $612,779, which includes significant additional costs beyond the drug's list price of $475,000.

Adverse event management and inpatient admissions were the main contributors to the additional costs, highlighting the importance of considering these factors in the overall economic evaluation of tisagenlecleucel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimation of Total Costs in Pediatric and Young Adult Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia Receiving Tisagenlecleucel from a U.S. Hospital's Perspective. Yang, H., Hao, Y., Qi, CZ., et al.[2023]

Tisagenlecleucel, a CAR-T cell therapy, shows high overall remission rates of 69% to 93% in patients with relapsed/refractory B-cell acute lymphoblastic leukemia, with durable 12-month relapse-free survival rates of 55% to 59%.

However, the treatment is associated with significant risks, including potentially life-threatening cytokine release syndrome in 77% to 100% of patients and neurotoxicity in 31% to 45%, highlighting the need for careful patient selection and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Acute Lymphoblastic Leukemia: A Review of the Literature and Practical Considerations. Halford, Z., Anderson, MK., Bennett, LL., et al.[2021]

In a study of 14 infants with B-cell acute lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel, 64% achieved minimal residual disease-negative remission, indicating significant efficacy of this CAR T-cell therapy in a population previously excluded from clinical trials.

The therapy was generally well-tolerated, with only 3 patients experiencing severe cytokine release syndrome and no reports of neurotoxicity, suggesting that tisagenlecleucel is a safe treatment option for infants with this aggressive form of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world use of tisagenlecleucel in infant acute lymphoblastic leukemia. Moskop, A., Pommert, L., Baggott, C., et al.[2022]

Tisagenlecleucel, a CAR T-cell therapy for relapsed/refractory B-ALL, showed an 85% complete response rate in infused patients and a 12-month overall survival rate of 72%, indicating its efficacy in treating this condition.

Patients with a high disease burden before treatment had significantly worse outcomes and higher rates of severe side effects, highlighting the importance of disease status in predicting treatment success and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease Burden Affects Outcomes in Pediatric and Young Adult B-Cell Lymphoblastic Leukemia After Commercial Tisagenlecleucel: A Pediatric Real-World Chimeric Antigen Receptor Consortium Report. Schultz, LM., Baggott, C., Prabhu, S., et al.[2023]

Tisagenlecleucel (Kymriah) is an effective treatment for B-cell precursor acute lymphoblastic leukemia (ALL) in patients up to 25 years old, achieving a complete remission rate of 63% in a study of 63 participants, with all remissions showing minimal residual disease (MRD) below 0.01%.

While the treatment shows promise, it is associated with serious side effects, including cytokine release syndrome (79%) and neurologic events (65%), but the overall benefit-risk profile is considered acceptable for patients with resistant forms of ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia. O'Leary, MC., Lu, X., Huang, Y., et al.[2020]

In a study of 79 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia, those who responded to the CAR T-cell therapy tisagenlecleucel showed approximately double the expansion of the therapy in their blood compared to nonresponders, indicating a strong correlation between cellular expansion and treatment efficacy.

The therapy demonstrated persistence in responders for over two years, and its expansion continued even after treatment with tocilizumab, which is used to manage cytokine release syndrome, suggesting that tisagenlecleucel can remain effective despite potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia. Mueller, KT., Waldron, E., Grupp, SA., et al.[2020]

Tisagenlecleucel, a CAR T cell therapy for relapsed/refractory B cell acute lymphoblastic leukemia, showed a high incidence of grade 3/4 adverse events (77% of patients), including cytokine-release syndrome (79%) and prolonged cytopenias (40%).

Despite the significant adverse events, the therapy led to complete remission in patients, with effective management of complications such as CRS using tocilizumab and corticosteroids, and a low incidence of severe infections after one year due to immunoglobulin replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia. Levine, JE., Grupp, SA., Pulsipher, MA., et al.[2022]

Tisagenlecleucel (tisa-cel) is an effective CAR-T therapy for patients with relapsed/refractory follicular lymphoma (R/R FL), showing durable remissions even in high-risk patients, as confirmed by the pivotal ELARA study.

The therapy has a manageable toxicity profile, making it a viable option for patients who have undergone two lines of systemic therapies, leading to its FDA approval for this indication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel: CAR-T cell therapy for adult patients with relapsed or refractory follicular lymphoma. Saha, A., Jhaveri, K., Sarfraz, H., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10294746/

Kymriah® (tisagenlecleucel) – An overview of the clinical ... This article presents a high-level overview of the clinical development journey of tisagenlecleucel, including its efficacy outcomes and safety considerations.

2. kymriah-hcp.com kymriah-hcp.com/acute-lymphoblastic-leukemia-children/efficacy

KYMRIAH® (tisagenlecleucel) Efficacy Data & Clinical Trials About 8/10 patients achieved minimal residual disease negative (MRD-negative) remission at 3 months after treatment with KYMRIAH (tisagenlecleucel).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07039383

NCT07039383 | A Real-world Study of the Effectiveness ... This was a retrospective, cross-sectional, center-based chart review study that collected real-world data for relapsed/refractory (R/R) ...

4. astctjournal.org astctjournal.org/article/S2666-6367(25)00363-X/fulltext

Kymriah Real-World Effectiveness and Functional ... 65% of pts who went on to alloSCT (22/34) were in B-cell recovery at time of transplant; 71% of pts (24/34) were relapse-free prior to alloSCT. Safety and ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1709866

Tisagenlecleucel in Children and Young Adults with B-Cell ... A single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B ...

6. kymriah-hcp.com kymriah-hcp.com/acute-lymphoblastic-leukemia-children/safety-profile

Adverse Events & Safety | KYMRIAH® (tisagenlecleucel) | HCP Updated analysis of the efficacy and safety of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8344270/

Pooled safety analysis of tisagenlecleucel in children and ... The trials had similar designs, eligibility criteria, and dosing, permitting pooling of data for characterization of tisagenlecleucel safety.

8. us.kymriah.com us.kymriah.com/

KYMRIAH® (tisagenlecleucel) | Official Patient Website Find info about KYMRIAH® (tisagenlecleucel) Suspension for IV infusion, the conditions it treats, and Important Safety Info, including Boxed Warning.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02228096

Study of Efficacy and Safety of CTL019 in Pediatric ALL ... Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia. J Immunother Cancer. 2021 Aug;9(8):e002287 ...