Second Infusion of Tisagenlecleucel for Acute Lymphoblastic Leukemia

Not currently recruiting at 5 trial locations

Overseen By Kavitha Ramaswamy

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Non-standard chemotherapy

Disqualifiers: Infection, Pregnancy, Severe toxicities, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called tisagenlecleucel (also known as Kymriah, CTL019, CART-19, or tisa-cel) to determine if a second dose can help individuals with acute lymphoblastic leukemia (a type of blood cancer) remain in remission. Researchers aim to find out if an early second infusion can effectively keep cancer cells at bay and ensure the treatment's safety. This trial targets patients under 26 who have already received one dose of tisagenlecleucel, are in complete remission, but require additional help to prevent cancer recurrence. Participants must have tisagenlecleucel available for a second dose and must not have experienced severe side effects from the first treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that tisagenlecleucel is generally well-tolerated by patients with acute lymphoblastic leukemia. Earlier studies reported common side effects such as fever, tiredness, and low blood pressure, which are typical and manageable with medical care. Serious side effects, like cytokine release syndrome and some neurological issues, were also noted, but doctors are trained to treat these effectively.

Safety data from other studies indicate that while risks exist, most patients manage the side effects well. This treatment has also been used for other conditions, providing further evidence of its safety. Overall, the treatment is promising, but awareness of possible side effects is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tisagenlecleucel is unique because it harnesses the power of a patient's own immune system to fight acute lymphoblastic leukemia (ALL). Unlike traditional chemotherapy and radiation, Tisagenlecleucel is an autologous cellular immunotherapy, meaning it uses the patient's own T cells, which are modified and expanded outside the body to better target cancer cells. Researchers are excited about this treatment because it represents a more personalized approach, offering hope for patients who might not respond to existing therapies by potentially providing a more targeted and effective attack on cancer cells.

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

Research has shown that tisagenlecleucel, a type of CAR-T cell therapy, yields promising results for treating relapsed or hard-to-treat acute lymphoblastic leukemia (ALL). In previous studies, about 80% of patients achieved minimal residual disease-negative remission, meaning no cancer was detected three months after treatment. This suggests that the treatment can effectively eliminate cancer cells in many patients. Additionally, real-world studies have found that many patients remained cancer-free before needing further treatments, such as stem cell transplants. These findings support the potential effectiveness of tisagenlecleucel in treating ALL. Participants in this trial will receive a second infusion of tisagenlecleucel if they meet the eligibility criteria, further exploring its effectiveness in this context. ^{6 7 8 9 10}

Who Is on the Research Team?

Kevin Curran

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for children and young adults under 26 with B-cell Acute Lymphoblastic Leukemia who've had a previous tisagenlecleucel infusion. They must have normal organ function, no severe ongoing side effects from the first treatment, and not be pregnant or breastfeeding. Participants need to agree to use contraception if applicable.

Inclusion Criteria

Peripheral blood B-cell aplasia within 14 days prior to reinfusion

My recent tests show no cancer signs in my bone marrow.

My CAR T cell therapy is considered out of specification but is not expected to affect its safety or effectiveness.

Exclusion Criteria

I am a sexually active male unwilling to use a condom.

It has been over 60 days since my first tisagenlecleucel infusion.

Pregnant or lactating women or women of child-bearing potential not using highly effective contraception

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine prior to the initial tisagenlecleucel infusion

2-14 days

Initial Tisagenlecleucel Infusion

Participants receive the initial infusion of tisagenlecleucel

1 day

Early Reinfusion of Tisagenlecleucel

Participants receive a second infusion of tisagenlecleucel on day +30-60 after their initial infusion if meeting eligibility criteria

30-60 days post-initial infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the assessment of B-Cell Aplasia and toxicities

6 months

Long-term Follow-up

Participants are monitored for long-term safety and effectiveness, including the evaluation of toxicities

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Tisagenlecleucel

Trial Overview The study tests whether an early second dose of tisagenlecleucel can maintain cancer remission at six months post-first infusion in patients with B-ALL. It also evaluates the safety and effectiveness of this reinfusion strategy.

How Is the Trial Designed?

Group I: Tisagenlecleucel Experimental Treatment 1 Intervention

Patients will receive reinfusion of tisagenlecleucel on day +30-60 after their initial infusion if meeting eligibility criteria. Tisagenlecleucel is an autologous cellular immunotherapy product that is comprised of CD3+T cells that have undergone ex vivo T cell activation, gene modification, expansion, and formulation in infusible cryomedia.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Novartis Pharmaceuticals

Industry 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

Published Research Related to This Trial

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]

In a study of 31 pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel, 83.3% achieved a complete response, but 48% experienced disease relapse, indicating a significant challenge in long-term management.

High pretreatment leukemic burden (≥5% bone marrow blasts) was identified as a critical risk factor for poorer event-free survival (EFS) and overall survival (OS), suggesting that reducing this burden before CAR T-cell therapy could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of High Disease Burden on Survival in Pediatric Patients with B-ALL Treated with Tisagenlecleucel. Ravich, JW., Huang, S., Zhou, Y., et al.[2023]

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]

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]

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, a genetically modified T cell therapy, showed a high overall remission rate of 66.7% in a small group of Japanese patients with relapsed/refractory B-cell acute lymphoblastic leukemia, with some patients achieving long-lasting complete remission.

The treatment was associated with manageable side effects, including cytokine release syndrome in 83% of patients, which resolved with appropriate care, indicating a favorable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tisagenlecleucel in Japanese pediatric and young adult patients with relapsed/refractory B cell acute lymphoblastic leukemia. Hiramatsu, H., Adachi, S., Umeda, K., et al.[2022]

In a study of 32 patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) treated with tisagenlecleucel (tisa-cel), the level of CAR-T cell expansion in the body after treatment was found to be a key predictor of therapy success, rather than the specific characteristics of the CAR-T cells themselves.

Patients who had a higher percentage of certain T cell types (CD8+CD45RA+CD27+) before treatment were more likely to respond positively to the therapy, while those with primary refractory aggressive B-cell lymphomas showed poor outcomes, indicating that tumor biology plays a significant role in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the input material quality for the production of tisagenlecleucel by multiparameter flow cytometry and its relation to the clinical outcome. Štach, M., Pytlík, R., Šmilauerová, K., et al.[2023]

A post-marketing evaluation of tisagenlecleucel in pediatric patients revealed that 92% of the 638 reported adverse events were serious, often leading to hospitalization, with 55 cases resulting in fatal outcomes primarily due to leukemia progression or recurrence.

Cytokine release syndrome was the most common adverse event following tisagenlecleucel infusion, highlighting the need for ongoing monitoring of safety, especially since this analysis confirms the previously established safety profile but emphasizes the necessity for longer-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Children and Young Adults: Reverse Translational Research by Using Real-World Safety Data. Rafaniello, C., Ferrajolo, C., Gaio, M., et al.[2020]

In a study of 91 patients with relapsed/refractory large B-cell lymphoma (LBCL), treatment with the CAR T-cell therapy tisagenlecleucel (tisa-cel) resulted in a best overall response rate of 60% and a complete response rate of 32%, indicating its efficacy in a real-world setting.

The safety profile of tisa-cel was manageable, with only 5% of patients experiencing severe cytokine release syndrome and 1% experiencing neurotoxicity, suggesting that it can be safely administered in standard-of-care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. Iacoboni, G., Villacampa, G., Martinez-Cibrian, N., et al.[2021]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6237143/

CTL019 (tisagenlecleucel): CAR-T therapy for relapsed and ... CTL019 or tisagenlecleucel, the first CAR-T approved by the US Food and Drug Administration, showed impressive results in refractory/relapsed ALL.

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. 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.

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

Pooled safety analysis of tisagenlecleucel in children and ... Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia. John E Levine. John E Levine.

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 ...

10. fda.gov fda.gov/media/107296/download

KYMRIAH - Package Insert and Medication Guide The safety data described in the WARNINGS AND PRECAUTIONS and in this section reflect exposure to KYMRIAH in three non-randomized, single-arm studies in which ...