Characterizing secondary T‑cell cancers after tisagenlecleucel

A Non-Interventional Study (NIS) PASS to Characterize Secondary Malignancies of Tcell Origin Following Tisagenlecleucel Therapy (CCTL019B2402)

This will test tumor or blood samples from people who developed a T‑cell secondary cancer after receiving tisagenlecleucel to see if the CAR transgene or replication‑competent virus might be involved.

Quick facts

• Study type: Observational
• Enrollment: 30 (estimated)
• Ages: 15 Years to 15 Years
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Locations: 3 sites (Kurume, Fukuoka and 2 other locations)
• Trial ID: NCT07378969 on ClinicalTrials.gov

What this trial studies

This is a non‑interventional post‑authorization safety surveillance program enrolling people who developed a confirmed secondary T‑cell malignancy after receiving tisagenlecleucel in either clinical trials (Cohort 1) or the commercial setting (Cohort 2). The study collects existing tumor tissue, bone marrow aspirates, blood, or extracted DNA and performs targeted testing for the muCAR19 transgene, replication‑competent lentivirus (RCL), and additional genomic analyses as warranted. Enrollment is open for up to about 15 years from the last approved indication and uses centralized laboratory testing and clinical review to interpret results. No investigational treatments are given; the work is observational sample testing to explore possible links between therapy and secondary T‑cell oncogenesis.

Who should consider this trial

Good fit: Ideal candidates are people who previously received tisagenlecleucel and now have a confirmed secondary T‑cell malignancy with existing tumor, bone marrow, or blood/DNA samples available for testing.

Not a fit: Patients without a confirmed T‑cell secondary malignancy or without accessible tissue/blood samples (or in regions where sharing redacted pathology is not permitted) are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this work could clarify whether tisagenlecleucel contributes to secondary T‑cell cancers, leading to better safety monitoring and clearer guidance for future patients.

How similar studies have performed: Pharmacovigilance and tissue‑testing efforts for CAR‑T products have previously identified rare cases and occasionally detected transgene sequences, but a dedicated PASS focused on secondary T‑cell malignancies after tisagenlecleucel is relatively novel.

Eligibility criteria

Inclusion Criteria:

Study participants eligible for inclusion in this study must meet all of the following criteria:

1. Prior use of tisagenlecleucel treatment in CTL019 clinical trial setting or post-marketing/commercial tisagenlecleucel setting as outlined for Cohort 1 and Cohort 2
2. Confirmed diagnosis of secondary malignancy of T-cell origin via redacted pathology report and/or clinical confirmation by the Principal Investigator/clinician responsible for enrolling the participant. Clinical judgement may be required in cases where the diagnosis is not clearly confirmed in the redacted pathology report. There also may be cases in certain site/countries, where sharing the redacted pathology reports is not allowed, hence the clinical diagnosis will be allowed for eligibility.
3. Availability of existing secondary malignancy of T cell origin specimen(s) from tissue, and/or bone marrow aspirate sample(s) and/or blood or DNA extracted from blood (with confirmed T-cell malignancy diagnosis in the sample provided) collected during routine standard of care during the secondary malignancy of T-cell origin diagnosis. Often, only a limited amount of the appropriate sample(s) may be available. For the testing process, a specimen containing the malignant T-cells for the secondary malignancy of T-cell origin must be present. The type of specimen/sample for testing is determined based on the location of the secondary malignancy of T-cell origin. For example, bone marrow aspirate and/or blood and/or bone marrow biopsy may be needed for analysis for a secondary malignancy of T cell origin when the malignant T cells are present in blood and/or bone marrow, and tissue such as a lymph node location or cutaneous or other location is needed when this is the region of the body affected by the secondary malignancy of T-cell origin. Blood, (even if NOT involved with the T cell malignant cells) when available, may also be used for comparison to the tissue/bone marrow used for the analysis. Novartis has established ranges of CAR transgene level in blood for all 3 pivotal trial indications at specific time points. This is used for comparison.

   See laboratory manual for detailed instructions. The following types of samples are recommended for collection if available/pre-existing:
   1. Tumor tissue (FFPE block (ambient temp), unstained slides (ambient temp), or bone marrow aspirate in EDTA or blood in EDTA and frozen, if malignant T-cells present)
   2. Peripheral blood EDTA frozen- to be used when available and either not involved with T-cell malignancy for comparison to the tumor sample provided and/or if peripheral blood has circulating malignant T cells for analysis.
   3. Bone marrow aspirate EDTA frozen if involved with secondary malignancy of T-cell origin.
   4. DNA extracted from blood or bone marrow aspirate stored frozen
   5. Bone marrow biopsy if malignant T-cells are present (FFPE block, unstained slides, ambient temperature)
4. Signed informed consent. For participants who have died, it is acceptable for clinical/academic sites to use a previous biospecimen research consent, or to have an appropriate family member or designated representative to provide consent on behalf of the participant as per local regulations.

Exclusion Criteria:

Study participants meeting any of the following criteria are not eligible for inclusion in this study:

1. Ongoing enrollment on Novartis sponsored CTL019 interventional or LTFU clinical trial
2. Cases where there is no existing available specimens that include the secondary malignancy of T cell origin (tumor tissue and/or existing blood and/or bone marrow and/or DNA from blood for testing)
3. Cases where informed consent is not possible.

Where this trial is running

Kurume, Fukuoka and 2 other locations

• Novartis Investigative Site — Kurume, Fukuoka, Japan (Recruiting)
• Novartis Investigative Site — Osaka, Osaka, Japan (Recruiting)
• Novartis Investigative Site — Bunkyo Ku, Tokyo, Japan (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Secondary Malignancies of T-cell Origin; NIS; PASS; secondary malignancies of T-cell origin; tisagenlecleucel