Phase 2
Completed N=34
Phase II Open Label Trial to Determine Safety & Efficacy of Tisagenlecleucel in Pediatric Non-Hodgkin Lymphoma Patients
Source: ClinicalTrials.gov NCT03610724 ↗Enrolled (actual)
34
Serious AEs
72.7%
Results posted
Mar 2024
Primary outcomePrimary: Overall Response Rate (ORR) as Determined by Local Investigator — 32.1 Percentage of participants
Summary
The purpose of the study was to assess the efficacy and safety of tisagenlecleucel in pediatric, adolescent and young adult patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) including Burkitt Lymphoma and Burkitt Leukemia.
For pediatric patients who have r/r B-NHL including Burkitt Lymphoma and Burkitt Leukemia, survival rates are dismal, only ~20-50% subjects are alive at 2 years with overall response rate (ORR) of 20-30% after conventional salvage chemotherapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Response Rate (ORR) as Determined by Local Investigator |
32.1 | — |
| SECONDARY Duration of Response (DOR) |
NA | — |
| SECONDARY Event Free Survival (EFS) |
2.1 | — |
| SECONDARY Relapse Free Survival (RFS) |
NA | — |
| SECONDARY Progression Free Survival (PFS) |
2.5 | — |
| SECONDARY Overall Survival (OS) |
10.4 | — |
| SECONDARY Cellular Kinetics Parameter: Cmax |
5140 | — |
| SECONDARY Cellular Kinetics Parameter: Tmax |
12.7 | — |
| SECONDARY Cellular Kinetics Parameter: AUC0-28d |
53500 | — |
| SECONDARY Cellular Kinetics Parameter: Clast |
344 | — |
| SECONDARY Cellular Kinetics Parameter: Tlast |
40.0 | — |
| SECONDARY Levels of Pre-existing and Treatment Induced Humoral Immunogenicity and Cellular Immunogenicity Against Tisagenlecleucel Cellular Kinetics, Safety and Efficacy |
87.9; 97.0 | — |
| SECONDARY Percentage of Participants Who Proceeded to Stem Cell Transplant (SCT) After Tisagenlecleucel Infusion |
21.2 | — |
| SECONDARY Maximum Positive Predictive Value (PPV) |
36.0 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed pediatric mature B-cell non-Hodgkin lymphoma (B-cell NHL) including the following subtypes; Burkitt lymphoma/ Burkitt leukemia (BL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), gray zone lymphoma (GZL), and follicular lymphoma (FL) Note: Patients with B-cell NHL associated with Nijmegen breakage syndrome will be allowed.
- Patients 25% by local assessment of bone marrow aspirate and/or biopsy.
- Karnofsky (age ≥16 years) or Lansky (age 2 weeks prior to laboratory assessment is allowed) defined as:
- Absolute neutrophil count (ANC) >1000/mm3
- Platelets ≥50000//mm3
- Hemoglobin ≥8.0 g/dl
- Adequate organ function defined as:
- a serum creatinine (sCR) based on gender/age as follows: Maximum Serum Creatinine (mg/dL) Age Male Female
1 to 91% on room air ii. No or mild dyspnea (≤Grade 1)
- Must have a leukapheresis material of non-mobilized cells accepted for manufacturing.
Exclusion Criteria
- Prior gene therapy or engineered T cell therapy.
- Prior treatment with any anti-CD19 therapy.
- Allogeneic hematopoietic stem cell transplant (HSCT) <3 months prior to screening and ≤4 months prior to infusion.
- Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD) in patients who received prior allogeneic HSCT.
- Prior diagnosis of malignancy other than study indication, and not disease free for 5 years.
- Clinically significant active infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, etc.)
- Presence of active hepatitis B or C as indicated by serology.
- Human Immunodeficiency Virus (HIV) positive test.
- Active neurological autoimmune or inflammatory disorders not related to B cell NHL (eg: Guillain-Barre syndrome, Amyotrophic Lateral Sclerosis)
- Active central nervous system (CNS) involvement by malignancy.
- Patients with B-cell NHL in the context of post-transplant lymphoproliferative disorders (PTLD) associated lymphomas.
Data sourced from ClinicalTrials.gov (NCT03610724). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.