Acute Lymphoblastic Leukemia
Conditions
Keywords
Acute lymphoblastic leukemia, tisagenlecleucel, intouzumab, blinatumomab, CAR-T, CTL019
Brief summary
This trial aims to compare the benefits and risks of tisagenlecleucel to blinatumomab or inotuzumab in adult patients with relapsed or refractory ALL. This trial investigates tisagenlecleucel as an additional treatment option for this patient population with high unmet medical need.
Interventions
BIOLOGICALTisagenlecleucel
autologous cellular immunotherapy product
DRUGBlinatumomab
bispecific CD19-directed CD3 T-cell engager
DRUGInotuzumab
CD22-directed antibody-drug conjugate
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a phase III, open label, multinational, randomized trial. Eligible patients will be randomized 1:1 to Tisagenlecleucel treatment strategy (tisagenlecleucel after optional bridging chemotherapy and lymphodepleting chemotherapy) or control arm treatment strategy (blinatumomab or inotuzumab per investigator's discretion after optional bridging chemotherapy). The randomization will be performed stratifying for the number of prior salvage therapies (0 vs. 1) and prior allogenic stem cell transplant (yes vs. no).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent. 2. Age ≥ 18 years. 3. Subject with CD19-expressing B-ALL. 4. Adequate organ function. 5. Patients considered in any of the following settings are eligible: 1. Untreated first or second relapse 2. Refractory to primary induction therapy 3. Refractory to first salvage therapy or 4. Relapse after allogenic stem cell transplant.
Exclusion criteria
1. Patients presenting with untreated first relapse of ALL more than 24 months after initial diagnosis 2. Presence of extra-medullary disease. 3. History or presence of clinically relevant CNS pathology, or uncontrolled CNS leukemia. 4. History of Veno-occlusive Disease (VOD). 5. Active neurological autoimmune or inflammatory disorders. 6. Active acute Graft-versus-Host Disease (GvHD), grade 2-4. Other protocol-defined Inclusion/Exclusion may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 4 years | Time from randomization to death for any reason |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients who achieved MRD negative CR/CRi | 4 years | Percentage of patients who achieved MRD negative CR/CRi at month 3 post randomization |
| Overall response rate | 4 years | ORR is defined as the proportion of subjects with best overall response (BOR) of CR or CRi, where the BOR is defined as the best response recorded from randomization until the start of new anticancer therapy or the data cut-off date, whichever is earlier |
| Duration of response (DOR) | 4 years | DOR is defined as the duration from the date when the response criteria of CR/CRi is first met to the date of relapse or death due to underlying cancer. |
| Probability of patients who achieved CR/CRi at month 12 | 4 years | Probability of achieving CR/CRi based on all response assessments between randomization and month 12. This outcome measure will be based on all randomized patients and the assessment will be up to 48 months (from randomization of the first patient until 12 months after the randomization of the last patient). |
| Prevalence of immunogenecity | 4 years | Percentage of patients who have anti-tisagenlecleucel antibodies in the serum before randomization |
| Incidence of immunogenecity | 4 years | Percentage of patients who develop anti-tisagenlecleucel antibodies in the serum after infusion of tisagenlecleucel |
| Impact of immunogenicity on clinical response | 4 years | difference in response between patients with immunogenicity and patients without immunogenicity |
| Event Free Survival (EFS) | 4 years | EFS, assessed up to 48 months, is defined as the date from randomization to the earliest of (a) date of death due to any cause, (b) relapse after CR/CRi, or (c) treatment failure, which is defined as failure to achieve remission within 12 weeks of randomization. |
| Cellular kinetics profile by flow cytometry | 4 years | Summary of flow cytometry-detected tisagenlecleucel transgene concentrations |
| Relationship between dose and response | 4 years | Relationship between the administered dose of tisagenlecleucel and response to treatment (complete response with or without hematological recovery). This assessment will be done for all patients for up to 48 months. |
| Relationship between exposure and response | 4 years | Describe the relationship between the cellular kinetics of tisagenlecleucel overtime and response. |
| Relationship between dose and cellular kinetic | 4 years | Describe the relationship between the dose of tisagenlecleucel actually administered and cellular kinetics |
| EQ-5D-3L | 4 years | Patient reported outcome measure |
| EORTC QLQ-30 | 4 years | Patient reported outcome measure |
| Cellular kinetic profile by qPCR | 4 years | Summary of qPCR detected tisagenlecleucel transgene concentrations |
Outcome results
None listed