Acute Lymphoblastic Leukemia
Conditions
Keywords
CTL019, Kymriah, Tisagenlecleucel, B-Cell Acute Lymphoblastic Leukemia, Leukemia, ALL, Pediatric, Young Adult, Reinfusion
Brief summary
This was a multi-center Phase II study investigating the efficacy and safety of reinfusion of tisagenlecleucel in pediatric and young adult patients with acute lymphoblastic leukemia (ALL) who were treated with tisagenlecleucel and experience B cell recovery.
Detailed description
This trial was a phase II, open label, multi-center trial to determine the efficacy and safety of tisagenlecleucel re-infusion in pediatric and adolescent young adult (AYA) patients with acute lymphoblastic leukemia (ALL) experiencing loss of B cell aplasia. Loss of B-cell aplasia is defined as: peripheral blood (PB) absolute B lymphocyte count ≥ 50/µL, OR PB B lymphocyte ≥ 10% of the total lymphocytes. B-cell aplasia is defined as PB absolute B lymphocyte count \<50/µL. The study had the following phases for all patients: Screening, Treatment and Follow-up. The total duration of the study was about 12 months. After tisagenlecleucel re-infusion, efficacy was assessed at months 1, 3, 6, and End of Study at which time blood samples were obtained. The study stopped early due to slow enrollment into the trial. The rate of enrollment made the trial no longer feasible to continue. The patients were able to voluntarily withdraw from the study for any reason, at any time. Patients who received commercial tisagenlecleucel had to be followed for up to 15 years post-infusion. Patients could have been followed under the Center for International Blood and Marrow Transplant Research (CIBMTR) cellular therapy registry if consented for participation. For patients who do not provide consent for participation in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, adverse events were to be reported for 15 years or until the patient enrolls in the registry.
Interventions
BIOLOGICALTisagenlecleucel
Tisagenlecleucel Cell Dispersion for Infusion given once during the study. The approved dose range for tisagenlecleucel is: 0.2 to 5.0×106 CAR positive viable T cells / kg for patients' ≤ 50 kg body weight or 0.1 to 2.5×108 CAR-positive viable T cells for patients \> 50 kg body weight.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent must be obtained prior to participation in the study * Must have an additional dose of unexpired, commercial tisagenlecleucel available and prescribed by a physician in the course of medical practice * Age up to and including 25 years * Patients must have CD-19+ Leukemia * Patients who were previously treated with tisagenlecleucel and present with evidence of B-cell recovery as defined by: Peripheral blood (PB) absolute B lymphocyte count ≥ 50/µL, OR PB B lymphocyte ≥ 10% of the total lymphocytes
Exclusion criteria
* Prior gene therapy other than tisagenlecleucel * Prior adoptive T cell therapy other than tisagenlecleucel * Active CNS involvement by malignancy * Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection at screening * HIV positive test within 8 weeks of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Establish B Cell Aplasia Within 9 Months of Reinfusion | Post-reinfusion up to 9 months (Day 1 is excluded) | Percentage of patients who establish B-cell aplasia at any visit following re-infusion with tisagenlecleucel. B-cell aplasia is defined as peripheral blood (PB) absolute B lymphocyte count \<50/μL. Planned timeframe was 12 months but actual timeframe was approximately 9 months due to early termination of the trial. Day 1 is post lymphodepleting chemotherapy and pre-reinfusion of tisagenlecleucel. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Post-reinfusion up to 9 months | Overall remission rate (ORR) was defined as the percentage of participants with a best overall disease response of complete remission (CR) or CR with incomplete blood count recovery (CRi). However, the rate was not calculated due to low enrollment. Participants' best responses have been listed by day and participants may be counted more than once. |
| Participants With an Event | Reinfusion up to 9 months | An event was defined as one of the following: death from any cause after remission, relapse, treatment failure (defined as no response in the study or discontinuation from the study for death, adverse event, lack of efficacy or progressive disease or new cancer therapy). |
| Overall Survival (OS) | Reinfusion up to 9 months | Deaths due to any reason. |
Countries
United States
Participant flow
Pre-assignment details
There were 7 participants screened.
Participants by arm
| Arm | Count |
|---|---|
| Tisagenlecleucel Tisagenlecleucel Cell Dispersion for Infusion given once during the study.
The approved dose range for tisagenlecleucel is: 0.2 to 5.0×10\^6 CAR positive viable T cells / kg for patients' ≤ 50 kg body weight or 0.1 to 2.5×10\^8 CAR-positive viable T cells for patients \> 50 kg body weight. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Study terminated by sponsor | 3 |
Baseline characteristics
| Characteristic | Tisagenlecleucel |
|---|---|
| Age, Customized >=10 to <18 years | 2 Participants |
| Age, Customized < 10 years | 2 Participants |
| Age, Customized >=18 years | 1 Participants |
| Race/Ethnicity, Customized White | 5 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 4 / 5 |
| serious Total, serious adverse events | 3 / 5 |
Outcome results
Primary
Percentage of Patients Who Establish B Cell Aplasia Within 9 Months of Reinfusion
Percentage of patients who establish B-cell aplasia at any visit following re-infusion with tisagenlecleucel. B-cell aplasia is defined as peripheral blood (PB) absolute B lymphocyte count \<50/μL. Planned timeframe was 12 months but actual timeframe was approximately 9 months due to early termination of the trial. Day 1 is post lymphodepleting chemotherapy and pre-reinfusion of tisagenlecleucel.
Time frame: Post-reinfusion up to 9 months (Day 1 is excluded)
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tisagenlecleucel | Percentage of Patients Who Establish B Cell Aplasia Within 9 Months of Reinfusion | 2 Participants |
Secondary
Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day
Overall remission rate (ORR) was defined as the percentage of participants with a best overall disease response of complete remission (CR) or CR with incomplete blood count recovery (CRi). However, the rate was not calculated due to low enrollment. Participants' best responses have been listed by day and participants may be counted more than once.
Time frame: Post-reinfusion up to 9 months
Population: Full analysis set - Data was not adequate to perform overall remission rate analysis considering evaluable population size
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 34 | 1 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 24 | 0 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 28 | 1 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 29 | 1 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 32 | 1 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 67 | 1 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 84 | 0 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 91 | 0 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 177 | 0 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 182 | 1 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 211 | 0 responses |
| Tisagenlecleucel | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 274 | 0 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 211 | 1 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 84 | 1 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 24 | 1 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 182 | 0 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 28 | 0 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 91 | 1 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 29 | 0 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 274 | 1 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 32 | 0 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 34 | 0 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 177 | 1 responses |
| Complete Remission Without Complete Blood Count Recovery | Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day | Day 67 | 0 responses |
Secondary
Overall Survival (OS)
Deaths due to any reason.
Time frame: Reinfusion up to 9 months
Population: Full analysis set - Data was not adequate to perform overall survival analysis considering evaluable population size
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel | Overall Survival (OS) | 0 deaths |
Secondary
Participants With an Event
An event was defined as one of the following: death from any cause after remission, relapse, treatment failure (defined as no response in the study or discontinuation from the study for death, adverse event, lack of efficacy or progressive disease or new cancer therapy).
Time frame: Reinfusion up to 9 months
Population: Full analysis set - Data was not adequate to perform time to event analysis considering evaluable population size.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tisagenlecleucel | Participants With an Event | 1 participant |