Refractory B-cell Acute Lymphoblastic Leukemia, Relapsed B-cell Acute Lymphoblastic Leukemia
Conditions
Brief summary
This is a phase II clinical study to evaluate the safety and efficacy of CAR-T-19 injection in the treatment of CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia.
Detailed description
This is a multiple-center, single-arm, open-label study. After meeting the eligibility criteria and enrolling on the trial, patients will undergo leukapheresis for collection of autologous lymphocytes, patients will then proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of CD19 CAR T-cells at a target dose of 2.5 x10\^6 cells/kg（range 0.8-2.5×10\^6 cells/kg）.
Interventions
BIOLOGICALCAR-T-19 cell injection
The functional component of CAR-T-19 cell injection is T cells that have been genetically modified to express anti CD19 chimeric antigen receptors.
Sponsors
Beijing Yongtai Ruike Biotechnology Company Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntary participation in clinical trial, The Participants or his legal guardian is fully understands this clinical trial and signs the Informed Consent Form (ICF); Willing to follow and be able to complete all trial procedures. 2. Age≤25 years old at the time of screening, regardless of gender. 3. Bone marrow examination confirmed the diagnosis of B-ALL, and meet one of the following conditions： Relapsed B-ALL：1）Relapse within 12 months of the first remission；2）Recurrence occurring again more than 12 months after the first remission,, relapsed or not responded after first-line/multi-line salvage chemotherapy；3) Experienced two or more bone marrow recurrences; 4） recurrence after autologous or allogeneic hematopoietic stem cell transplantation； Refractory B-ALL：1）failed to achieve complete remission after 2 cycles of standard induction chemotherapy. 4. Ph+ALL patients are eligible：1）Relapsed or refractory after receiving at least two Tyrosine kinase inhibitors (TKI) treatments；If Ph+ALL patients with t315i mutation are resistant to first- and second-generation TKIs, in the absence of effective TKI therapy, patients are not required to receive at least two TKIs；2）cannot tolerate TKI treatment；3）Presence of contraindications to TKI therapy. 5. Bone marrow (BM) or peripheral blood (PB) tumor cells were measured to express CD19 at screening. 6. Bone marrow blasts ≥ 5% at screening. 7. Adequate organ function and must meet the following criteria： Alanine aminotransferase (ALT) ≤ 5 ×Upper limit of normal value(ULN)；Total serum bilirubin ≤ 2.0 ×ULN(（for Gilbert syndrome, total bilirubin≤3.0×ULN)；in non-oxygen state, No \> grade 1 dyspnea, Blood oxygen saturation \> 95%；left ventricular ejection fraction(LVEF) ≥ 50%；Serum creatinine≤1.5 × ULN； 8. Karnofsky（age≥16 years）performance status≥70 or Lansky（age\<16 years）performance status≥50. 9. Life expectancy ≥ 12 weeks. 10. Adequate venous access (for apheresis) and no other contraindications to apheresis. 11. Negative blood/urine pregnancy test in women of childbearing potential before screening and within 3 days prior to cell infusion, and any male and female patients of childbearing potential must agree to use an effective method of contraception throughout the study and for at least 2 years after CAR-T-19 infusion. In the judgment of the investigator, a patient of childbearing potential means that he/she is biologically capable of having children and having a normal sexual life. 12. For Participants who have previously undergone allogeneic hematopoietic stem cell transplantation, CAR-T-19 cell preparation is performed using their previous donor peripheral blood， and the donor needs to meet the following conditions：1）Have donated bone marrow/hematopoietic stem cells as a transplant donor for the patient；2）Age ≥8 years at screening；3）Voluntary participation in clinical studies; the donor (and legal guardian, if applicable) am fully aware of and informed about this trial and have signed an informed consent form (ICF); Willing to follow and be able to complete all trial procedures；4）Have adequate venous access (for apheresis or venous blood collection) and no other contraindications to apheresis; 5) The etiological test results do not correspond to any of the
Exclusion criteria
outlined in item 12. 6) Women of childbearing age have negative blood and urine pregnancy tests.7) Systemic glucocorticoid therapy is prohibited within one week prior to apheresis, with the exception of physiologically replacement doses of glucocorticoids (0.5 mg/kg/day of prednisone or equivalent doses of other corticosteroids).8) There are no cases of uncontrolled fungal, bacterial, viral, or other infections requiring intravenous treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate(ORR) | 3 months | ORR included complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by an Independent Review Committee（IRC） assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum cytokines-INF-γ | 28 days | The concentration levels of Interferon -γ（INF-γ） at each time point . |
| ORR | 3 months | ORR at 3 months after CAR-T-19 infusion as assessed by investigator. |
| Minimal residual disease（MRD） | 3 months | MRD-negative ORR as assessed by Independent Review Committee (IRC) and investigator. |
| Best overall response (BOR) | 2 years | BOR as assessed by Independent Review Committee (IRC) and investigator. |
| Duration of response (DOR) | 2 years | DOR as assessed by Independent Review Committee (IRC) and investigator. |
| Event Free Survival（EFS） | 2 years | EFS as assessed by Independent Review Committee (IRC) and investigator. |
| Recurrence Free Survival（RFS） | 2 years | RFS as assessed by Independent Review Committee (IRC) and investigator. |
| Overall survival (OS) | 2 yeas | Overall survival means the time from infusion of CAR-T-19 cells to death of participants from any cause. |
| AE safety | 2 years | Number of participants with Adverse event (AE). |
| SAE safety | 2 years | Number of participants with Serious adverse event (SAE) |
| Serum cytokines-TNF-α | 28 days | The concentration levels of tumor necrosis factor -α（ TNF-α） at each time point . |
| RCL safety | 15 years | Number of participants with Replication Competent Lentivirus (RCL). |
| Pharmacokinetics (PK) Parameter-Cmax | 2 years | Cmax |
| Pharmacokinetics (PK) Parameter-Tmax | 2 years | Tmax |
| Pharmacokinetics (PK) Parameter-AUC0-t | 2 years | AUC0-t |
| Pharmacokinetics (PK) Parameter- AUC0-28d | 2 years | AUC0-28d |
| Pharmacokinetics (PK) Parameter- t1/2 | 2 years | t1/2 |
| Pharmacodynamics | 2 years | The degree of clearance of CD19-positive B cells at different blood collection time points after cell infusion. |
| Serum cytokines-Interleukin 6 | 28 days | The concentration levels of Interleukin 6（ IL-6）at each time point . |
| Serum cytokines-Interleukin 10 | 28 days | The concentration levels of Interleukin 10（ IL-10）at each time point . |
| ADA safety | 2 years | Number of participants with Anti-drug antibody(ADA). |
Countries
China
Contacts
Primary ContactXiaofan Zhu
Outcome results
None listed