B-ALL Clinical Trial
Official title:
Safety and Efficiency of Anti-CD19/CD22 Tandem Fully Human Chimeric Antigen Receptor (CAR)-Transduced T-cell Therapy for Pediatric and Young Adult Patients With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia: a Single Centre, Non-randomised, Open Label Phase I-II Clinical Trial of Automatically Produced Cell Therapy Product MB-CAR-T19-22 Using CliniMACS Prodigy
The purpose of this study is to evaluate the safety and efficiency of autologous CD19/CD22 CAR-T lymphocytes in a cohort of pediatric and young adult patients with relapsed /refractory B-lineage acute lymphoblastic leukemia
Status | Active, not recruiting |
Enrollment | 50 |
Est. completion date | March 13, 2027 |
Est. primary completion date | March 13, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 3 Months to 25 Years |
Eligibility | Inclusion Criteria: - Ability to give informed consent (for patients > 14 years old). For subjects < 18 years old their legal guardian must give informed consent - CD19 or CD22 expression must be detected on greater than 50% of leukemic cells by flow cytometry - Presence of a measurable mass of tumor cells in the bone marrow or extramedullary sites at the time of patient's inclusion in the study - Patients with relapsed or refractory CD19 and CD22-expressing B-cell ALL: - Induction failure - MRD = 0,1% after 2nd chemotherapy course for high-risk group patients. - First bone marrow or combined relapse of acute lymphoblastic leukemia, no CR or MRD = 0,1% after 1-course 2nd line therapy - Second and further relapse of ALL - Relapse or MRD = 0,1% of ALL after hematopoietic stem cell transplant (> 60 days post alloHSCT)o There must be no available alternative approved curative therapies - Patient Clinical Performance Status: Karnofsky >50% or Lansky >50% - Patient Life Expectancy > 4 weeks - Patients recovered from acute toxic effects of prior chemotherapy, immune- or radiotherapy - Patient absolute blood naïve (CD45RA+) T-lymphocyte count = 50/mm3 - Patient cardiac function left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO. - Patients who agree to long-term follow up for up to 5 years (if received CD19/CD22 CAR-T cell infusion) - March 2021 amendment: Healthy HLA-matched related or haploidentical donor (only for HSCT cohort) Exclusion Criteria: - <50% expression of both CD19 and CD22 on the leukemic population - Active (detectable viremia) hepatitis B, C or HIV infection - Oxygen saturation = 90% - Bilirubin >3x upper norma limit - Creatinine >3x upper norma limit - Active acute GVHD overall grade =2 (Seattle criteria) - Moderate/severe chronic GVHD (NIH consensus) requiring systemic steroids - Clinical signs of grade > 3 CNS disorders (seizure disorder, paresis, aphasia, cerebrovascular, ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder) - Pregnant or lactating women. - Active (unresolved) severe infection |
Country | Name | City | State |
---|---|---|---|
Russian Federation | Federal Research Institute of Pediatric Hematology, Oncology and Immunology | Moscow |
Lead Sponsor | Collaborator |
---|---|
Federal Research Institute of Pediatric Hematology, Oncology and Immunology |
Russian Federation,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | incidence of grade 3-5 SAE | Safety:
Toxicity evaluation following CD19/CD22 CAR T-cell infusion: - incidence of grade 3-5 SAE (according CTCAE v.5.0) |
1 month | |
Primary | incidence of grade 3-5 Severe Cytokine Release Syndrome | Safety:
Toxicity evaluation following CD19/CD22 CAR T-cell infusion: - incidence of grade 3-5 Severe Cytokine Release Syndrome (according ASTCT consensus) |
1 month | |
Primary | incidence of grade 3-5 ICANS | Safety:
Toxicity evaluation following CD19/CD22 CAR T-cell infusion: - incidence of grade 3-5 ICANS (according to ASTCT consensus) |
1 month | |
Primary | Rate of complete remission | Efficacy:
- Rate of complete remission among all enrolled patients (Intent-to-Treat population) |
1 month | |
Primary | Rate of MRD-negative remission | Efficacy:
- Rate of MRD-negative remission among all patients (Intent-to-treat population) |
1 month | |
Primary | March 2021 amendment: incidence of graft failure before day 100 (only for HSCT cohort) | Safety: | 100 days | |
Primary | March 2021 amendment: incidence of aGVHD grade 2-4 (only for HSCT cohort) | Safety: | 100 days | |
Secondary | Duration of MRD-negative remission | Efficacy: | 2 years | |
Secondary | Persistence/frequency of CD19/CD22 lymphocytes in peripheral blood (flow cytometry) | Efficacy: | 2 years | |
Secondary | Duration of B-cell aplasia and hypogammaglobulinemia | Efficacy: | 2 years | |
Secondary | Overall survival | Efficacy: | 5 years | |
Secondary | Safety and adverse effects long-term | Safety: | 5 years | |
Secondary | March 2021 amendment: Incidence of chronic GVHD (only for HSCT cohort) | Safety: | 5 years |
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