CAR2219 CAR-T Cells for the Treatment of R/R B Cell Leukemia and Lymphoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age14-75
SponsorAffiliated Hospital to Academy of Military Medical Sciences
About this trial
This is a single arm study to evaluate the safety and efficacy of CAR2219 CAR-T cells in the treatment of relapsed/refractory CD19/CD22 positive B cell Leukemia and Lymphoma.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Signed written informed consent;
Relapsed/refractory CD19/CD22 positive B cell Leukemia or Lymphoma must be assured and meet one of the following conditions: (1) Confirmation for either CD19 or CD22 positivity using immunohistochemistry or flow cytometry; (2) B-cell tumors include the following three categories: ① B-cell acute lymphoblastic leukemia (B-ALL); Indolent B-cell lymphoma (CLL, FL, MZL, LPL, HCL); Aggressive B-cell lymphoma (DLBCL, BL, MCL) (3) Refractory/recurrent B-ALL (include one of the following situations) : ① relapse within 12 months after the first remission; ② The first refractory patients who did not achieve complete remission after 2 cycles of standard chemotherapy regimen; ③ Failure to achieve complete remission or relapse after first-line or multi-line salvage chemotherapy; ④ Recurrence after hematopoietic stem cell transplantation. (4) Refractory/recurrent B-cell lymphoma (meeting the requirements of 1 of the first 4 below plus 5) : ① After 4 courses of chemotherapy prescribed by the standard protocol, the tumor has shrunk by less than 50% or the disease progression(PD); ② CR reached after standard chemotherapy, but relapse occurred within 12 months; ③ Two or more recurrence after CR; ④ Recurrence after hematopoietic stem cell transplantation; ⑤Patients must have received rituximab or another anti-CD20 monoclonal antibody (unless Investigator determines that tumor is CD20-negative) and an anthracycline-containing chemotherapy regimen.
All genders, ages: 14 to 75 years
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
Disqualifiers
Severe heart failure with left ventricular ejection fraction <50%;
A history of severe lung function impairment;
Combined with other advanced malignant tumors;
Complicated with severe infection that could not be effectively controlled;
Trial design
Design model
Single group
Treatments tested in this trial
CAR2219-T cells
GeneticGenetic: CAR2219-T cells Each subject will be infused with single dose of CD2219-CAR-T cells. A classic "3+3" dose escalation will be employed. The low dose is 5×10\^5 /kg, the medium dose is 1×10\^6 /kg, and the high dose is 2×10\^6 /kg. Drug: Fludarabine Fludarabine will be given at a dose of 30 mg/m2/day intravenously (IV) for 3 days prior to the infusion of CD2219-CAR-T cells. Drug: Cyclophosphamide Cyclophosphamide will be given at a dose of 300 mg/m2/day intravenously (IV) for 3 days prior to the infusion of CD2219-CAR-T cells.
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: This is a single arm treatment of CAR2219 CAR-T cell.Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
According to the incidence of treatment-related adverse events (AEs) to evaluate the safetyof CAR2219 CAR-T cells in the treatment of relapsed/refractory CD19+CD22+ B-cell Leukemia and Lymphoma.
Incidence of treatment-related adverse events (AEs) Description: Number and severity of adverse events graded according to CTCAE v5.0, including cytokine release syndrome (CRS) graded by ASTCT criteria and immune effector cell-associated neurotoxicity syndrome (ICANS) graded by ASBMT criteria
Time frame
up to 2 years2
According to the determine the Maximal Tolerable Dose(MTD) to evaluate the safetyof CAR2219 CAR-T cells in the treatment of relapsed/refractory CD19+CD22+ B-cell Leukemia and Lymphoma.
Time frame
MTD will be determined based on DLTs observed during the first 28 days of study treatment.Secondary outcomes
1
According to the objective response rate (ORR) to evaluate the efficacy of CAR2219 CAR-T cells in the treatment of relapsed/refractory CD19+CD22+ B-cell Leukemia and Lymphoma.
Overall response rate (ORR) Description: Proportion of participants achieving complete response (CR) or partial response (PR) according to Lugano 2014 criteria for lymphomas and NCCN guidelines for leukemias, assessed via bone marrow biopsy (for leukemia) and PET/CT imaging (for lymphoma)
Time frame
Within 3 months following infusion of CAR2219 CAR-T cellsOther outcomes
1
CAR-T cell expansion kinetics
Peak CAR-T cell levels (Cmax) and persistence duration measured by flow cytometry and qPCR in peripheral blood
Time frame
Up to 12 months after CAR-T treatment2
CAR-T cell clonality dynamics
Single-cell sequencing was performed to track the clonal evolution of CAR-T cells in patients at 14 days, 1 month, 3 months, 6 months, 1 year, and 2 years post-infusion.
Time frame
Up to 24 months after CAR-T treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov