Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT03098355 |
| Other study ID # |
anti-CD19/22 CART Cells |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
December 30, 2017 |
| Est. completion date |
December 31, 2023 |
Study information
| Verified date |
September 2022 |
| Source |
Zhujiang Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Clinical studies of CD19 CAR-T cells in the treatment of blood and lymphatic system tumors
have achieved unprecedented successes. Because of the heterogeneity of the tumor, patients
often carry CD19-negative tumor cell clones that express alternative target antigens (such as
CD22, CD20 and CD123). In order to effectively eradicate all tumor clones and prevent
recurrence, alternative tumor antigens besides CD19 are considered for CAR-T cell targeting.
In this tudy, autologous T cells are genetically modified with 4th generation anti-CD19 and
anti-CD22 CARs (4SCAR19/22) using lentiviral vectors. For safety consideration, the 4SCAR is
engineered with an inducible caspase 9 self-withdrawal genetic design that allows for rapid
elimination of the infused CAR-T cells. Interleukin-2 has been shown to boost immune response
against leukemia cells. The serum interleukin-6 level will be monitored and when it returns
to normal range by day 28 after CAR-T cell infusion, patients will receive subcutaneous
injection of interleukin-2, and evaluated for 24 months for safety, efficacy and persistence
of CAR T cells.
Description:
Objectives:
1. Primary Outcome Measures:
1. Evaluate the frequency and severity of adverse events, including, but not limited
to, cytokine release syndrome (CRS) [ Time Frame: From date of dosing ( day 1 ) up
to 50 weeks ]
2. Evaluate grade 3 and higher toxicity rate of patients (toxicity possibly attributed
to 4SCAR19/22 T cells)
3. Evaluate the safety and effect of administration of 4SCAR19/22 T cells followed by
interleukin-2 in treating pediatric patients with relapsed and refractory B cell
malignancies.
2. Secondary:
1. Evaluate Overall Complete Remission Rate (ORR).
2. Evaluate overall response rate including complete remission (CR) and complete
remission with incomplete blood count recovery (CRi) .
3. Evaluate duration of remission (DOR).
4. To evaluate the incidence and the treatment effect of cytokine release syndrome
(CRS).
5. To determine the expansion and functional persistence of 4SCAR19/22 T cells in the
peripheral blood of patients and the correlation with antitumor effects;
Design:
1. In this single-center, open-label, nonrandomized, no control, prospective clinical
trial, a total of 30 patients with resistant or refractory B cell acute lymphoblastic
leukemia (ALL) or non-hodgkin's lymphoma (NHL) will be enrolled. Patients with ALL will
be diagnosed according to bone marrow morphology, immunophenotype, cytogenetic and
molecular examination. Patients with NHL will be diagnosed according to bone marrow
morphology, biopsy pathology and imaging examination.
2. Peripheral blood mononuclear cells (PBMC) will be obtained by apheresis, and T cells
will be activated and modified to express the 4SCAR-CD19/22 gene.
3. On Day -2 to -7, PBMC will be activated and enriched for T cells, which will be followed
by 4SCAR-CD19/22 lentiviral transduction. The total culture time is approximately 5-7
days.
4. Patients will receive lymphodepleting chemotherapy composed of cyclophosphamide and
fludarabine prior to cell infusion,
5. Participants will receive the CAR-T cells at a total dose of 0.5-5x10^6/kg.
6. Participants will receive regular subcutaneous injection of interleukin-2 of
250,000iu/m^2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months
after their serum interleukin-6 levels returned to normal range from day 28 after CAR-T
cell infusion.
7. Patients will be monitored for toxicity including cytokine release syndrome, hematologic
toxicities and B-cell aplasia, for response of their underlying malignancy and for CAR-T
cell persistence in the blood, marrow and cerebral spinal fluid (CSF).
