Phase I, interventional, single-arm, open-label, treatment study to evaluate the safety and effectiveness of CD33-CLL1 CAR in patients with relapsed and/or refractory acute myeloid leukemia (AML).
AML bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CLL1 expression comprise a rare population that also plays an important role in disease progression and relapse for myeloid malignancies. CD33 is widely expressed in AML. Targeting both CD33 and CLL1 surface antigens together may offer two distinct benefits. First, targeting both bulk disease and leukemic stem cells together allows for a more comprehensive ablation of the disease. Second, dual targeting of myeloid malignancies by both CD33 and CLL1 directed therapy overcomes the pitfalls of single-antigen therapy by preventing relapse due to antigen loss. While loss of a single antigen under antigen-specific selection pressure is possible, loss of two antigens simultaneously is much less likely. CD33-CLL1 CAR is a compound Chimeric Antigen Receptor immunotherapy with two distinct functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1 and CD33. CD33-CLL1 CAR intends to target the mechanisms of single-CAR relapse, specifically antigen escape and leukemic stem cells.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
recommendation: 30mg/m2 (D-5\~D-3),determined by tumor burden at baseline.
recommendation: 300-500mg/m2 (D-5\~D-3),determined by tumor burden at baseline.
CD33-CLL1 CAR-T infusion (starting at dose level 1 \[DL1\]: 0.5 x 106 transduced CAR-T cells/kg) on Day 0.
Department of Hematology, Xinqiao Hospital
Chongqing, Chongqing Municipality, China
Overall Response Rate (ORR)
Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CRi), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies
Time frame: 4 weeks after infusion
the safety evaluation of Dual CD33-CLL1 CAR-T cells
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: within 4 weeks after infusion
Progression-free survival (PFS)
Surviavl without disease progression
Time frame: up to 2 years after infusion
Overall survival(OS)
Surviavl
Time frame: up to 2 years after infusion
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