A Phase 1 interventional study of Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells in Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia and Non Hodgkin's Lymphoma, sponsored by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Status unknown at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-04-08.
Sponsored by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology · Phase 1, Interventional, and Treatment
This is a single-center, open-label, single-arm study to evaluate the primary safety and efficacy of anti-CD19 chimeric antigen receptor(CAR)-modified NK cells(CAR-NK-CD19) in patients with relapsed or refractory hematological malignancies.
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations.
Cord blood(CB) derived NK cells from healthy donor are the source for production of CAR-NK-CD19 cells. CB derived NK cells are purified and transduced with a retroviral vector encoding the anti-CD19 CAR and interleukin-15.
This is an investigational study. The objectives are to evaluate the safety and efficacy of CAR-NK-CD19 cells in patients with CD19+ B-cell malignancies.
2,121 studies on the registry are indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma; 492 are open to participants now.
This study's planned enrollment of 27 is below the median of 40 across 1,691 interventional studies indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma.
Browse Precursor Cell Lymphoblastic Leukemia-Lymphoma studies →Union Hospital, Tongji Medical College, Huazhong University of Science and Technology is the lead sponsor of 172 studies on the registry; 136 are open to participants now.
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Patient's main organs functioning well:
A. Liver function: alanine aminotransferase/aspartate aminotransferase \< 2.5 times the upper limit of normal (ULN) and total bilirubin≤ 1.5 times ULN; B. Renal function: Creatinine clearance rate ≥ 60ml/min. C. Pulmonary function: Indoor oxygen saturation ≥ 95%. D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥50%, no clinically-significant ECG findings.
Exclusion Criteria:
Patients will received lymphodepletion with fludarabine (30 mg/kg) and cyclophosphamide (300 mg/kg) on day -5, -4, and -3, followed by one infusion of CAR-NK-CD19 cells on day 0. The study will be divided into three groups: Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, and Non Hodgkin's Lymphoma. Doses of 0.01×10\^7, 0.1×10\^7, 1.0×10\^7 CAR+ T cells (with an allowance of ±20%) will be tested in each group in the 3+3 dose-escalation study. Each dose group has 3 patients. If no dose-limited toxicity (DLT) emerges in the group, then the subsequent higher dose will be used in the next group. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level. The maximum dose could be extended.
Drug: Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells
fludarabine 30 mg/kg on day -5, -4, and -3; cyclophosphamide 300 mg/kg on day -5, -4, and -3; CAR-NK-CD19 Cells on day 0.
Incidence of Treatment-related Adverse Events
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Time frame: within 2 years after infusion
Overall response rate(ORR) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
ORR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 years after infusion
Complete response rate(CRR) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 years after infusion
Progress-free survival(PFS) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 years after infusion
Duration of Response(DOR) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 years after infusion
Overall survival(OS) of administering CAR-NK-CD19 cells in Relapsed/Refractory CD19+ B-cell hematological malignancies.
OS will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time frame: within 2 years after infusion
In vivo expansion and survival of CAR-NK-CD19 cells
Quantity of CAR-NK-CD19 CAR copies in bone marrow and peripheral blood will be determined by using quantitative polymerase chain reaction.
Time frame: within 2 years after infusion
Plan to share: No
Start is estimated for Apr 2021; primary completion for Mar 2023, 23 months later.
Of 167 non-industry phase 1 interventional studies under Precursor Cell Lymphoblastic Leukemia-Lymphoma, half reached primary completion within 57 months of starting (the median), counting those still running; a quarter within 38 and three quarters within 90. This study's planned 23 months is below that.
Counting every sponsor, half of 234 studies reached it within 55 months; a quarter within 34 and three quarters within 89.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in Apr 2021. You cannot join it, but the record below documents what was studied.
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