Anti-CD19 U-CAR-T Cell Therapy for B Cell Hematologic Malignancies

B-cell Lymphoma Clinical Trial

Official title:

Anti-CD19 Universal CAR-T Cells for CD19+ B Cell Hematologic Malignancies: a Multi-center, Uncontrolled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04264039
• Other study ID #: antiCD19-UCAR-T
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: April 1, 2020
• Est. completion date: April 1, 2022

Study information

• Verified date: February 2020
• Source: Xinqiao Hospital of Chongqing
• Contact: Xi Zhang, MD
• Phone: +8613808310064
• Email: zhangxxi[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The stunning response rate of anti-CD19(cluster of differentiation antigen 19) auto-CAR(chimeric antigen receptor)-T cell therapy brings hope to patients with relapsed or refractory B-cell hematologic malignancies. However, based on open clinical trials, using patients' T cells might encounter the failure of apheresis available T cells, even if successful, the time needed for the manufacture could also cause the irreversible disease progress. Furthermore, the cost of auto-CAR-T cells is not affordable for most patients. So to provide an accessible and affordable anti-CD19 CAR-T cell therapy for patients with B-cell hematologic malignancies, we launch such a trial that using the edited T cells from healthy donors to manufacture universal CAR-T cells and adapt it in patients with CD19+ B-cell leukemia or lymphoma.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: April 1, 2022
• Est. primary completion date: April 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 70 Years

Eligibility

Inclusion Criteria:

• 1. Diagnosis of recurrent B-cell acute lymphoblastic leukemia (B-ALL), B-cell acute lymphoblastic lymphoma (B-LLy), or B-non-Hodgkin lymphoma (B-NHL)

2. CD19-positive tumor (=20% CD19 positive blasts by flow cytometry or immunohistochemistry (tissue))

3. Hgb = 7.0 (can be transfused)

4. Life expectancy greater than 12 weeks

5. Informed consent explained to, understood by and signed by the patient/guardian. The patient/guardian is given a copy of informed consent.

Exclusion Criteria:

1. Pregnant or lactating.

2. Tumor in a location where enlargement could cause airway obstruction (per investigator discretion).

3. Active infection with HIV or HTLV.

4. Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6.

5. Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment).

6. CNS abnormalities: Presence of CNS(central nervous system)-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF(cerebrospinal fluid) with = 5 WBC( white blood cell)s per mm3 (unless negative by the Steinherz/Bleyer algorithm); Presence of any CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia
• B-cell Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• anti-CD19 UCAR-T cells
Dose range:1 to 5 ×10^7 cells/Kg, Dose level one: 1×10^7 cells/Kg, Dose level two: 3×10^7 cells/Kg, Dose level three:5 ×10^7 cells/Kg

Drug:
• Fludarabine
30mg/m^2 per day for 6 days
• Cytoxan
300mg/m^2 per day for 2 to 6 days determined by tumor burden at baseline
• Melphalan
50 to 70 mg/m^2 in total for 1 or 2 days, whether to use determined by tumor burden at baseline

Locations

Country	Name	City	State
China	Department of Hematology, Xinqiao Hospital	ChongQing	Chongqing

Sponsors (13)

Lead Sponsor

Collaborator

Xinqiao Hospital of Chongqing

920th Hospital of Joint Logistics Support Force, Central South University, Fujian Medical University Union Hospital, Gracell Biotechnologies (Shanghai) Co., Ltd, Nanfang Hospital of Southern Medical University, Second Affiliated Hospital of Xi'an Jiaotong University, Tang-Du Hospital, The Affiliated Hospital Of Guizhou Medical University, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Kunming Medical College, The General Hospital of Western Theater Command, The Second Affiliated Hospital of Chongqing Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the anti-tumor efficiency of anti-CD19 UCAR-T cells	ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value	4 weeks after infusion
Secondary	the long-term efficiency of anti-CD19 UCAR-T cells	ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value	3 and 6 months after infusion