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

Sponsor

Xinqiao Hospital of Chongqing (Other)

Overall Status

Unknown status

CT.gov ID

NCT04264039

Collaborator

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

Enrollment

Location

Arm

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
B-cell Acute Lymphoblastic Leukemia B-cell Lymphoma	Biological: anti-CD19 UCAR-T cells Drug: Fludarabine Drug: Cytoxan Drug: Melphalan	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2020

Anticipated Primary Completion Date :

Apr 1, 2021

Anticipated Study Completion Date :

Apr 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: anti-CD19 UCAR-T cells After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD19 UCAR-T cells between 1 and 5 ×10^7 cells/Kg will be evaluated	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 Drug: Cytoxan 300mg/m^2 per day for 2 to 6 days determined by tumor burden at baseline Drug: Melphalan 50 to 70 mg/m^2 in total for 1 or 2 days, whether to use determined by tumor burden at baseline

Arm

Intervention/Treatment

Experimental: anti-CD19 UCAR-T cells

After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD19 UCAR-T cells between 1 and 5 ×10^7 cells/Kg will be evaluated

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

Drug: Cytoxan

300mg/m^2 per day for 2 to 6 days determined by tumor burden at baseline

Drug: Melphalan

50 to 70 mg/m^2 in total for 1 or 2 days, whether to use determined by tumor burden at baseline

Outcome Measures

Primary Outcome Measures

the anti-tumor efficiency of anti-CD19 UCAR-T cells [4 weeks after infusion]
ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value

Secondary Outcome Measures

the long-term efficiency of anti-CD19 UCAR-T cells [3 and 6 months after infusion]
ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

CD19-positive tumor (≥20% CD19 positive blasts by flow cytometry or immunohistochemistry (tissue)）
Hgb ≥ 7.0 (can be transfused)
Life expectancy greater than 12 weeks
Informed consent explained to, understood by and signed by the patient/guardian. The patient/guardian is given a copy of informed consent.

Exclusion Criteria:

Pregnant or lactating.
Tumor in a location where enlargement could cause airway obstruction (per investigator discretion).
Active infection with HIV or HTLV.
Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6.
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).
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Hematology, Xinqiao Hospital	ChongQing	Chongqing	China	400037

Sponsors and Collaborators

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