Back to results

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

Primary Purpose

B-cell Acute Lymphoblastic Leukemia, B-cell Lymphoma

Status

Unknown status

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

anti-CD19 UCAR-T cells

Fludarabine

Cytoxan

Melphalan

About this trial

This is an interventional treatment trial for B-cell Acute Lymphoblastic Leukemia

Eligibility Criteria

2 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept 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)
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:

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.

Sites / Locations

Department of Hematology, Xinqiao Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-CD19 UCAR-T cells

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

NCT ID

NCT04264039

First Posted

February 7, 2020

Last Updated

February 7, 2020

Sponsor

Xinqiao Hospital of Chongqing

Collaborators

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, First Affiliated Hospital of Kunming Medical University, The General Hospital of Western Theater Command, Second Affiliated Hospital of Xi'an Jiaotong University, Nanfang Hospital, Southern Medical University, Fujian Medical University Union Hospital, The First Affiliated Hospital of Anhui Medical University, Tang-Du Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04264039

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Unknown status

Study Start Date

April 1, 2020 (Anticipated)

Primary Completion Date

April 1, 2021 (Anticipated)

Study Completion Date

April 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Xinqiao Hospital of Chongqing

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

B-cell Acute Lymphoblastic Leukemia, B-cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

anti-CD19 UCAR-T cells

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

anti-CD19 UCAR-T cells

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

30mg/m^2 per day for 6 days

Intervention Type

Drug

Intervention Name(s)

Cytoxan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Melphalan

Intervention Description

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

Primary Outcome Measure Information:

Title

the anti-tumor efficiency of anti-CD19 UCAR-T cells

Description

ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value

Time Frame

4 weeks after infusion

Secondary Outcome Measure Information:

Title

the long-term efficiency of anti-CD19 UCAR-T cells

Description

ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value

Time Frame

3 and 6 months after infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Xi Zhang, MD

Phone

+8613808310064

Ext

+8613808310064

zhangxxi@sina.com

First Name & Middle Initial & Last Name or Official Title & Degree

Ruihao Huang

Phone

+86 18984398751

1169731117@qq.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xi Zhang, MD

Organizational Affiliation

Xinqiao Hospital of Chongqing

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Hematology, Xinqiao Hospital

City

ChongQing

State/Province

Chongqing

ZIP/Postal Code

400037

Country

China

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs