## Protocol Section
### Identification Module
**NCT ID:** NCT05639179

**Brief Title:** Novel Anti-CD19 Universal CAR-T Cells for r/r CD19+ B-ALL

**Official Title:** An Investigator-initiated Trial to Evaluate the Efficacy and Safety of Anti-CD19 Universal CAR-T Cells in the Treatment of Relapsed/Refractory(r/r) CD19+ B-cell Acute Lymphoblastic Leukemia(B-ALL)

#### Organization Study ID Info
**ID:** KM-010
#### Organization
**Class:** OTHER
**Full Name:** 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
### Status Module
#### Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-12-08

**Type:** ACTUAL

**Last Update Submit Date:** 2022-12-07

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-12-05

**Type:** ACTUAL

**Status Verified Date:** 2022-12

#### Study First Post Date
**Date:** 2022-12-06
**Type:** ACTUAL
**Study First Submit Date:** 2022-11-25
**Study First Submit QC Date:** 2022-11-25
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This is a single-arm, single-center, open-labeled clinical study to evaluate the safety and efficacy of UCAR-T Cells injection for patients with relapsed/refractory(r/r) B-cell Acute Lymphoblastic Leukemia(B-ALL).

**Detailed Description:** Although the anti-CD19 CAR-T cell therapies have gained significant clinical outcome in patients with r/r B-ALL，autologous CAR-T is not feasible for some patients. To make further improvement, the investigators are going to conduct a clinical trial using universal CAR-T(UCAR-T) cells targeting CD19 for r/r B-ALL patients.

After enrollment, patients will get a 3-5 days lymphodepletion therapy, then the UCAR-T Cells will be infused by vein. Subjects will be followed for safety and efficacy up to 12 weeks. For those with a durable remission 12 weeks after infusion, the follow-up will last for at least 12 months for disease control.

### Conditions Module

**Conditions:**

- B-cell Acute Lymphoblastic Leukemia

- B-ALL

**Keywords:**

- universal CAR-T(UCAR-T)

- CD19

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Subjects who meet the enrollment conditions will receive intravenous infusion of UCAR-T Cells after lymphodepletion.

**Intervention Names:**

- Biological: UCAR-T Cells

**Label:** Assigned Interventions

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Assigned Interventions

**Description:** UCAR-T Cellswill be administered by vein. The trial includes two portions. The first portion is a"3+3"dose escalation study, in which three dose groups are set:Dose level one:1×10\^6 cells/kg;Dose level two:2×10\^6 cells/kg;Dose level three:5×10\^6 cells/kg. Each dose group requires at least three subjects. The trial will start from dose level one. The second portion includes a dosage extended cohort and will start after the finish of the"3+3"dose escalation study. Twelve subjects will get infusion of UCAR-T Cells at the best dose verified in the first portion.

**Name:** UCAR-T Cells

**Type:** BIOLOGICAL

### Outcomes Module

#### Primary Outcomes

**Description:** Neurotoxicity and/or CRS≥G3.

**Measure:** Dose-limiting toxicity (DLT)

**Time Frame:** Up to 28 days after infusion

**Description:** The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included.

**Measure:** Incidence of Treatment Related adverse events (AEs)

**Time Frame:** Up to 12 months after infusion

#### Secondary Outcomes

**Description:** The persistence over time of CAR-T cells in the peripheral blood as determined by flow cytometry and qPCR.

**Measure:** Persistence of CAR-T cells

**Time Frame:** Up to 24 weeks after infusion

**Description:** Patients who achieve CR(complete response) or CRi after infusion

**Measure:** Objective response rate (ORR)

**Time Frame:** At 4,8,12 weeks after infusion

**Description:** Progression-free survival (PFS) is the time between the time a patient with tumor disease receives treatment and the time between the observation of disease progression or death from any cause.

**Measure:** Progression-free survival (PFS)

**Time Frame:** Up to 24 weeks after infusion

**Description:** Overall survival (OS) is the time from randomization to death from any cause.

**Measure:** Overall survival (OS)

**Time Frame:** Up to 24 weeks after infusion

**Description:** Duration of remission (DOR) is the time from the first detection of CR or PR to the discovery of PD.

**Measure:** Duration of remission (DOR)

**Time Frame:** Up to 24 weeks after infusion

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Male or female, aged 2-75 years;
2. A definite diagnosis of relapsed/refractory B-ALL and a percentage of primitive/naive lymphocytes \>5% in bone marrow at baseline (flow cytometry);
3. CD19 expression was positive in bone marrow or peripheral blood tumor cells;
4. ECOG score 0-2 points;
5. Expected survival time ≥3 months;
6. Adequate liver, kidney, heart and lung function;
7. Patients who have recovered from acute toxic effects of prior chemotherapy should be excluded from the trial at least one week apart;
8. Women of childbearing age have negative blood pregnancy test before the start of the trial, and agree to take effective contraceptive measures during the trial until the last follow-up; male subjects with partners of childbearing potential agree to take effective contraceptive measures during the trial until the last follow-up;
9. Voluntarily sign the informed consent.

Exclusion Criteria:

1. Presence of other concurrent active malignancy;
2. People with severe mental disorders;
3. A history of any of the following genetic disorders, such as Fanconi anemia, Schu-Day syndrome, Gerstmann syndrome, or any other known bone marrow failure syndrome;
4. Acute GVHD of grade II-IV or extensive chronic GVHD;
5. Had grade III-IV heart failure or myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically prominent heart disease within one year prior to enrollment;
6. The presence of any indwelling catheter or drainage (e.g., percutaneous nephrostomy, indwelling catheter, bile drainage, or pleural/peritoneal/pericardial catheter), except for patients who are permitted to use dedicated central venous catheters;
7. A history or disease of the central nervous system(CNS), such as seizure disease, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the CNS;
8. Human immunodeficiency virus (HIV) seropositivity; Hepatitis B surface antigen positive or hepatitis B core antibody positive, and HBV-DNA positive; Patients with hepatitis C (HCV-RNA quantitative test results positive); Or the presence of other serious active viral or bacterial infections or uncontrolled systemic fungal infections;
9. Patients with severe history of allergy or allergic constitution;
10. A history of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) leading to end-organ damage or requiring systemic immunosuppressive/systemic disease modulating drugs within the past 2 years;
11. Had or is suffering from interstitial lung disease (e.g., pneumonia, pulmonary fibrosis);
12. Had undergone other clinical trials in the 4 weeks prior to participating in this trial;
13. Poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan;
14. For patients contraindicated with cyclophosphamide and fludarabine chemotherapy;
15. Subjects requiring systemic corticosteroid therapy (prednisone ≥5mg/ day or equivalent dose of another corticosteroid) or other immunosuppressive agents within 1 month after UCAR-T cell reinfusion, except for adverse events;
16. Receiving donor lymphocyte infusion within 6 weeks before enrollment;
17. Pregnant and lactating women;
18. Any other condition that the investigator deemed inappropriate for inclusion.

**Maximum Age:** 75 Years

**Minimum Age:** 2 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Sanbin1011@163.com

**Name:** Wang Sanbin, Doctor

**Phone:** 13187424131

**Phone Ext:** +86

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Kunming

**Contacts:**

***Contact 1:***

- **Name:** Chen Li

- **Phone:** 64774206

- **Phone Ext:** 0871

- **Role:** CONTACT

**Country:** China

**Facility:** 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

**State:** Yunnan

**Status:** RECRUITING

**Zip:** 650000

#### Overall Officials

**Official 1:**

**Affiliation:** 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

**Name:** Wang Sanbin, Doctor

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000008206

- Term: Lymphatic Diseases

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M10951

- Name: Leukemia, Lymphoid

- Relevance: HIGH

- As Found: Lymphoblastic Leukemia

- ID: M27585

- Name: Precursor Cell Lymphoblastic Leukemia-Lymphoma

- Relevance: HIGH

- As Found: Acute Lymphoblastic Leukemia

- ID: M11220

- Name: Lymphoma

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T175

- Name: Acute Lymphoblastic Leukemia

- Relevance: HIGH

- As Found: Acute Lymphoblastic Leukemia

- ID: T3533

- Name: Lymphoblastic Lymphoma

- Relevance: HIGH

- As Found: Acute Lymphoblastic Leukemia

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T3543

- Name: Lymphosarcoma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007938

- Term: Leukemia

- ID: D000054198

- Term: Precursor Cell Lymphoblastic Leukemia-Lymphoma

- ID: D000007945

- Term: Leukemia, Lymphoid

### Misc Info Module

- Version Holder: 2024-05-24
