Clinical trial NCT04303520: Anti-CD19/CD22 Bispecific CAR-T Cell Therapy for CD19-positive ALL
Official title: A Phase I Clinical Trial of T-Cells Targeting CD19 and CD22 for Subjects With CD19-positive Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: CD19-positive ALL
Lead sponsor: The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
Sponsor class: OTHER
Collaborators: name: Hrain Biotechnology Co., Ltd.
name: First Affiliated Hospital of Wenzhou Medical University
name: Second Affiliated Hospital of Nanchang University
First posted: 2020-03-11
Enrollment: 20
Sex: ALL
Minimum age (years): 13
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to study the feasibility and efficacy of anti-CD19/CD22 bispecific chimeric antigen receptors (CARs) T cell therapy for CD19-positive Acute Lymphoblastic Leukemia.

Detailed description: Primary Objectives

1. To determine the feasibility ad safety of anti-CD19/ CD22 CAR-T cells in treating patients with CD19-positive Acute Lymphoblastic Leukemia.

Secondary Objectives

1. To determine in vivo expression, dynamics and persistency of anti-CD19/CD22 CAR-T cells.
2. To determine in vivo expression of CD19-positive B cells.
3. To access the complete remission rate (ORR) in patients with ALL with 3 months after CD19/CD22 CAR-T cells infusion.
4. To investigate the favorable CD19/CD22 CAR-T cells dose and dosage regimen for the Phase II Clinical Trial.

Eligibility criteria: Inclusion Criteria:

1. 13 Years to 70 Years, Male and female;
2. Expected survival \> 12 weeks;
3. Clinical performance status of ECOG score 0-2;
4. Histologically confirmed as CD19-positive lymphoma and who meet one of the following conditions:

   * Patients received at least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
   * Disease recurrence after stem cell transplantation.
5. Accessible to intravenous injection, and no white blood cell collection contraindications
6. Patients who meet the following conditions:

   * Creatinine \< 2.5 mmol/l;
   * Cardiac ejection fraction\>50%, no pericardial effusion and no pleural effusion (ECHO examination);
   * Baseline oxygen saturation\>92%;
   * Total bilirubin≤1.5xULN;
   * ALT/AST≤2.5x normal.
7. Able to understand and sign the Informed Consent Document.

Exclusion Criteria:

1. Accompanied by other malignant tumor
2. Active hepatitis B, hepatitis C, syphilis, HIV infection
3. Suffering severe cardiovascular or respiratory disease
4. Any other diseases could affect the outcome of this trial
5. Any affairs could affect the safety of the subjects or outcome of this trial
6. Pregnant or lactating women, or patients who plan to be pregnancy during or after treatment
7. Occurrence of infection uncontrolled or requiring systemic treatment 14 days prior to assignment
8. Patients who are accounted by researchers to be not appropriate for this test
9. Received CAR-T treatment or other gene therapies before assignment
10. Patients with symptoms of central nervous system
11. Subject suffering disease affects the understanding of informed consent or comply with study protocol.

Primary outcomes:
measure: Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
timeFrame: 6 months
Secondary outcomes:
measure: Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
timeFrame: 8 weeks
measure: Duration of CAR-positive T cells in circulation
timeFrame: 6 months
measure: Total number of CAR-positive T cells infiltrated into lymphoma tissue
timeFrame: 6 months
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Province of TCM
state: Henan
Study officials:
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