Anti-CD19 CAR-T Therapy Combine With HSCT to Treat MRD+ B-cell Malignancies

Wuhan Sian Medical Technology

Status and phase: Unknown; Phase 2; Phase 1

Conditions: B Cell Lymphoma; Acute Lymphoblastic Leukemia

Treatments: Procedure: Hematological stem cell transplantation; Genetic: Second generation CAR-T cells

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03366324

CART-CD19-03

Details and patient eligibility

About

For micro residual disease (MRD) positive patients who have undergone at least 2 cycles chemotherapies for their CD19+ B-cell malignancies, there would be much more risks for them to receive hematological stem cell transplantation (HSCT) than MRD- patients. In order to reduce HSCT-related adverse events for these kind of patients, investigators plan to conduct CAR-T therapies on them first to make them achieve MRD- statuses, and then transfer them to HSCT.

Full description

In order to improve prognoses for MRD+ patients who have undergone at least 2 cycles chemotherapies, patients will receive CAR-T therapy before HSCT, once they achieve MRD- remissions, they will subsequently receive HSCT if there are no contraindications.

Enrollment: 20 estimated patients

Sex: All

Ages: Under 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. The patient is pathologically and histologically confirmed as CD19 + B cell tumors, and has no effective treatment options currently, such as chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT); or patients voluntarily choose CD19 CAR-T cells as a first treatment;

2. The patient is MRD+ (<10%) after at least two cycles of chemotherapies.

3. B cell hematological malignancies include the following three categories:

   • B-cell acute lymphocytic leukemia (B-ALL);
   • Indolent B-cell lymphoma (CLL, FL, MZL, LPL);
   • Aggressive B-cell lymphoma (DLBCL, BL, MCL);

4. < 70 years old;

5. Expected survival time > 6 months;

6. Female patients around childbearing age, negative pregnancy test before trial, and agreed to take effective contraceptive measures during the trial until the last visit;

7. Voluntarily participate in this experiment and sign informed consent by themselves, or legally authorized representative.

Exclusion criteria

1. With a history of allo-HSCT;
2. With a history of epilepsy or other central nervous system diseases;
3. The presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within recent six months, or heart disease with cardiac function in any grade 3 (moderate) or 4 ( severe) (according to the New York Heart Association (NYHA) Functional Classification System);
4. Pregnant or lactating women (safety of this therapy for the unborn child is unknown);
5. Not curable active infection;
6. Patients with active hepatitis B or hepatitis C virus infection;
7. Combined use of systemic steroids within two weeks (except use of inhaled steroid recently or currently);
8. Using product of gene therapy before;
9. Creatinine> 2.5 mg / dl (221.0 umol/L); ALT / AST> 3 X the normal amount; Bilirubin> 2.0 mg / dl (34.2 umol/L);
10. Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;
11. Patients with HIV-infection;
12. Any situation that may increase the risk of patients or interfere with test results.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Combination of CAR-T therapy and HSCT

Experimental group

Description:

After patients achieve MRD- remissions through Second generation CAR-T cells, they will subsequently receive hematological stem cell transplantations within 30 days.

Treatment:

Procedure: Hematological stem cell transplantation

Genetic: Second generation CAR-T cells