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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase 1/2 Study Evaluating the Safety and Efficacy of the Combination of Anti-CD19 Chimeric Antigen Receptor-Modified T Cell (CAR-T) Therapy and Hematological Stem Cell Transplantation (HSCT) for MRD+ B-cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03366324
• Other study ID #: CART-CD19-03
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 1, 2016
• Est. completion date: June 1, 2021

Study information

• Verified date: November 2018
• Source: Wuhan Sian Medical Technology Co., Ltd
• Contact: YU HU, M.D., Ph.D
• Phone: 86-13986183871
• Email: dr_huyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 1, 2021
• Est. primary completion date: January 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• B Cell Lymphoma
• Leukemia, Lymphoid
• Lymphoma, B-Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Genetic:
• Second generation CAR-T cells
Patients receive CD19 CAR-T cells transduced with a lentiviral vector on days 0, 1, and 2.

Procedure:
• Hematological stem cell transplantation
Patients receive hematological stem cell transplantations within 3 months after they achieve MRD- remissions after CAR-T therapies.

Locations

Country	Name	City	State
China	Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (5)

Lead Sponsor	Collaborator
Wuhan Sian Medical Technology Co., Ltd	Jingzhou Central Hospital, The First People's Hospital of Yuhang District, Wuhan Union Hospital, China, Xiangyang Central Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of study related adverse events	defined as >= Grade 3(NCI CTCAE version 4.03) signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment	200 days from enrollment
Secondary	Number of participants with an MRD negative complete remission after CAR-T therapy and HSCT	the efficacy of the combination of CAR-T therapy and HSCT will be estimated based on the number of participants who have an MRD negative (flow cytometry) bone marrow aspirate following the treatment	2 years from enrollment