Anti-CD19 CAR-T Therapy Bridging to HSCT for CD19+ B-Cell Malignancies

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03366350
• Other study ID #: CART-CD19-02
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 15, 2016
• Est. completion date: June 1, 2021

Study information

• Verified date: May 2019
• 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

This is the second stage of the previous anti-CD19 CAR-T therapy (NCT02965092). The study aims to evaluate the safety and efficacy of consolidative allo-HSCT following CAR-T therapy in patients with relapsed or refractory B cell Malignancies.

Description:

Anti-CD19 CAR-T therapy has been confirmed effective for relapsed/refractory B-cell malignancies. However, its ability to keep patients in maintained remission is limited. In order to keep patients in long-term remissions, patients who had achieved MRD-negative complete remissions through CAR-T therapy (NCT02965092) will, on their own accord, receive allo-HSCT if there are no previous HSCT, contraindications, and other restrictions.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• 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 malignancies, and has achieved MRD-negative CR through CAR-T therapy (NCT02965092);

2. 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);

3. < 70 years old;

4. Expected survival time > 6 months;

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

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

Exclusion Criteria:

1. With a history of epilepsy or other central nervous system diseases;

2. Previous allogeneic hematopoietic stem cell transplantation;

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. 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);

9. Patients suffering from other uncontrolled diseases, and researchers believe that the patient is not suitable for trial;

10. Patients with HIV-infection;

11. 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

Procedure:
• Allogeneic hematological stem cell transplantation
Patients receive allogeneic hematological stem cell transplantation after they achieve MRD- CR through CAR-T therapy.

Locations

Country	Name	City	State
China	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, People Hospital Of Yichang, Wuhan Union Hospital, China, Xiangyang Central Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events	To evaluate the safety of anti-CD19 CAR-T therapy bridging to allo-HSCT. Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0)	5 years
Secondary	Overall survival	OS was calculated from the date of inclusion to death or last follow-up (censored).	5 years
Secondary	Event-free survival	EFS was calculated from the date of inclusion to death, progression of the disease, relapse or gene recurrence, whichever came first, or last visit (censored).	5 years
Secondary	Relapse-free survival	RFS was calculated from the date of inclusion to relapse or last visit (censored).	5 years