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

Phase 1

• Conditions: B Cell Lymphoma; Acute Lymphoblastic Leukemia
• Interventions: Procedure: Allogeneic hematological stem cell transplantation

• Registration Number: NCT03366350
• Lead Sponsor: Wuhan Sian Medical Technology Co., Ltd

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2016-04-15
• Study First Submitted: 2017-12-01
• Study First Submitted QC: 2017-12-07
• Study First Posted: 2017-12-08
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-08
• Last Update Posted: 2019-05-10
• Primary Completion: 2021-01-01
• Study Completion: 2021-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Consolidative allo-HSCT following CAR-T therapy	Allogeneic hematological stem cell transplantation	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.

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events	5 years	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)

Secondary Outcome Measures

Name	Time	Method
Overall survival	5 years	OS was calculated from the date of inclusion to death or last follow-up (censored).
Relapse-free survival	5 years	RFS was calculated from the date of inclusion to relapse or last visit (censored).
Event-free survival	5 years	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).

Trial Locations

Locations (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China