Clinical trial NCT03366350: Anti-CD19 CAR-T Therapy Bridging to HSCT for CD19+ B-Cell Malignancies
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Acute Lymphoblastic Leukemia
B Cell Lymphoma
Lead sponsor: Wuhan Sian Medical Technology Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Wuhan Union Hospital, China
name: Jingzhou Central Hospital
name: Xiangyang Central Hospital
name: People Hospital Of Yichang
First posted: 2017-12-08
Enrollment: 50
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients receive consolidative allo-HSCT following CAR-T therapy.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
measure: Event-free survival
timeFrame: 5 years
measure: Relapse-free survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: YU HU, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: