Clinical trial NCT03366324: Anti-CD19 CAR-T Therapy Combine With HSCT to Treat MRD+ B-cell Malignancies
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
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: The First People's Hospital of Yuhang District
First posted: 2017-12-08
Enrollment: 20
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: The only one group of patients will receive the combination of CAR-T therapy and HSCT.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of study related adverse events
timeFrame: 200 days from enrollment
Secondary outcomes:
measure: Number of participants with an MRD negative complete remission after CAR-T therapy and HSCT
timeFrame: 2 years from enrollment
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
name: YU HU, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: