Clinical trial NCT03902197: CD19 hsCAR-T for Refractory/Relapsed CD19+ B-ALL Patients
Official title: A Phase II Study of CD19 hsCAR-T for Refractory/Relapsed CD19+ B-ALL Patients Previously Treated With Cell Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Keywords: CD19 hsCAR-T
B-ALL
Humanized selective CAR
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Beijing Children's Hospital
First posted: 2019-04-03
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This Phase II study is to evaluate the efficacy and safety of a CD19-targeting humanized selective CAR-T (CD19 hsCAR-T) in refractory/relapsed CD19+ B-ALL leukemia patients who have no available curative treatment options, have a limited prognosis with currently available treatments, and were previously treated with a B cell directed cell therapy.

Detailed description: CD19+ B-ALL patients who have relapsed after murine-based CD19 CAR-T (CD19mCAR-T) treatment and/or have limited clinical response to CD19mCAR-T will be enrolled to receive CD19 hsCAR-T treatment.

Eligibility criteria: Inclusion Criteria:

1. Subjects with refractory/relapse B-cell ALL with no available curative treatment options (such as autologous or allogeneic SCT);
2. Subjects previously treated with B cell-directed engineered cell therapy are eligible if they meet the following criteria:

   1. relapsed and/or MRD-positive after prior cell therapy;
   2. partial response to prior cell therapy;
   3. Clinical and laboratory data are available;
3. Documented CD19 expression after previous B cell-directed therapies;
4. Aged 1 to 75 years;
5. KPS\>40；
6. At least 2 weeks or 5 drug half-lives, whichever is shorter must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy;
7. Women of childbearing potential must have a urine pregnancy test taken and proven negative prior to the treatment. All patients agree to use reliable methods of contraception during the trial period and throughout the last follow-up visit;
8. Subjects with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if the patients do not present with active GVHD and are not undergoing immunosuppressive regimes;
9. Patients with CNS3 (WCB ≥5/mL in CSF with presence of lymphoblasts) disease will be eligible if the CNS disease is responsive to therapy;
10. Participation in the clinical trials should be voluntary with signed informed consent.

Exclusion Criteria:

1. Patients with hypervolemia (white blood cell count\> 50 x 10\^9 / L) or rapidly progressive disease that in the estimation of the investigators and sponsors would compromise the patient's ability to complete the study;
2. History of melanoma skin cancer or other primary tumors (eg, cervical cancer, bladder cancer, breast cancer) (except for those with 3 years or longer of cure);
3. Patients with fungal, bacterial, viral, or other uncontrollable infections or infections requiring Level 4 isolation (UTI or inoculation assays may be performed if necessary);
4. Patients with positive results for HIV, HBV, HCV tests;
5. With CNS disorders such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement;
6. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac diseases within 12 months of enrollment, or with cardiac atrial or cardiac ventricular lymphoma;
7. Patients that are receiving anticoagulant therapy or have ever coagulation disorders;
8. Any medical condition that in the judgment of the sponsors/investigators is likely to interfere with assessment of safety or efficacy of study;
9. History of severe immediate hypersensitivity reaction to any of the agents used in this study;
10. Female patients who are pregnant or breastfeeding;
11. Feasibility assessment during screening demonstrates \<30% transduction of target lymphocytes, or insufficient expansion (\< 5-fold) in response to CD3/CD28 co-stimulation;
12. Patients with any uncontrolled diseases that are unsuitable for enrollment;
13. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity;
14. Any situation that is considered to potentially increase the risk of the subject or interfere with the outcome of the study;
15. Patients who have been enrolled in other clinical studies.

Primary outcomes:
measure: Overall response rate (ORR) within 3 months
timeFrame: 3 months
Secondary outcomes:
measure: Best overall response (BOR)
timeFrame: 3 months
measure: Duration of remission (DoR)
timeFrame: 1 year
measure: Event free survival within 1 year
timeFrame: 1 year
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])
timeFrame: 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Children's Hospital Capital Meidcal University
state: Beijing
city: Beijing
country: China
facility: Beijing Children's Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Zhiguo Chen, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Children's Hospital
name: Huyong Zheng, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: