CD19 hsCAR-T for Refractory/Relapsed CD19+ B-ALL Patients

NCT ID: NCT03902197

Last Updated: 2019-04-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-22
• Study Completion Date: 2023-12-21

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.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CD19 hsCAR-T

This cohort will be administrated by T cells transduced with lentivirus vectors expressing CD19 hsCAR

Group Type: EXPERIMENTAL

CD19 hsCAR-T

Intervention Type: BIOLOGICAL

CD19 hsCAR-T will be administered by I.V. infusion

Interventions

CD19 hsCAR-T

CD19 hsCAR-T will be administered by I.V. infusion

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Children's Hospital

OTHER

Sponsor Role: collaborator

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhiguo Chen, PhD

Role: PRINCIPAL_INVESTIGATOR

Xuanwu Hospital, Beijing

Huyong Zheng, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Beijing Children's Hospital

Locations

Beijing Children's Hospital Capital Meidcal University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Beijing Children's Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhiguo Chen, PhD

Role: CONTACT

chenzhiguo@gmail.com

86-10-83198889

Yu Zhao, PhD

Role: CONTACT

zhaoyu198387@gmail.com

86-10-83198274

Facility Contacts

Huyong Zheng, MD, PhD

Role: primary

Huyong Zheng, MD, PhD

Role: primary

Other Identifiers

CD19hsCAR20190401

Identifier Type: -

Identifier Source: org_study_id