Clinical trial NCT03344705: Safety and Efficacy Evaluation of IM19 Cells
Official title: Safety and Efficacy Evaluation of IM19 Chimeric Antigen Receptor-modified T Cells (IM19CAR-T) In CD19+ B Cell Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hematological Malignancies
Lead sponsor: Beijing Immunochina Medical Science & Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-11-17
Enrollment: 20
Sex: ALL
Minimum age (years): 4
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: Assessment of the Safety and Feasibility of Administering T cells Expressing an Anti-CD19 Chimeric Antigen Receptor to Patients With CD19+ B-cell Hematological Malignancies.

Detailed description: Assessment of the Safety and Feasibility of Administering T cells Expressing an Anti-CD19 Chimeric Antigen Receptor to Patients With CD19+ B-cell Hematological Malignancies(including B-cell Acute lymphoblastic Leukemia、B-cell Chronic Lymphocytic Leukemia、Non-Hodgkin's lymphoma) and Determine the Best Dosage.

Eligibility criteria: Inclusion Criteria:

1. Patients with CD19 positive relapsed or refractory B-cell malignancies, including B-cell Acute Lymphocytic Leukemia(ALL)、B-cell Chronic Lymphocytic Leukemia(CLL)、Non-Hodgkin's lymphoma(NHL).

1)Patients with ALL:

* Previously treated with at least two courses of chemotherapy Ⅱ The interval of the last chemotherapy and disease progression is less than one year.

  Ⅲ Not suitable for allogeneic stem cell transplantation. 2)Patients with CLL:
* Previously treated with at least two courses of chemotherapy

  Ⅱ The interval of the last chemotherapy and disease progression is less than two years.

  Ⅲ Not suitable for allogeneic stem cell transplantation conditions or due to conditions to abandon allogeneic stem cell transplantation.

  3) Patients with DLBCL or FL、PMBCL:
* Patients who relapsed or were refractory after at least two previous treatments.

  Ⅱ Patients who relapsed after transplantation. 4)Patients who have relapsed or have refractory mantle cell lymphoma after at least one treatment.

  2.Measurable disease,including minimal residual disease. 3.Gender is not limited, to be aged 4 to 75 years 4.Expected survival \>3 months. 5.Eastern Cooperative Oncology Group(ECOG) score 0-2. 6.Women of childbearing potential must have a blood pregnancy test taken and proven negative prior to the treatment. All patients agree to use reliable methods of contraception during the trial period and until follow-up for the last time.

  7.Absence of symptoms of central nervous system(CNS) leukemia.

Exclusion Criteria:

1. Patients who have been treated with chemotherapy or radiotherapy within 2 weeks before blood collection.
2. Patients have GVHD, which needs treatment with immunosuppressive agents,or patients with autoimmune diseases.
3. Patient who have been treated with systemic steroid medication within two weeks of blood collection（Except for the recent or current use of inhaled steroids）.
4. Patient who have been treated with stimulation of bone marrow hematopoietic cells generated drugs(Such as Recombinant Human Granulocyte Colony-stimulating Factor Injection) within 2 weeks before the blood collection period to use .
5. The number of T cells in peripheral blood is lower than 2×10\^8/L.
6. Previously treatment with any gene therapy products.
7. History of epilepsy or other CNS disease.
8. New York Heart Association(NYHA) grade≥Ⅲ.
9. Creatinine\> 1.5×normal value，Alanine transaminase(ALT) /Aspartate aminotransferase(AST)\>3×normal value，Bilirubin \>2×normal value.
10. Degree of myeloproliferation： Ⅳ-V
11. Active hepatitis B , hepatitis C or HIV infection and cytomegalovirus infection ,Epstein-Barr virus infection or any other uncontrolled active infection.
12. Pregnancy or breast-feeding women.
13. Any uncontrolled medical disorders that the researchers considered are not suitable to participate the clinical trial.
14. Any situation that would increase dangerousness of subjects or disturb the outcome of the clinical study according to the researcher's evaluation.

Primary outcomes:
measure: Occurrence of study related adverse events
timeFrame: 2 years
Secondary outcomes:
measure: Overall response rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
Study officials:
affiliation: Peking University Third Hospital
name: Hongmei Jing, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bao F, Wan W, He T, Qi F, Liu G, Hu K, Lu XA, Yang P, Dong F, Wang J, Jing H. Autologous CD19-directed chimeric antigen receptor-T cell is an effective and safe treatment to refractory or relapsed diffuse large B-cell lymphoma. Cancer Gene Ther. 2019 Jul;26(7-8):248-255. doi: 10.1038/s41417-018-0073-7. Epub 2019 Jan 9.