Senl_1904A and Senl_1904B Chimeric Antigen Receptor （CAR） T-Cell in the Treatment of r/ r Acute B Lymphocytic Leukemia

NCT03840317 | Unknown Phase 1

• 1 other identifier: Senl_1904A & Senl_1904B CAR-T
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open, two arms, mask phase I clinical study to evaluate efficacy and safety of two different chimeric antigen receptor T cell immunotherapies (Senl\_1904A and Senl\_1904B) targeting cluster of differentiation antigen 19 （CD19） in the treatment of Acute lymphocytic Leukemia. A total of 20 patients are planned to be enrolled following up half a year.

Conditions

Acute Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Tumor load

  Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.

  up to one month

Secondary Outcomes (2)

• CAR T cell expansion

  up to one month

• CAR T cell persistence

  up to one month

Study Arms (2)

Senl_1904A CD19 CAR-T

EXPERIMENTAL

Autologous CD19-targeting CAR T cells, dosage 3\*10\^5/kg, intravenous injection once

Biological: Autologous CD19-targeting CAR T cells

Senl_1904B CD19 CAR-T

EXPERIMENTAL

Autologous CD19-targeting CAR T cells,dosage 3\*10\^5/kg, intravenous injection once

Biological: Autologous CD19-targeting CAR T cells

Interventions

Autologous CD19-targeting CAR T cells BIOLOGICAL

Autologous CD19-targeting CAR T cells

Senl_1904A CD19 CAR-T; Senl_1904B CD19 CAR-T

Eligibility Criteria

• Age: 3 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with acute lymphocytic leukemia who voluntarily signed informed consent and met the following criteria:
• Patients with relapsed and refractory acute B lymphocytic leukemia with any of the following:
• Recurrence after remission by chemotherapy or autologous stem cell transplantation (including B-ALL patients with bone marrow recurrence of morphology and recurrence of micro-residual );
• Primary B-ALL patients who cannot be completely relieved by repeated chemotherapy twice or more;
• High-risk initial onset B-ALL patients not completely relieved after 1 or 2 times of chemotherapy but not suitable for re-chemotherapy ;
• Tumor cells confirmed CD19 positive by Flow cytometry (FCM)
• For B-ALL patients with simple extramedullary recurrence , there must be at least one evaluable lesion;
• Eastern Cooperative Oncology Group (ECOG) ≤ 2 points;
• Age 3 - 65 years old;
• The bone marrow tumor load value (morphology) \> 5% at the time of enrollment;
• The main organ function needs to meet the above conditions: cardiac ultrasound or multiple gated image acquisition analysis （MUGA） scan indicate the cardiac ejection fraction is ≥50% , and there is no obvious abnormality in the electrocardiogram; blood oxygen saturation≥90%; creatinine ≤1.6mg/dl; alanine amino transferase (ALT) and Aspartate transaminase (AST)≤3 times normal range, total bilirubin（TBil） ≤2.0mg/dl;
• The expected survival time is longer than 3 months;
• The pregnancy test for women of childbearing age must be negative; Subjects with a pregnancy plan must agree to take contraception before the enrollment study and after the study lasts for one year; if the subject is pregnant or suspects of pregnancy, the investigator should be notified immediately
• An informed consent form is required.

You may not qualify if:

• \) Severe cardiac insufficiency; 2) A history of severe pulmonary dysfunction; 3) Combined with other malignant tumors; 4) Combined with serious infections or persistent infection and cannot be effectively controlled; 5) Combined with metabolic diseases (except DM); 6) Combined with severe autoimmune diseases or congenital immune defects; 7) Active hepatitis (HBV DNA or HCVRNA detection positive); 8) HIV infection or syphilis infection; 9) A history of severe allergies to biological products (including antibiotics); 10) Subjects with recurrence after allogeneic hematopoietic stem cell transplantation 11) chronic lymphocytic leukemia（CLL） /myeloproliferative neoplasms with acute lymphoid transformation or CLL transform to ALL ; 12) Any drug that has been used against graft-versus-host disease（GVHD） for nearly 4 weeks, such as methotrexate or other chemotherapeutic drugs, mycophenolate mofetil, immunosuppressive antibodies, etc.; 13) Subjects who have received any anti-CD19 medication; 14) Subjects who have used anti-cluster of differentiation antigen 20（CD20） drugs (such as rituximab) for nearly 4 weeks; 15) Subjects who have participated in any other clinical drug trials in the past six months; 16) Female patients who are pregnant and lactating, or have a pregnancy plan within 12 months; 17) The investigator believes that it may increase the risk of the subject or interfere with the outcome of the test (with a history of severe mental illness, drug abuse and history of addiction).
• Exit criteria：
• The subjects request to withdraw from the study before CAR-T infusion
• The subjects seriously violate the protocol
• Before CAR-T infusion, the following indicators are still abnormal after treatment:
• Platelets \<20x10\^9/L, hemoglobin ≤80g/L, peripheral finger oxygen \<90%, AST / ALT / alkaline phosphatase（ALP） ≥ 2.5 upper limits of normal（ULN）, total bilirubin ≥ 1.5ULN , creatinine clearance rate \<70ml / min, left ventricular ejection fraction \<50%, the researcher judged that the test needs to be terminated early;
• The therapeutic dose of steroids was not stopped within 72 hours prior to CAR-T infusion and the investigator determined that the trial needs to be terminated . However, the following physiologically acceptable doses of steroids are permissible: hydrocortisone or equivalent \<6-12 mg/m2/day ;
• Not enough T cells for manufacture standard CAR-T cells
• Other serious adverse events occurred
• MRD become negative after preconditioning regiment

Sponsors & Collaborators

• Hebei Senlang Biotechnology Inc., Ltd.: lead
• Hebei Yanda Ludaopei Hospital: collaborator

Study Sites (1)

Hebei Yanda Ludaopei Hospital

Langfang, Hebei, 065000, China

Location

Related Publications (1)

• Ho JY, Wang L, Liu Y, Ba M, Yang J, Zhang X, Chen D, Lu P, Li J. Promoter usage regulating the surface density of CAR molecules may modulate the kinetics of CAR-T cells in vivo. Mol Ther Methods Clin Dev. 2021 Mar 13;21:237-246. doi: 10.1016/j.omtm.2021.03.007. eCollection 2021 Jun 11.

  PMID: 33869653 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Peihua Lu, PhD&MD

  Hebei Yanda Ludaopei Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2019
• First Posted: February 15, 2019
• Study Start: January 2, 2019
• Primary Completion: September 1, 2021
• Study Completion: January 31, 2022
• Last Updated: January 20, 2021

Record last verified: 2021-01

Locations

CN (1)