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Trial record 1 of 1 for:    03840317
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Senl_1904A and Senl_1904B Chimeric Antigen Receptor (CAR) T-Cell in the Treatment of r/ r Acute B Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT03840317
Recruitment Status : Active, not recruiting
First Posted : February 15, 2019
Last Update Posted : January 20, 2021
Sponsor:
Collaborator:
Hebei Yanda Ludaopei Hospital
Information provided by (Responsible Party):
Hebei Senlang Biotechnology Inc., Ltd.

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.

Condition or disease Intervention/treatment Phase
Acute Lymphocytic Leukemia Biological: Autologous CD19-targeting CAR T cells Phase 1

Detailed Description:
The CARs consist of an anti-CD19 single-chain variable fragment(scFv) that was derived from the FMC63 mouse hybridoma, a portion of the human CD137(4-1BB) molecule, and the intracellular component of the human CD3ζ molecule. Autologous T cells will be gene engineered with the CAR gene using a lentivirus vector. Compared to Senl_1904A, Senl_1904B has a higher and more stable transfection efficiency and secretes lower levels of cytokines in functional assays, thus having the potential to significantly reduce the incidence of serious adverse events while ensuring the same complete response rate. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After T cell infusion, the patients will be evaluated for one month after infusion for adverse reactions and efficacy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Parallel-arm, Controlled Trial of Senl_1904A and Senl_1904B Autologous CAR-T Cell Injections in the Treatment of Relapsed and Refractory Acute B Lymphocytic Leukemia(r/r B-ALL)
Actual Study Start Date : January 2, 2019
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : January 31, 2022


Arm Intervention/treatment
Experimental: Senl_1904A CD19 CAR-T
Autologous CD19-targeting CAR T cells, dosage 3*10^5/kg, intravenous injection once
Biological: Autologous CD19-targeting CAR T cells
Autologous CD19-targeting CAR T cells

Experimental: Senl_1904B CD19 CAR-T
Autologous CD19-targeting CAR T cells,dosage 3*10^5/kg, intravenous injection once
Biological: Autologous CD19-targeting CAR T cells
Autologous CD19-targeting CAR T cells




Primary Outcome Measures :
  1. Tumor load [ Time Frame: up to one month ]
    Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.


Secondary Outcome Measures :
  1. CAR T cell expansion [ Time Frame: up to one month ]
    The percentage of CAR-T cells (CAR+/CD3+ T cells) in the bone marrow samples, quantified by flow cytometry.

  2. CAR T cell persistence [ Time Frame: up to one month ]
    The method to detect CAR-T cell persistence is by determining the exact copies of CAR per ug DNA in BM through quantitative polymerase chain reaction(qPCR)



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with acute lymphocytic leukemia who voluntarily signed informed consent and met the following criteria:

    1. Patients with relapsed and refractory acute B lymphocytic leukemia with any of the following:

      1. 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 );
      2. Primary B-ALL patients who cannot be completely relieved by repeated chemotherapy twice or more;
      3. High-risk initial onset B-ALL patients not completely relieved after 1 or 2 times of chemotherapy but not suitable for re-chemotherapy ;
    2. Tumor cells confirmed CD19 positive by Flow cytometry (FCM)
    3. For B-ALL patients with simple extramedullary recurrence , there must be at least one evaluable lesion;
    4. Eastern Cooperative Oncology Group (ECOG) ≤ 2 points;
    5. Age 3 - 65 years old;
    6. The bone marrow tumor load value (morphology) > 5% at the time of enrollment;
    7. 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;
    8. The expected survival time is longer than 3 months;
    9. 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
    10. An informed consent form is required.

Exclusion Criteria:

  • 1) 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:

  1. The subjects request to withdraw from the study before CAR-T infusion
  2. The subjects seriously violate the protocol
  3. 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;

  4. 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 ;
  5. Not enough T cells for manufacture standard CAR-T cells
  6. Other serious adverse events occurred
  7. MRD become negative after preconditioning regiment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03840317


Locations
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China, Hebei
Hebei Yanda Ludaopei Hospital
Langfang, Hebei, China, 065000
Sponsors and Collaborators
Hebei Senlang Biotechnology Inc., Ltd.
Hebei Yanda Ludaopei Hospital
Investigators
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Principal Investigator: Peihua Lu, PhD&MD Hebei Yanda Ludaopei Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hebei Senlang Biotechnology Inc., Ltd.
ClinicalTrials.gov Identifier: NCT03840317    
Other Study ID Numbers: Senl_1904A & Senl_1904B CAR-T
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases