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A Clinical Research of CD20-Targeted CAR-T in B Cell Malignancies

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ClinicalTrials.gov Identifier: NCT02710149
Recruitment Status : Recruiting
First Posted : March 16, 2016
Last Update Posted : June 25, 2019
Sponsor:
Information provided by (Responsible Party):
Shiqi Li, Southwest Hospital, China

Brief Summary:
The main purpose of this study is to explore the therapeutic effect of CD20-targeted chimeric antigen receptor T(CAR-T) cells in the treatment of B cell malignancies.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Biological: Anti-CD20-CAR-transduced T cells Phase 1 Phase 2

Detailed Description:
The anti-CD20 antibody has been broadly used in the treatment of B cell malignancies and exhibited good clinical outcomes. The CD19-targeted CAR-T has shown exellent therapeutic efficiency in B cell malignancies,especially in acute lymphocytic leukemia. However, patients treated with CD19-targeted CAR-T may face relapse of CD19 mutation. Other targets aimed CAR-T is in need. Therefore we constructed CD20-targeted CAR-T cells and hope to start a clinicaltrial to explore the therapeutic effect of CD20-targeted CAR-T cells in the treatment of B cell malignancies.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Research of CD20-Targeted CAR-T in B Cell Malignancies
Study Start Date : March 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: B Cell Malignancies
The trial will be conducted in a manner of simon two-stage design with Anti-CD20-CAR-transduced T cells, beginning in the first stage with the aim of over 30% reaction rate among 15 patients with B cell malignancies. Only when the expected reaction rate is achieved the 30 patients left can be recruited.
Biological: Anti-CD20-CAR-transduced T cells
Patients receive autologous-derived CD20-targeted CAR-T cells on day 1, 2 after receiving lymphodepleting chemotherapy.
Other Name: CD20-targeted CAR-T cells




Primary Outcome Measures :
  1. Adverse Events That Are Related to Treatment [ Time Frame: 2 years ]
    Determine the toxicity profile of the CD20 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.


Secondary Outcome Measures :
  1. In vivo existence of Anti-CD20 CAR-T cells [ Time Frame: 2 years ]
  2. Reaction Rate of Treatment [ Time Frame: 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. CD20-expressing B cell malignancy must be assured and must be relapsed or refractory disease after at least one standard chemotherapy and one salvage regimen. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.
  2. Patients enrolled must have an evaluated score above 60 with KPS.
  3. CD20 expression of the malignant cells must be detected by immunohistochemistry or by flow cytometry. In general immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.
  4. Gender is not limited, age from 14 years to 75 years.
  5. Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
  6. Patients are expected to survive for more than 3 months by their physicians at the time of enrollment.
  7. Adequate absolute CD3 count estimated need to be assured for obtaining target cell dose based on dosage cohorts.
  8. Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:

    CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs; CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation)

  9. Patients with isolated CNS relapse will be eligible if they have previously been treated with cranial radiation (at least 1800 cGy).
  10. Ability to give informed consent.
  11. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
  12. Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.
  13. Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L.
  14. Patients with history of allogeneic stem cell transplantation are eligible if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
  15. Patients volunteer to participate in the research.

Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for participation in the study:

  1. Patients are evaluated below 60 scores with KPS.
  2. Evident signs suggesting that patients are potentially allergic to cytokines.
  3. Frequent infection history and recent infection is uncontrolled.
  4. Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
  5. Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
  6. Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
  7. Pregnancy and nursing females.
  8. HIV infection.
  9. Active hepatitis B or active hepatitis C.
  10. Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.
  11. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
  12. Patients with a known history or prior diagnosis of other serious immunologic, malignant or inflammatory disease.
  13. Other situations we think not eligible for participation in the research.

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): NCT02710149


Contacts
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Contact: Cheng Qian, MD, PhD 0086-023-68765461 cqian3184@163.com
Contact: Zhi Yang, PhD 0086-13206140093 Lystch@qq.com

Locations
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China, Chongqing
Southwest Hospital of Third Millitary Medical University Recruiting
Chongqing, Chongqing, China, 400000
Contact: Cheng Qian, PhD    008615086883400    cqian3184@163.com   
Contact: Zhi Yang, PhD    008613206140093      
Principal Investigator: Cheng Qian, PhD         
Sponsors and Collaborators
Southwest Hospital, China
Investigators
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Study Chair: Cheng Qian, MD, PhD Biotherapy Center of Southwest Hospital
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Responsible Party: Shiqi Li, Researcher of Biotherapy Center, Southwest Hospital, China
ClinicalTrials.gov Identifier: NCT02710149    
Other Study ID Numbers: TMMU-BTC-003
First Posted: March 16, 2016    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Shiqi Li, Southwest Hospital, China:
CAR-T
Leukemia
Lymphoma
Additional relevant MeSH terms:
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Leukemia
Neoplasms by Histologic Type
Neoplasms