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A Feasibility and Safety Study of Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cell Immunotherapy for Relapsed or Refractory Leukemia and Lymphoma

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ClinicalTrials.gov Identifier: NCT03398967
Recruitment Status : Recruiting
First Posted : January 16, 2018
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
Han weidong, Chinese PLA General Hospital

Tracking Information
First Submitted Date  ICMJE January 8, 2018
First Posted Date  ICMJE January 16, 2018
Last Update Posted Date January 16, 2018
Actual Study Start Date  ICMJE January 2, 2018
Estimated Primary Completion Date May 20, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 24 weeks ]
  • MTD of universal dual specificity CD19 and CD20 or CD22 CAR-T cells [ Time Frame: 4 weeks ]
    The highest dose of universal dual specificity CD19 and CD20 or CD22 CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of universal dual s
  • Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes [ Time Frame: 24 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Six-month Objective response rate of complete remission and partial remission [ Time Frame: 24 weeks ]
  • Six-month Overall survival [ Time Frame: 24 weeks ]
  • Six-month Progression free survival [ Time Frame: 24 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Feasibility and Safety Study of Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cell Immunotherapy for Relapsed or Refractory Leukemia and Lymphoma
Official Title  ICMJE Phase I/II Study to Evaluate Treatment of Relapsed or Refractory Leukemia and Lymphoma With Universal CRISPR-Cas9 Gene-Editing CAR-T Cells Targeting CD19 and CD20 or CD22
Brief Summary CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. Dual Specificity CD19 and CD20 or CD22 CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD20 or CD22. This is a phase 1/2 study designed to determine the safety of the allogenic gene-edited dual specificity CD19 and CD20 or CD22 CAR-T cells and the feasibility of making enough to treat patients with relapsed or refractory hematological malignancies.
Detailed Description
  1. PRIMARY OBJECTIVES:

    1. To evaluate the feasibility and safety of universal dual specificity CD19 and CD20 or CD22 CAR-T cells in patients with relapsed or refractory leukemia and lymphoma.
    2. To evaluate the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells. Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to detect and quantify survival of universal dual specificity CD19 and CD20 or CD22 CAR-T cells over time.
  2. SECONDARY OBJECTIVES:

    1. For patients with detectable disease, measure anti-tumor response due to universal dual specificity CD19 and CD20 or CD22 CAR-T cell infusions.
    2. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable universal dual specificity CD19 and CD20 or CD22 CAR-T cells (loss of engraftment).

The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using a "split dose" approach to dosing: 10% on day 0, 30% on day 1 and 60% on day 2.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • B Cell Leukemia
  • B Cell Lymphoma
Intervention  ICMJE Biological: Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells
  1. Biological: Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells
  2. Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose. D2: 60% of total dose if patient is stable (no significant toxicity) from prior dose
  3. Other: Laboratory Biomarker Analysis
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 8, 2018)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 20, 2022
Estimated Primary Completion Date May 20, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participant
  2. 12 Years to 70 Years (Child, Adult, Senior)
  3. Patient with relapsed or refractory B-cell leukemia or lymphoma
  4. Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
  5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  6. Adequate organ function

Exclusion Criteria:

  1. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
  2. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
  3. Richter's syndrome
  4. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
  5. Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
  6. Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
  7. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
  8. Patient has an investigational medicinal product within the last 30 days prior to screening
  9. Previous treatment with investigational gene or cell therapy medicine products
  10. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
  11. Pregnant or nursing women
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Wenying Zhang 86-10-55499341 zhangwenying.1984@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03398967
Other Study ID Numbers  ICMJE CHN-PLAGH-BT-026
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Han weidong, Chinese PLA General Hospital
Study Sponsor  ICMJE Chinese PLA General Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Chinese PLA General Hospital
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP