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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

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.

Condition or disease Intervention/treatment Phase
B Cell Leukemia B Cell Lymphoma Biological: Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 2, 2018
Estimated Primary Completion Date : May 20, 2022
Estimated Study Completion Date : May 20, 2022



Intervention Details:
  • 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


Primary Outcome Measures :
  1. Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 24 weeks ]
  2. 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

  3. Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. Six-month Objective response rate of complete remission and partial remission [ Time Frame: 24 weeks ]
  2. Six-month Overall survival [ Time Frame: 24 weeks ]
  3. Six-month Progression free survival [ Time Frame: 24 weeks ]


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Ages Eligible for Study:   12 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT03398967


Contacts
Contact: Wenying Zhang 86-10-55499341 zhangwenying.1984@163.com

Locations
China, Beijing
Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital Recruiting
Beijing, Beijing, China, 100853
Contact: Weidong Han, Dr.    86-10-13651392893    hanwdrsw@sina.com   
Contact: Daihong Liu, Dr.    86-10-55499136    daihongrm@163.com   
Principal Investigator: Weidong Han, Dr.         
Principal Investigator: Daihong Liu, Dr.         
Sponsors and Collaborators
Chinese PLA General Hospital

Responsible Party: Han weidong, Director of Molecular & Immunological Department, Biotherapeutic Department, Chinese PLA General Hospital
ClinicalTrials.gov Identifier: NCT03398967     History of Changes
Other Study ID Numbers: CHN-PLAGH-BT-026
First Posted: January 16, 2018    Key Record Dates
Last Update Posted: January 16, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Leukemia
Lymphoma, B-Cell
Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid