Back to resultsA Feasibility and Safety Study of Concomitant Therapy With Allo-CAR-T Cells and Allo-HSCT in Patients With Relapse or Refractory Leukemia
Primary Purpose
B Cell Leukemia
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells; donor-derived-HSCT
Sponsored by
About this trial
This is an interventional treatment trial for B Cell Leukemia
Eligibility Criteria
Inclusion Criteria:
- Male or female participant
- 12 Years to 60 Years
- Patient with relapsed or refractory B-cell leukemia or lymphoma
- Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Adequate organ function
Exclusion Criteria:
- Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
- Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
- Richter's syndrome
- Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
- Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
- Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
- Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
- Patient has an investigational medicinal product within the last 30 days prior to screening
- Previous treatment with investigational gene or cell therapy medicine products
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- Pregnant or nursing women
Sites / Locations
- Biotherapeutic Department and Hematology Department of Chinese PLA General HospitalRecruiting
Outcomes
Primary Outcome Measures
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
Secondary Outcome Measures
Overall remission rate (ORR) = CR + CRi
Six-month Overall survival
Six-month Progression free survival
Full Information
NCT ID
NCT03463928
First Posted
March 7, 2018
Last Updated
March 12, 2018
Sponsor
Chinese PLA General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03463928
Brief Title
A Feasibility and Safety Study of Concomitant Therapy With Allo-CAR-T Cells and Allo-HSCT in Patients With Relapse or Refractory Leukemia
Official Title
Phase I Study to Evaluate Treatment of Relapsed or Refractory Leukemia With Donor-derived HSCT Following Donor-derived CD19/22 Bispecific CAR-T Cells or CD19-directed CAR-T Cells
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Unknown status
Study Start Date
October 8, 2017 (Actual)
Primary Completion Date
June 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Allogenic hematopoietic stem cell transplant (Allo-HSCT) is routinely used for treatment of aggressive hematological malignancies. The biological foundation of allo-HSCT is the graft-versus-leukemia (GVL) effect, which is primarily mediated by donor T cells present in the graft and is able to eradicate malignant B cells either CD19+ or CD19-. Relapse following an allo-HSCT remains a major challenge in the treatment of B-ALL. 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. Co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT has the potential to combine the CAR-T cell mediated targeted elimination of CD19 expressing B cells with GVL effect, which could have clear advantages in reducing the risk of relapse and the evolution of CD19- escape variants or clonally related malignancies in other lineages. Therefore, a complete and durable tumor responses induced by this immunotherapy could be expected.
Detailed Description
PRIMARY OBJECTIVES:
To evaluate the feasibility and safety of donor-derived HSCT following donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells in patients with relapsed or refractory leukemia.
To evaluate the duration of in vivo persistence of adoptively transferred CAR-T cells, and the phenotype of persisting T cells. Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM will be used to detect and quantify survival of infused allo-CAR-T cells over time.
To evaluate the donor chimerism after co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT
SECONDARY OBJECTIVES:
For patients with detectable disease, measure anti-tumor response due to co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT.
The allo-CAR-T cells will be infused in a fractionated manner, 1/3 on day 0, 2/3 on day 1.The allo-HSCT will be infused on day 2.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B Cell Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells; donor-derived-HSCT
Intervention Description
The allo-CAR-T cells will be infused in a fractionated manner, 1/3 on day 0, 2/3 on day 1.The allo-HSCT will be infused on day 2.
Primary Outcome Measure Information:
Title
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Overall remission rate (ORR) = CR + CRi
Time Frame
24 weeks
Title
Six-month Overall survival
Time Frame
24 weeks
Title
Six-month Progression free survival
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female participant
12 Years to 60 Years
Patient with relapsed or refractory B-cell leukemia or lymphoma
Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Adequate organ function
Exclusion Criteria:
Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
Richter's syndrome
Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
Patient has an investigational medicinal product within the last 30 days prior to screening
Previous treatment with investigational gene or cell therapy medicine products
Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
Pregnant or nursing women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hejin Jia
Phone
86-10-55499341
Email
jiahejin@163.com
Facility Information:
Facility Name
Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital
City
Beijing
ZIP/Postal Code
100853
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weidong Han
Phone
86-10-13651392893
Email
hanwdrsw@sina.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Feasibility and Safety Study of Concomitant Therapy With Allo-CAR-T Cells and Allo-HSCT in Patients With Relapse or Refractory Leukemia
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