B Cell LeukemiaPhase 1/2NCT03398967
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
A Phase 1/2 study testing Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells in people with B Cell Leukemia and B Cell Lymphoma, run by Chinese PLA General Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 70 years
- Conditions the study is for
- B Cell Leukemia, B Cell Lymphoma
- What is being tested?
- Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 2 Jan 2018to 20 May 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female participant
- 12 Years to 70 Years (Child, Adult, Senior)
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Weidong Han, Dr., 86-10-13651392893, hanwdrsw@sina.com
Daihong Liu, Dr., 86-10-55499136, daihongrm@163.com
About this study
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
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.
Read the detailed description
- PRIMARY OBJECTIVES:
- 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.
- 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.
- SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-tumor response due to universal dual specificity CD19 and CD20 or CD22 CAR-T cell infusions.
- 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.
- Conditions
- B Cell Leukemia, B Cell Lymphoma
- Being tested
- Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells
- Medical subject headings
- Leukemia, B-Cell, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Universal Dual Specificity CD19 and CD20 or CD22 CAR-T CellsBiological
- Biological: Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells
- 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
- Other: Laboratory Biomarker Analysis
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
Measured: 24 weeks
MTD of universal dual specificity CD19 and CD20 or CD22 CAR-T cells
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
Measured: 4 weeks
Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes
Measured: 24 weeks
Secondary outcomes (3)
Six-month Objective response rate of complete remission and partial remission
Measured: 24 weeks
Six-month Overall survival
Measured: 24 weeks
Six-month Progression free survival
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2018
- Study start2 Jan 2018
- Primary completion20 May 2022 (estimated)
- Study completion20 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B Cell LeukemiaStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03398967
- Sponsor's protocol ID
- CHN-PLAGH-BT-026
- Status last verified
- Jan 2018
- First submitted
- 8 Jan 2018
- Last updated
- 16 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03398967
- Acronym / sponsor ID
- CHN-PLAGH-BT-026
- Conditions
- B Cell Leukemia, B Cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 2 Jan 2018 (actual)
- Primary completion
- 20 May 2022 (estimated)
- Study completion
- 20 May 2022 (estimated)
- First posted
- 16 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- PRIMARY OBJECTIVES:
- 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.
- 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.
- SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-tumor response due to universal dual specificity CD19 and CD20 or CD22 CAR-T cell infusions.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 12 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female participant
- 12 Years to 70 Years (Child, Adult, Senior)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells1. 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 | Biological | – |
Primary outcome
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
3 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells in people with B Cell Leukemia and B Cell Lymphoma, run by Chinese PLA General Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wenying Zhang (86-10-55499341, zhangwenying.1984@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability (time frame: 24 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2018.