CD19 Positive Malignant B-cell Leukemia and LymphomaPhase 1NCT02933775
CD19-redirected Autologous Cells (CAR-CD19 T Cells)
A Phase 1 study testing CAR-CD19 T cells, Fludarabine and Cyclophosphamide in people with CD19 Positive Malignant B-cell Leukemia and Lymphoma, run by RenJi Hospital at 1 site in China.
Trial summary
This study is designed for determining the safety and relative engraftment levels of the redirected autologous T cells transduced with the anti-CD19 lentiviral vector in patients with CD19-positive B cell leukemia and malignant lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- CD19 Positive Malignant B-cell Leukemia and Lymphoma
- What is being tested?
- CAR-CD19 T cells, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteChina
- Study dates
- Oct 2016to Jan 2020
- Phase
- Phase 1
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with documented CD19-positive malignant B cell leukemia and lymphoma.
- Patients aged between 18 ~ 65 with malignant B cell leukemia and lymphoma.
- CD19-positive B cell leukemia or lymphoma.
- Expected survival > 12 weeks.
- ECOG scores 0-1, or KPS scores > 80.
- Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
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- WBC ≥ 2.5×109/L; LY ≥ 0.7×109/L; LY% ≥ 15%.
- Creatinine ≤ 2.0 mg/dL (176.8 μmol/L).
- ALT/AST ≤ 2.5 ULN.
- Bilirubin ≤ 2.0 mg/dL (34.2 μmol/L).
- Prothrombin Time (PT) : International Normalized Ratio (INR) < 1.7, or PT is at most 4 s longer than normal value.
- All tests results should comply with the above criteria. No continuing supportive care is received.
Who cannot join
- 1. CD19-negative B cell leukemia or lymphoma. 2. Feasibility assessment during screening demonstrates < 5% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to αCD3/CD28 costimulation.
- 3. Pregnant or lactating women. (The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.) 4. Active hepatitis B or hepatitis C infection. 5. HIV/AIDS infection. 6. Uncontrolled active infection. 7. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- 8. Previously treatment with any gene therapy products. 9. Allergy to immunotherapy and associated drugs. 10. Patients with heart disease that is in need of treatment or with poorly controlled hypertension determined by investigators.
- 11. Patients with unstable or active ulceration or with gastrointestinal bleeding.
- 12. Patients with previous or planed organ transplantation. 13. Hyponatremia with concentration of sodium in the blood < 125 mmol/L. 14. Serum potassium (baseline) < 3.5 mmol/L (Patients can take potassium supplements to recover serum potassium level prior to participating the study).
- 15. Patients need anticoagulant (e.g. Warfarin or heparin). 16. Patients need long-term antiplatelet agent (Aspirin, dose > 300 mg/d; Clopidogrel, dose > 75 mg/d).
- 17. Any radiotherapy conducted within 4 weeks prior to blood sampling.
Trial locations and contacts
1 site in 1 country.
Honghui Huang, MD contact
China1 site
Renji Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, 200127
Honghui Huang, MD, honghui_huang@163.com
Fangyuan Chen, MD
About this study
Official title: Autologous T Cells With a Chimeric Antigen Receptor in Patients With CD19-positive Malignant B Cell Leukemia and Lymphoma
This study is designed for determining the safety and relative engraftment levels of the redirected autologous T cells transduced with the anti-CD19 lentiviral vector in patients with CD19-positive B cell leukemia and malignant lymphoma.
Read the detailed description
A single arm open-label pilot study is designed to determine the safety, tolerability and engraftment potential of CAR-CD19 T cells in patients with CD19-positive malignant B cell leukemia and lymphoma. All subjects will receive CAR-CD19 T cells infusion.
Primary objectives:
- Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19 lentiviral vector (referred to as "CAR-CD19 T" cells).
- Determine the duration of in vivo survival of CAR-CD19 T cells.
Secondary objectives:
- For patients with detectable disease, measure anti-tumor response due to CAR-CD19 T cells infusions.
- To determine the amplification and survival of CAR-CD19 T 4-1BB:CD3ζ and CD28:CD3ζ as measured by the relative engraftment levels of CAR-CD19 T 4-1BB:CD3ζ and CD28:CD3ζ cells over time.
- Estimate relative trafficking of CAR-CD19 T cells to tumors in bone marrow and lymphnodes.
- Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CAR-CD19 T (loss of engraftment).
- Determine the relative subsets of CAR-CD19 T cells.
- Being tested
- CAR-CD19 T cells, Fludarabine, Cyclophosphamide
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-CD19 T cellsGenetic
Also called CD19 Redirected Autologous Cells
Initial dose: A total of 1 - 10×10^7 CAR-CD19 T cells/kg will be administered by 1 - 3 infusions. Subsequent dose will be based on the subject's response to initial dose.
FludarabineDrug
30 mg/m^2/day×4 days
CyclophosphamideDrug
500 mg/m^2/day×2 days
| Study group | Role | What they receive |
|---|---|---|
| CAR-CD19 T cells | Experimental | Autologous T Cells with a CD19-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection. Lymphodepleting conditioning regimen: A combination of fludarabine and cyclophosphamide will be administered at Day -9 - Day -4. Receives: Genetic: CAR-CD19 T cells; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study related adverse events
Occurrence of study related adverse events, defined as NCI CTC ≥ Grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusional toxicity and any toxicity possibly related to the CAR-CD19 T cells.
Measured: 24 weeks
Secondary outcomes (3)
Primary engraftment endpoint
Duration of in vivo survival of CAR-CD19 T cells is defined as "engraftment". The primary engraftment endpoint is the # DNA vector copies per mg blood of CAR-CD19 T cells on week 4 after the first infusion. Q-PCR for CAR-CD19 T vector sequences will also be performed after infusion at 24 hours, weekly x 4, monthly x 6, and every 3 months thereafter until any 2 sequential tests are negative documenting loss of CAR-CD19 T cells.
Measured: 2 years
Anti-tumor responses
Describe anti-tumor responses to CAR-CD19 T cell infusions.
Measured: 2 years
Overall survival
Describe overall survival and cause of death.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2016 (estimated)
- Study startOct 2016
- Primary completionApr 2018 (estimated)
- Study completionJan 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CD19 Positive Malignant B-cell Leukemia and LymphomaStudies of the same condition, open and under way.
- More trials run by RenJi 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- CARsgen Therapeutics Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Fangyuan Chen, MD, Principal investigator, RenJi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02933775
- Sponsor's protocol ID
- CG3001
- Status last verified
- Oct 2016
- First submitted
- 13 Oct 2016
- Last updated
- 14 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PubMed 34515338
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous T Cells With a Chimeric Antigen Receptor in Patients With CD19-positive Malignant B Cell Leukemia and Lymphoma
- ClinicalTrials.gov ID
- NCT02933775
- Acronym / sponsor ID
- CG3001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Collaborators
- CARsgen Therapeutics Co., Ltd.
- Study start
- Oct 2016
- Primary completion
- Apr 2018 (estimated)
- Study completion
- Jan 2020 (estimated)
- First posted
- 14 Oct 2016 (estimated)
- 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.
This study is designed for determining the safety and relative engraftment levels of the redirected autologous T cells transduced with the anti-CD19 lentiviral vector in patients with CD19-positive B cell leukemia and malignant lymphoma.
Detailed description
A single arm open-label pilot study is designed to determine the safety, tolerability and engraftment potential of CAR-CD19 T cells in patients with CD19-positive malignant B cell leukemia and lymphoma. All subjects will receive CAR-CD19 T cells infusion.
Primary objectives:
- Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19 lentiviral vector (referred to as "CAR-CD19 T" cells).
- Determine the duration of in vivo survival of CAR-CD19 T cells.
Secondary objectives:
- For patients with detectable disease, measure anti-tumor response due to CAR-CD19 T cells infusions.
- To determine the amplification and survival of CAR-CD19 T 4-1BB:CD3ζ and CD28:CD3ζ as measured by the relative engraftment levels of CAR-CD19 T 4-1BB:CD3ζ and CD28:CD3ζ cells over time.
- Estimate relative trafficking of CAR-CD19 T cells to tumors in bone marrow and lymphnodes.
- Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CAR-CD19 T (loss of engraftment).
- Determine the relative subsets of CAR-CD19 T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-CD19 T cells | Experimental | Genetic: CAR-CD19 T cells, Drug: Fludarabine, Drug: CyclophosphamideAutologous T Cells with a CD19-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection. Lymphodepleting conditioning regimen: A combination of fludarabine and cyclophosphamide will be administered at Day -9 - Day -4. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subjects with documented CD19-positive malignant B cell leukemia and lymphoma.
- All tests results should comply with the above criteria. No continuing supportive care is received.
Key exclusion criteria (7 listed)
- 1. CD19-negative B cell leukemia or lymphoma. 2. Feasibility assessment during screening demonstrates < 5% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to αCD3/CD28 costimulation.
- 3. Pregnant or lactating women. (The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.) 4. Active hepatitis B or hepatitis C infection. 5. HIV/AIDS infection. 6. Uncontrolled active infection. 7. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- 8. Previously treatment with any gene therapy products. 9. Allergy to immunotherapy and associated drugs. 10. Patients with heart disease that is in need of treatment or with poorly controlled hypertension determined by investigators.
- 11. Patients with unstable or active ulceration or with gastrointestinal bleeding.
- 12. Patients with previous or planed organ transplantation. 13. Hyponatremia with concentration of sodium in the blood < 125 mmol/L. 14. Serum potassium (baseline) < 3.5 mmol/L (Patients can take potassium supplements to recover serum potassium level prior to participating the study).
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 |
|---|---|---|
| CAR-CD19 T cellsAlso: CD19 Redirected Autologous CellsInitial dose: A total of 1 - 10×10^7 CAR-CD19 T cells/kg will be administered by 1 - 3 infusions. Subsequent dose will be based on the subject's response to initial dose. | Genetic | CAR-CD19 T cells |
| Fludarabine30 mg/m^2/day×4 days | Drug | CAR-CD19 T cells |
| Cyclophosphamide500 mg/m^2/day×2 days | Drug | CAR-CD19 T cells |
Primary outcome
Study related adverse events
Time frame: 24 weeks
Occurrence of study related adverse events, defined as NCI CTC ≥ Grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusional toxicity and any toxicity possibly related to the CAR-CD19 T cells.
3 secondary outcomes
Primary engraftment endpoint
Time frame: 2 years
Anti-tumor responses
Time frame: 2 years
Overall survival
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2016.
- Derived from this study: PubMed 34515338Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
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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.
Honghui Huang, MD contact
Fangyuan Chen, MD principal investigator
RenJi Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAR-CD19 T cells, Fludarabine and Cyclophosphamide in people with CD19 Positive Malignant B-cell Leukemia and Lymphoma, run by RenJi 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 12 inclusion and 7 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 14 Oct 2016. 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 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.
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 Honghui Huang, MD (honghui_huang@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Study related adverse events (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02933775, which also lists 1 linked publication.
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 14 Oct 2016.