Hematopoietic/Lymphoid CancerPhase 1/2NCT03185494
Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD22
A Phase 1/2 study testing anti-CD19/22-CAR vector-transduced T cells in people with Hematopoietic/Lymphoid Cancer and Adult Acute Lymphoblastic Leukemia in Remission, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells. Read more about this study
- Who is it for?
- Ages 5 to 70 years
- Conditions the study is for
- Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia
- What is being tested?
- anti-CD19/22-CAR vector-transduced T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2017to 1 Aug 2020
- 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 5 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male and female subjects with CD19/22+ B cell malignancies in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled CD19/22+ leukemia or lymphoma ALL in CR2(second complete remission) or CR3(third complete remission) and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor
- Follicular lymphoma, previously identified as CD19/22+:
- At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy Stage III-IV disease Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year) Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc)
- CLL:
- At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy. Patients with high risk disease manifested by deletion chromosome 17p will be eligible if they fail to achieve a CR to initial therapy or progress within 2 years of 1 prior Less than 2 years between last chemotherapy and progression (i.e. most recent progression free interval < 2 years) Not eligible or appropriate for conventional allogeneic SCT Patients who achieve only a partial response to FCR(fludarabine, cyclophosphamide and Rituxan) as initial therapy will be eligible.
- Mantle cell lymphoma:
Show all 9Show fewer
- Beyond 1st CR (complete remission) with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc...) Relapsed after prior autologous SCT B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT
- Diffuse large cell lymphoma, previously identified as CD19+:
- Residual disease after primary therapy and not eligible for autologous SCT Relapsed after prior autologous SCT Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate of conventional allogeneic or autologous SCT Expected survival > 12 weeks Creatinine < 2.5 mg/dl ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal Bilirubin < 2.0 mg/dl Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy Adequate venous access for apheresis, and no other contraindications for leukapheresis Voluntary informed consent is given
Who cannot join
- 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 Uncontrolled active infection Active hepatitis B or hepatitis C infection Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary Previously treatment with any gene therapy products Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation Any uncontrolled active medical disorder that would preclude participation as outlined HIV infection
Trial locations and contacts
1 site in 1 country.
China1 site
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
About this study
Official title: Clinical Study of CD19/CD22 Tan CAR T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.
PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to chemotherapy.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19/CD22 vector (referred to as tanCART-19/22 cells).
II. Determine duration of in vivo survival of tanCART-19/22 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of tanCART-19/22TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-tumor response due to tanCART-19/22 cell infusions.
II. CD137 transgene is measured by the relative engraftment levels of tanCART-19/22 CD137 and TCR zeta cells over time.
III. Estimate relative trafficking of tanCART-19/22 cells to tumor in bone marrow and lymph nodes.
IV. For patients with stored or accessible tumor cells (such as patients with active chronic lymphocytic leukemia(CLL), acute lymphocytic leukemia (ALL), etc) determine tumor cell killing by tanCART-19/22 cells in vitro.
- Determine if cellular or humoral host immunity develops against the murine anti-CD19/22, and assess correlation with loss of detectable tanCART-19/20 (loss of engraftment).
VI. Determine the relative subsets of tanCART-19/22 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive anti-CD19/22-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.
- Conditions
- Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia, B-Cell Chronic Lymphocytic Leukemia in Relapse (Diagnosis), Prolymphocytic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma
- Being tested
- anti-CD19/22-CAR vector-transduced T cells
- Medical subject headings
- Hematologic Neoplasms, Disease, Leukemia, Prolymphocytic, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-CD19/22-CAR vector-transduced T cellsBiological
Also called genetically engineered lymphocyte therapy
genetically engineered lymphocyte therapy
| Study group | Role | What they receive |
|---|---|---|
| anti-CD19/22 CAR T cells | Experimental | Patients receive anti-CD19/22-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity. Receives: Biological: anti-CD19/22-CAR vector-transduced T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of study related adverse events
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
Measured: Until week 24
Secondary outcomes (1)
Anti-tumor responses to tanCART19/22 cell infusions
Measured: up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study start1 Aug 2017
- Primary completion1 Aug 2019 (estimated)
- Study completion1 Aug 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 Hematopoietic/Lymphoid CancerStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 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
- NCT03185494
- Sponsor's protocol ID
- CHN-PLAGH-BT-022
- Status last verified
- Jul 2018
- First submitted
- 10 Jun 2017
- Last updated
- 17 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Dai H, Wu Z, Jia H, Tong C, Guo Y, Ti D, Han X, Liu Y, Zhang W, Wang C, Zhang Y, Chen M, Yang Q, Wang Y, Han W. Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia. J Hematol Oncol. 2020 Apr 3;13(1):30. doi: 10.1186/s13045-020-00856-8.
PubMed 32245502
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of CD19/CD22 Tan CAR T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas
- ClinicalTrials.gov ID
- NCT03185494
- Acronym / sponsor ID
- CHN-PLAGH-BT-022
- Conditions
- Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia, B-Cell Chronic Lymphocytic Leukemia in Relapse (Diagnosis), Prolymphocytic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 1 Aug 2019 (estimated)
- Study completion
- 1 Aug 2020 (estimated)
- First posted
- 14 Jun 2017 (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.
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.
PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to chemotherapy.
Detailed description
PRIMARY OBJECTIVES:
- Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19/CD22 vector (referred to as tanCART-19/22 cells).
II. Determine duration of in vivo survival of tanCART-19/22 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of tanCART-19/22TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-tumor response due to tanCART-19/22 cell infusions.
II. CD137 transgene is measured by the relative engraftment levels of tanCART-19/22 CD137 and TCR zeta cells over time.
III. Estimate relative trafficking of tanCART-19/22 cells to tumor in bone marrow and lymph nodes.
IV. For patients with stored or accessible tumor cells (such as patients with active chronic lymphocytic leukemia(CLL), acute lymphocytic leukemia (ALL), etc) determine tumor cell killing by tanCART-19/22 cells in vitro.
- Determine if cellular or humoral host immunity develops against the murine anti-CD19/22, and assess correlation with loss of detectable tanCART-19/20 (loss of engraftment).
VI. Determine the relative subsets of tanCART-19/22 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive anti-CD19/22-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| anti-CD19/22 CAR T cells | Experimental | Biological: anti-CD19/22-CAR vector-transduced T cellsPatients receive anti-CD19/22-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 5 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female subjects with CD19/22+ B cell malignancies in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled CD19/22+ leukemia or lymphoma ALL in CR2(second complete remission) or CR3(third complete remission) and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor
- At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy Stage III-IV disease Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year) Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc)
- At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy. Patients with high risk disease manifested by deletion chromosome 17p will be eligible if they fail to achieve a CR to initial therapy or progress within 2 years of 1 prior Less than 2 years between last chemotherapy and progression (i.e. most recent progression free interval < 2 years) Not eligible or appropriate for conventional allogeneic SCT Patients who achieve only a partial response to FCR(fludarabine, cyclophosphamide and Rituxan) as initial therapy will be eligible.
- Beyond 1st CR (complete remission) with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc...) Relapsed after prior autologous SCT B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT
- Residual disease after primary therapy and not eligible for autologous SCT Relapsed after prior autologous SCT Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate of conventional allogeneic or autologous SCT Expected survival > 12 weeks Creatinine < 2.5 mg/dl ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal Bilirubin < 2.0 mg/dl Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy Adequate venous access for apheresis, and no other contraindications for leukapheresis Voluntary informed consent is given
Key exclusion criteria (1 listed)
- 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 Uncontrolled active infection Active hepatitis B or hepatitis C infection Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary Previously treatment with any gene therapy products Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation Any uncontrolled active medical disorder that would preclude participation as outlined HIV infection
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 |
|---|---|---|
| anti-CD19/22-CAR vector-transduced T cellsAlso: genetically engineered lymphocyte therapygenetically engineered lymphocyte therapy | Biological | anti-CD19/22 CAR T cells |
Primary outcome
Occurrence of study related adverse events
Time frame: Until week 24
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
1 secondary outcome
Anti-tumor responses to tanCART19/22 cell infusions
Time frame: up to 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2019.
- Derived from this study: PubMed 32245502Dai H, Wu Z, Jia H, Tong C, Guo Y, Ti D, Han X, Liu Y, Zhang W, Wang C, Zhang Y, Chen M, Yang Q, Wang Y, Han W. Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia. J Hematol Oncol. 2020 Apr 3;13(1):30. doi: 10.1186/s13045-020-00856-8.
- Individual participant dataSharing planned: Yes
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 anti-CD19/22-CAR vector-transduced T cells in people with Hematopoietic/Lymphoid Cancer and Adult Acute Lymphoblastic Leukemia in Remission, 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 9 inclusion and 1 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 17 Apr 2019. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of study related adverse events (time frame: Until week 24). 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 NCT03185494, 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 17 Apr 2019.