Hematopoietic/Lymphoid CancerPhase 1/2NCT01735604
Genetically Engineered Lymphocyte Therapy in Treating Patients With Lymphoma That is Resistant or Refractory to Chemotherapy
A Phase 1/2 study testing anti-CD20-CAR vector-transduced autologous T cells and genetically engineered lymphocyte therapy 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 gene that has been created in the laboratory into white blood cells may make the body build an 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 resistant or… Read more about this study
- Who is it for?
- Ages 18 to 90 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-CD20-CAR vector-transduced autologous T cells and genetically engineered lymphocyte therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- Jan 2013to Oct 2018
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- •Male and female subjects with CD20+ 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
- CD20+ leukemia or lymphoma
- ALL in CR2 or CR3 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 CD20+:
- At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy
- Stage III-IV disease
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- 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 as initial therapy will be eligible.
- Mantle cell lymphoma:
- Beyond 1st CR 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 CD20+:
- 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/AST < 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
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- 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/CD28 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, 1 recruiting
- Recruiting
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Han weidong, Doctor, +86-10-66937463, hanwdrsw@sina.com
Bo jian, Doctor, 86-10-13801257802, boj301@sina.com
About this study
Official title: Pilot Study of Redirected Autologous T Cells Transduced to Express A CD20-Specific Chimeric Immunoreceptor in Patient With Chemotherapy Resistant or Refractory CD20+ Leukemia and Lymphoma
RATIONALE: Placing a gene that has been created in the laboratory into white blood cells may make the body build an 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 resistant 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-CD20 vector (referred to as CART-20 cells).
II. Determine duration of in vivo survival of CART-20 cells. RT-PCR analysis of whole blood will be used to detect and quantify survival of CART-20 TCR zeta:4-1BB over time.
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-tumor response due to CART-20 cell infusions.
II. Estimate relative trafficking of CART-20 cells to tumor in bone marrow and lymph nodes.
III. For patients with stored or accessible tumor cells (such as patients with active CLL, ALL, etc) determine tumor cell killing by CART-20 cells in vitro.
IV. Determine if cellular or humoral host immunity develops against the murine anti-CD20, and assess correlation with loss of detectable CART-20 (loss of engraftment).
- Determine the relative subsets of CART-20 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned groups according to order of enrollment.
Patients receive anti-CD20-CAR lentivirus vector-transduced autologous T cells with 41BB-gamma vector for 3-5 days 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, Prolymphocytic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma
- Being tested
- anti-CD20-CAR vector-transduced autologous T cells, genetically engineered lymphocyte therapy
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-CD20-CAR vector-transduced autologous T cellsBiological
anti-CD20-CAR vector-transduced autologous T cells
genetically engineered lymphocyte therapyOther
genetically engineered lymphocyte therapy
| Study group | Role | What they receive |
|---|---|---|
| anti-CD20-CAR T cell | Experimental | Arm 1 Patients receive anti-CD20-CAR lentiviral vector-transduced autologous T cells with 41BB vector for 3-5 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: anti-CD20-CAR vector-transduced autologous T cells; Other: genetically engineered lymphocyte therapy |
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 CART-20 cell infusions
Measured: Baseline and post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2012 (estimated)
- Study startJan 2013
- Primary completionMay 2017 (estimated)
- Study completionOct 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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
- 50 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
- NCT01735604
- Sponsor's protocol ID
- CHN-PLAGH-BT-001
- Status last verified
- Sep 2015
- First submitted
- 23 Nov 2012
- Last updated
- 29 Sep 2015
- 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 34515338Zhang WY, Wang Y, Guo YL, Dai HR, Yang QM, Zhang YJ, Zhang Y, Chen MX, Wang CM, Feng KC, Li SX, Liu Y, Shi FX, Luo C, Han WD. Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Signal Transduct Target Ther. 2016 Mar 11;1:16002. doi: 10.1038/sigtrans.2016.2. eCollection 2016.
PubMed 29263894Wang Y, Zhang WY, Han QW, Liu Y, Dai HR, Guo YL, Bo J, Fan H, Zhang Y, Zhang YJ, Chen MX, Feng KC, Wang QS, Fu XB, Han WD. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16.
PubMed 25444722
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Redirected Autologous T Cells Transduced to Express A CD20-Specific Chimeric Immunoreceptor in Patient With Chemotherapy Resistant or Refractory CD20+ Leukemia and Lymphoma
- ClinicalTrials.gov ID
- NCT01735604
- Acronym / sponsor ID
- CHN-PLAGH-BT-001
- Conditions
- Hematopoietic/Lymphoid Cancer, Adult Acute Lymphoblastic Leukemia in Remission, B-cell Adult Acute Lymphoblastic Leukemia, B-cell Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- May 2017 (estimated)
- Study completion
- Oct 2018 (estimated)
- First posted
- 28 Nov 2012 (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.
RATIONALE: Placing a gene that has been created in the laboratory into white blood cells may make the body build an 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 resistant or refractory to chemotherapy.
Detailed description
PRIMARY OBJECTIVES:
- Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD20 vector (referred to as CART-20 cells).
II. Determine duration of in vivo survival of CART-20 cells. RT-PCR analysis of whole blood will be used to detect and quantify survival of CART-20 TCR zeta:4-1BB over time.
SECONDARY OBJECTIVES:
- For patients with detectable disease, measure anti-tumor response due to CART-20 cell infusions.
II. Estimate relative trafficking of CART-20 cells to tumor in bone marrow and lymph nodes.
III. For patients with stored or accessible tumor cells (such as patients with active CLL, ALL, etc) determine tumor cell killing by CART-20 cells in vitro.
IV. Determine if cellular or humoral host immunity develops against the murine anti-CD20, and assess correlation with loss of detectable CART-20 (loss of engraftment).
- Determine the relative subsets of CART-20 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned groups according to order of enrollment.
Patients receive anti-CD20-CAR lentivirus vector-transduced autologous T cells with 41BB-gamma vector for 3-5 days 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-CD20-CAR T cell | Experimental | Biological: anti-CD20-CAR vector-transduced autologous T cells, Other: genetically engineered lymphocyte therapyArm 1 Patients receive anti-CD20-CAR lentiviral vector-transduced autologous T cells with 41BB vector for 3-5 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- •Male and female subjects with CD20+ 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
Key exclusion criteria (10 listed)
- •Pregnant or lactating women
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-CD20-CAR vector-transduced autologous T cellsanti-CD20-CAR vector-transduced autologous T cells | Biological | anti-CD20-CAR T cell |
| genetically engineered lymphocyte therapygenetically engineered lymphocyte therapy | Other | anti-CD20-CAR T cell |
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 CART-20 cell infusions
Time frame: Baseline and post-infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2015.
- 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.
- Derived from this study: PubMed 29263894Zhang WY, Wang Y, Guo YL, Dai HR, Yang QM, Zhang YJ, Zhang Y, Chen MX, Wang CM, Feng KC, Li SX, Liu Y, Shi FX, Luo C, Han WD. Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Signal Transduct Target Ther. 2016 Mar 11;1:16002. doi: 10.1038/sigtrans.2016.2. eCollection 2016.
- Derived from this study: PubMed 25444722Wang Y, Zhang WY, Han QW, Liu Y, Dai HR, Guo YL, Bo J, Fan H, Zhang Y, Zhang YJ, Chen MX, Feng KC, Wang QS, Fu XB, Han WD. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16.
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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 anti-CD20-CAR vector-transduced autologous T cells and genetically engineered lymphocyte therapy 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 29 inclusion and 10 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 29 Sep 2015. 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 Han weidong, doctor (+86-10-66937463, hanwdrsw@sina.com), or a site near the patient. 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 NCT01735604, which also lists 3 linked publications.
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 29 Sep 2015.