Relapsed or Refractory B-cell LymphomaPhase 1NCT03208556
Safety and Efficacy of iPD1 CD19 eCAR T Cells in Relapsed or Refractory B-cell Lymphoma
A Phase 1 study testing iPD1 CD19 eCAR T cells and Fludarabine and cyclophosphamide in people with Relapsed or Refractory B-cell Lymphoma, run by Peking University at 1 site in China.
Trial summary
PD1 pathway is critical in determining the response to CAR T cell therapy. Emerging data suggested that Inhibition of PD1 could enhance the efficacy of CAR T cell therapy. iPD1 CD19 eCAR T cells is an enhanced version of the classical 2nd generation anti-CD19 4-1BB-costimulatory chimeric antigen receptor engineered T… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Relapsed or Refractory B-cell Lymphoma
- What is being tested?
- iPD1 CD19 eCAR T cells and Fludarabine and cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 21 Jun 2017to 1 Jun 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- CD19+ B cell lymphoma,verified by IHC or flow cytometry.
- a prior history of at least one standard care of medication.
- ineligible for allogeneic transplantation or relapsed after transplantation.
- patients are 18 years older.
- life expectancy > 3months.
- ECOG ≤ 2.
Show all 10Show fewer
- satisfactory major organ functions: adequate heart function with LVEF≥50%; pulse oximetry of ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl .
- Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L.
- women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study.
- measurable tumors.
Who cannot join
- using immunosuppressive drugs or systemic steroids within one week of enrollment.
- active infection.
- HIV positive.
- active hepatitis B virus infection or hepatitis C virus infection.
- breastfeeding or pregnant women.
- patients refuse to practice birth control during study and one year post study.
Show all 9Show fewer
- patients with a prior history of other malignances will be excluded from this study, but patients who have been cured from skin basal cell carcinoma or cervical cancer, or who have had their tumors removed by surgical resection but without further therapies and have more than 5 years of progression-free survival, can be included into the study.
- currently enrolled in other study.
- patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.
Trial locations and contacts
1 site in 1 country.
Zhitao Ying, MD contact
China1 site, 1 recruiting
- Recruiting
Beijing Cancer Hosptical
Beijing
Zhitao Ying, MD, yingzhitao001@163.com
Jun Zhu, MD
About this study
Official title: Pilot Study of Autologous Anti-CD19 4-1BB CAR T Cells With Cell-intrinsic PD1 Inhibition in Relapsed or Refractory B-cell Lymphoma
PD1 pathway is critical in determining the response to CAR T cell therapy. Emerging data suggested that Inhibition of PD1 could enhance the efficacy of CAR T cell therapy. iPD1 CD19 eCAR T cells is an enhanced version of the classical 2nd generation anti-CD19 4-1BB-costimulatory chimeric antigen receptor engineered T cells with cell-intrinsic PD1 inhibition by incorporation of a PD1 shRNA-expressing cassette in the CAR lentivector. This design will enhance the anti-tumor activities of CAR T cells by inhibiting PD1 induction after CAR T cell activation. This pilot, single arm, one center, dose-escalation, open label study is to determine the safety and efficacy of iPD1 CD19 eCAR T cells in relapsed or refractory CD19 positive lymphoma.
Subjects will be given a lymphodepletion chemotherapy comprised of Fludarabine and cyclophosphamide prior to CAR T cell infusion. The chemotherapy is completed 1 to 4 days before the first dost of iPD1 CD19 eCAR T cells.
- Conditions
- Relapsed or Refractory B-cell Lymphoma
- Being tested
- iPD1 CD19 eCAR T cells, Fludarabine and cyclophosphamide
- Medical subject headings
- Recurrence, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iPD1 CD19 eCAR T cellsBiological
iPD1 CD19 eCAR T cells are administrated in a 3-day split-dose regimen （d0, 30%; d1, 30%; d2, 40%）.
CAR T cell dose escalation: 1×10^5 /kg，1×10^6 /kg，3×10^6 /kg，and 6×10^6 CAR T cells/kg
Fludarabine and cyclophosphamideDrug
Fludarabine 25 mg/m2 d1-3; cyclophosphamide 250 mg/m2 d1-3. Lymphodepletion chemotherapy is completed 1 to 4 days before CAR T cell infusion
| Study group | Role | What they receive |
|---|---|---|
| iPD1 CD19 eCAR T cells | Experimental | patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion Receives: Biological: iPD1 CD19 eCAR T cells; Drug: Fludarabine and cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0
incidents of treatment related adverse events per NCI CTCAE V4.0
Measured: 2 years
Secondary outcomes (3)
treatment response
The efficacy of infusion of iPD1 CD19 eCAR T cells is assessed according to the standardized response criteria for malignant lymphoma (Cheson BD, JCO, 2007), which is defined as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).
Measured: 6 months
overall survival
Overall survival is defined as the time from receiving iPD1 CD19 eCAR T cells infusion to death for any cause.
Measured: 3 years
progression-free survival
Progression-free survival (PFS) is defined as the time from receiving iPD1 CD19 eCAR T cell infusion to disease progression or death from any cause.
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 posted5 Jul 2017
- Study start21 Jun 2017
- Primary completion1 Jun 2019 (estimated)
- Study completion1 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Peking UniversityThe 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University
- Sponsor type
- University, hospital or other
- Collaborators
- Marino Biotechnology Co., Ltd.
- Responsible party
- Principal investigator, Jun Zhu, Peking University
- Investigators
- Jun Zhu, MD, Principal investigator, Peking University Cancer Hospital & InstituteZhitao Ying, MD, Study director, Peking University Cancer Hospital & InstituteXiaoyu Xiang, PhD, Study director, Marino Biotechnology Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03208556
- Sponsor's protocol ID
- 2017YJZ13
- Status last verified
- Jul 2017
- First submitted
- 27 Jun 2017
- Last updated
- 14 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Autologous Anti-CD19 4-1BB CAR T Cells With Cell-intrinsic PD1 Inhibition in Relapsed or Refractory B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT03208556
- Acronym / sponsor ID
- 2017YJZ13
- Conditions
- Relapsed or Refractory B-cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Peking UniversityUniversity, hospital or other
- Collaborators
- Marino Biotechnology Co., Ltd.
- Study start
- 21 Jun 2017 (actual)
- Primary completion
- 1 Jun 2019 (estimated)
- Study completion
- 1 Jun 2020 (estimated)
- First posted
- 5 Jul 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.
PD1 pathway is critical in determining the response to CAR T cell therapy. Emerging data suggested that Inhibition of PD1 could enhance the efficacy of CAR T cell therapy. iPD1 CD19 eCAR T cells is an enhanced version of the classical 2nd generation anti-CD19 4-1BB-costimulatory chimeric antigen receptor engineered T cells with cell-intrinsic PD1 inhibition by incorporation of a PD1 shRNA-expressing cassette in the CAR lentivector. This design will enhance the anti-tumor activities of CAR T cells by inhibiting PD1 induction after CAR T cell activation. This pilot, single arm, one center, dose-escalation, open label study is to determine the safety and efficacy of iPD1 CD19 eCAR T cells in relapsed or refractory CD19 positive lymphoma.
Subjects will be given a lymphodepletion chemotherapy comprised of Fludarabine and cyclophosphamide prior to CAR T cell infusion. The chemotherapy is completed 1 to 4 days before the first dost of iPD1 CD19 eCAR 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 |
|---|---|---|
| iPD1 CD19 eCAR T cells | Experimental | Biological: iPD1 CD19 eCAR T cells, Drug: Fludarabine and cyclophosphamidepatients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- CD19+ B cell lymphoma,verified by IHC or flow cytometry.
- a prior history of at least one standard care of medication.
- ineligible for allogeneic transplantation or relapsed after transplantation.
- patients are 18 years older.
- life expectancy > 3months.
Key exclusion criteria (9 listed)
- using immunosuppressive drugs or systemic steroids within one week of enrollment.
- active infection.
- HIV positive.
- active hepatitis B virus infection or hepatitis C virus infection.
- breastfeeding or pregnant 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 |
|---|---|---|
| iPD1 CD19 eCAR T cellsiPD1 CD19 eCAR T cells are administrated in a 3-day split-dose regimen （d0, 30%; d1, 30%; d2, 40%）. CAR T cell dose escalation: 1×10^5 /kg，1×10^6 /kg，3×10^6 /kg，and 6×10^6 CAR T cells/kg | Biological | iPD1 CD19 eCAR T cells |
| Fludarabine and cyclophosphamideFludarabine 25 mg/m2 d1-3; cyclophosphamide 250 mg/m2 d1-3. Lymphodepletion chemotherapy is completed 1 to 4 days before CAR T cell infusion | Drug | iPD1 CD19 eCAR T cells |
Primary outcome
safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0
Time frame: 2 years
incidents of treatment related adverse events per NCI CTCAE V4.0
3 secondary outcomes
treatment response
Time frame: 6 months
overall survival
Time frame: 3 years
progression-free 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 Sep 2017.
Related trials for Relapsed or Refractory B-cell Lymphoma
Active, not recruitingEarly Phase 1
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
B-ALL, DLBCL
RecruitingPhase 2
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
RecruitingPhase 1
A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab and a Combined Regimen of Mosunetuzumab and Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Active, not recruitingPhase 1
A Study of Radiation Therapy Before CAR T Cell Therapy for People With B Cell Lymphoma
Non-Hodgkin Lymphoma, Non-Hodgkin's Lymphoma, Relapsed
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.
Zhitao Ying, MD contact
Jun Zhu, MD principal investigator
Peking University Cancer Hospital & Institute
Zhitao Ying, MD study director
Peking University Cancer Hospital & Institute
Xiaoyu Xiang, PhD study director
Marino Biotechnology Co., Ltd.
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 iPD1 CD19 eCAR T cells and Fludarabine and cyclophosphamide in people with Relapsed or Refractory B-cell Lymphoma, run by Peking University 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 10 inclusion and 9 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 Sep 2017. 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 Jun Zhu, MD (+86-10-88196596, zj@bjcancer.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0 (time frame: 2 years). 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 14 Sep 2017; AzTrials last refreshed its copy on 7 Nov 2026.