Non-Hodgkin's Lymphoma, RelapsedPhase 1/2NCT04030195
Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL
A Phase 1/2 study testing PBCAR20A, Fludarabine and Cyclophosphamide in people with Non-Hodgkin's Lymphoma, Relapsed and Chronic Lymphoid Leukemia in Relapse, run by Precision BioSciences, Inc. at 5 sites in United States.
Trial summary
This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR20A in adult subjects with r/r B-cell NHL or r/r CLL/SLL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Relapsed, Chronic Lymphoid Leukemia in Relapse, Non-Hodgkin's Lymphoma Refractory
- What is being tested?
- PBCAR20A, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 5 sitesUnited States
- Study dates
- 24 Mar 2020to 24 Jun 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Criteria for NHL:
- r/r CD20+ B-cell NHL that is histologically confirmed by archived tumor biopsy tissue from the last relapse and corresponding pathology report.
- Measurable or detectable disease according to the Lugano classification.
- Primary refractory disease or r/r disease after a response to 2 prior regimens.
- Criteria for CLL/SLL:
- Diagnosis of CD20+ CLL with indication for treatment based on the iwCLL guidelines and clinically measurable disease or SLL with measurable disease that is biopsy-proven SLL.
Show all 10Show fewer
- Previously failed/tolerant to at least 2 prior lines of systemic targeted therapy of known benefit.
- Criteria for both NHL and CLL/SLL:
- Study participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Study participant has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
Who cannot join
- Criteria for NHL:
- Requirement for urgent therapy due to mass effects such as bowel obstruction, spinal cord, or blood vessel compression.
- Active central nervous system (CNS) disease. A negative computed tomography (CT)/magnetic resonance imaging (MRI) is required at Screening if the study participant has a history of CNS lymphoma.
- Criteria for NHL and CLL/SLL:
- Active CNS disease. A negative lumbar puncture is required at Screening if the study participant has a history of CNS disease.
- Previous malignancy, besides the malignancies of inclusion (B-cell NHL or CLL/SLL), that in the investigator's opinion, has a high risk of relapse in the next 2 years.
Show all 20Show fewer
- Active uncontrolled fungal, bacterial, viral, protozoal, or other infection.
- Any form of primary immunodeficiency.
- History of human immunodeficiency virus (HIV) infection.
- Active hepatitis B or C.
- Uncontrolled cardiovascular disease.
- Hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.
- Presence of a CNS disorder that renders ineligible for treatment.
- History of a genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman Diamond syndrome, or any other known bone marrow failure syndrome.
- Received ASCT within 45 days of Screening if the study participant has met the rest of the count requirements.
- Must not have received systemic corticosteroid therapy for at least 7 days prior to initiating lymphodepletion chemotherapy.
- Received a live vaccine within 4 weeks before Screening.
- Radiotherapy within 4 weeks determined on a case-by-case basis.
- Presence of a pleural/peritoneal/pericardial catheter.
- Current use of any anticoagulant or antiplatelet therapy.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Cleveland Clinic
Cleveland, Ohio, 44195
City of Hope
Duarte, California, 91010
MD Anderson Cancer Center
Houston, Texas, 77030
Columbia University
New York, New York, 10032
Stanford University
Stanford, California, 94305
About this study
Official title: A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR20A in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR20A in adult subjects with r/r B-cell NHL or r/r CLL/SLL.
Read the detailed description
This is a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate safety, tolerability, clinical activity, and find an appropriate dose to optimize safety and efficacy of PBCAR20A in subjects with relapsed/refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Before initiating PBCAR20A, therapy, subjects will be administered lymphodepletion chemotherapy composed of fludarabine and cyclophosphamide. At Day 0 of the Treatment Period, subjects will receive a single intravenous (IV) infusion of PBCAR20A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of PBCAR20A will be followed in a separate long-term follow-up (LTFU) study for 15 years after exiting this study.
- Conditions
- Non-Hodgkin's Lymphoma, Relapsed, Chronic Lymphoid Leukemia in Relapse, Non-Hodgkin's Lymphoma Refractory, Chronic Lymphocytic Leukemia, Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic
- Being tested
- PBCAR20A, Fludarabine, Cyclophosphamide
- Medical subject headings
- Lymphoma, Non-Hodgkin, Recurrence, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBCAR20AGenetic
Also called Allogeneic Anti-CD20 CAR T cells
Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.
FludarabineDrug
Fludarabine is used for lymphodepletion (30 mg/m^2/day, Days -5 to -3).
CyclophosphamideDrug
Cyclophosphamide is used for lymphodepletion (500 mg/m^2/day, Days -5 to -3).
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 of PBCAR20A CAR T cells | Experimental | 1 x 10^6 chimeric antigen receptor (CAR) T cells per kg body weight.
In this study, PBCAR20A, allogeneic anti-cluster of differentiation (CD20) CAR T Cells, is used to treat patients with relapsed or refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).
Route of Administration: Intravenous infusion (IV)
Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion. Receives: Genetic: PBCAR20A; Drug: Fludarabine; Drug: Cyclophosphamide |
| Dose Level 2 of PBCAR20A CAR T cells | Experimental | 240 x 10^6 CAR T cells (flat dose) Receives: Genetic: PBCAR20A; Drug: Fludarabine; Drug: Cyclophosphamide |
| Dose Level 3 of PBCAR20A CAR T cells | Experimental | 480 x 10^6 CAR T cells (flat dose) Receives: Genetic: PBCAR20A; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
The maximum tolerated dose (MTD) is the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy.
Measured: Day 1 to Day 28
Number of Participants With Dose-Limiting Toxicities
Dose-limiting toxicities (DLT) are certain Grade 3 and Grade 4 toxic reactions as defined by the protocol and CTCAE v5.0.
Measured: 1 year
Secondary outcomes (2)
Objective Response Rate
Objective response rate (ORR) is a measure of clinical activity as response in NHL by the revised Lugano Classification (Cheson et al, 2016) or a response in CLL/SLL by the International Workshop on Chronic Lymphocytic Leukemia 2018 guidelines.
Measured: 1 year
Progression-free Survival (PFS)
Progression-free survival is defined as the duration (days) from Day 0 to disease progression or death.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2019
- Study start24 Mar 2020
- Primary completion24 Jun 2021
- Study completion24 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Hodgkin's Lymphoma, RelapsedStudies of the same condition, open and under way.
- 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
- Sequential
- Model description
- Phase 1: Participants with r/r CD20+ B-cell NHL or r/r CLL/SLL will be enrolled to 3 escalating dose groups and treated sequentially, with the possibility of a single de-escalation. Within each dose group, at least 3 and at most 6 study participants will be treated with a single dose of PBCAR20A using a standard 3 + 3 design. The starting dose of PBCAR20A will be 1 × 10\^6 chimeric antigen receptor (CAR) T cells/kg body weight. Subsequent dose groups will be treated with escalating doses to a maximum dose of 480 × 10\^6 CAR T cells (flat dose). In the absence of dose-limiting toxicities (DLTs) (as described in Section 3.8 of the protocol), the dose will be increased using a fixed-dose scheme. Phase 2: Study PBCAR20A-01 did not proceed into Phase 2.
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Precision BioSciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alan List, MD, Study chair, Precision BioSciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04030195
- Sponsor's protocol ID
- PBCAR20A-01
- Status last verified
- Jan 2023
- First submitted
- 19 Jul 2019
- Last updated
- 31 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR20A in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
- ClinicalTrials.gov ID
- NCT04030195
- Acronym / sponsor ID
- PBCAR20A-01
- Conditions
- Non-Hodgkin's Lymphoma, Relapsed, Chronic Lymphoid Leukemia in Relapse, Non-Hodgkin's Lymphoma Refractory, Chronic Lymphocytic Leukemia, Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Precision BioSciences, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Mar 2020 (actual)
- Primary completion
- 24 Jun 2021 (actual)
- Study completion
- 24 Jun 2021 (actual)
- First posted
- 23 Jul 2019 (actual)
- Results
- Posted 31 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR20A in adult subjects with r/r B-cell NHL or r/r CLL/SLL.
Detailed description
This is a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate safety, tolerability, clinical activity, and find an appropriate dose to optimize safety and efficacy of PBCAR20A in subjects with relapsed/refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Before initiating PBCAR20A, therapy, subjects will be administered lymphodepletion chemotherapy composed of fludarabine and cyclophosphamide. At Day 0 of the Treatment Period, subjects will receive a single intravenous (IV) infusion of PBCAR20A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of PBCAR20A will be followed in a separate long-term follow-up (LTFU) study for 15 years after exiting this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Phase 1: Participants with r/r CD20+ B-cell NHL or r/r CLL/SLL will be enrolled to 3 escalating dose groups and treated sequentially, with the possibility of a single de-escalation. Within each dose group, at least 3 and at most 6 study participants will be treated with a single dose of PBCAR20A using a standard 3 + 3 design. The starting dose of PBCAR20A will be 1 × 10^6 chimeric antigen receptor (CAR) T cells/kg body weight. Subsequent dose groups will be treated with escalating doses to a maximum dose of 480 × 10^6 CAR T cells (flat dose). In the absence of dose-limiting toxicities (DLTs) (as described in Section 3.8 of the protocol), the dose will be increased using a fixed-dose scheme. Phase 2: Study PBCAR20A-01 did not proceed into Phase 2.
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 of PBCAR20A CAR T cells | Experimental | Genetic: PBCAR20A, Drug: Fludarabine, Drug: Cyclophosphamide1 x 10^6 chimeric antigen receptor (CAR) T cells per kg body weight. In this study, PBCAR20A, allogeneic anti-cluster of differentiation (CD20) CAR T Cells, is used to treat patients with relapsed or refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Route of Administration: Intravenous infusion (IV) Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion. |
| Dose Level 2 of PBCAR20A CAR T cells | Experimental | Genetic: PBCAR20A, Drug: Fludarabine, Drug: Cyclophosphamide240 x 10^6 CAR T cells (flat dose) |
| Dose Level 3 of PBCAR20A CAR T cells | Experimental | Genetic: PBCAR20A, Drug: Fludarabine, Drug: Cyclophosphamide480 x 10^6 CAR T cells (flat dose) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- r/r CD20+ B-cell NHL that is histologically confirmed by archived tumor biopsy tissue from the last relapse and corresponding pathology report.
- Measurable or detectable disease according to the Lugano classification.
- Primary refractory disease or r/r disease after a response to 2 prior regimens.
- Diagnosis of CD20+ CLL with indication for treatment based on the iwCLL guidelines and clinically measurable disease or SLL with measurable disease that is biopsy-proven SLL.
- Previously failed/tolerant to at least 2 prior lines of systemic targeted therapy of known benefit.
Key exclusion criteria (20 listed)
- Requirement for urgent therapy due to mass effects such as bowel obstruction, spinal cord, or blood vessel compression.
- Active central nervous system (CNS) disease. A negative computed tomography (CT)/magnetic resonance imaging (MRI) is required at Screening if the study participant has a history of CNS lymphoma.
- Active CNS disease. A negative lumbar puncture is required at Screening if the study participant has a history of CNS disease.
- Previous malignancy, besides the malignancies of inclusion (B-cell NHL or CLL/SLL), that in the investigator's opinion, has a high risk of relapse in the next 2 years.
- Active uncontrolled fungal, bacterial, viral, protozoal, or other 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 |
|---|---|---|
| PBCAR20AAlso: Allogeneic Anti-CD20 CAR T cellsSingle dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied. | Genetic | Dose Level 1 of PBCAR20A CAR T cells, Dose Level 2 of PBCAR20A CAR T cells, Dose Level 3 of PBCAR20A CAR T cells |
| FludarabineFludarabine is used for lymphodepletion (30 mg/m^2/day, Days -5 to -3). | Drug | Dose Level 1 of PBCAR20A CAR T cells, Dose Level 2 of PBCAR20A CAR T cells, Dose Level 3 of PBCAR20A CAR T cells |
| CyclophosphamideCyclophosphamide is used for lymphodepletion (500 mg/m^2/day, Days -5 to -3). | Drug | Dose Level 1 of PBCAR20A CAR T cells, Dose Level 2 of PBCAR20A CAR T cells, Dose Level 3 of PBCAR20A CAR T cells |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Day 1 to Day 28
The maximum tolerated dose (MTD) is the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy.
Number of Participants With Dose-Limiting Toxicities
Time frame: 1 year
Dose-limiting toxicities (DLT) are certain Grade 3 and Grade 4 toxic reactions as defined by the protocol and CTCAE v5.0.
2 secondary outcomes
Objective Response Rate
Time frame: 1 year
Progression-free Survival (PFS)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Non-Hodgkin's Lymphoma, Relapsed
RecruitingPhase 1/2
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma
Lymphoma, Non-Hodgkin 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
RecruitingPhase 1/2
A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
Mature B-Cell Non-Hodgkin Lymphoma
RecruitingPhase 1
In VIVO CAR-T Therapy for Relapsed/Refractory Hematological Malignancies
B-Acute Lymphoblastic Leukemia, B Cell Non-Hodgkin's Lymphoma
RecruitingPhase 3
A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy
Large B-cell Lymphoma, Lymphoma, B-Cell
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.
Alan List, MD study chair
Precision BioSciences, Inc.
5 sites 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 PBCAR20A, Fludarabine and Cyclophosphamide in people with Non-Hodgkin's Lymphoma, Relapsed and Chronic Lymphoid Leukemia in Relapse, run by Precision BioSciences, Inc. at 5 sites in United States.
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 20 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: finished, as of the sponsor's last update on 31 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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?
Yes. Results are posted in the registry (first posted 31 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) (time frame: Day 1 to Day 28). The study lists 2 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 31 Jan 2023.