Non-Hodgkin LymphomaPhase 1NCT03666000
Dose-escalation and Dose-expansion Study of Safety of Azer-cel (PBCAR0191) in Participants With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)
A Phase 1 study testing Azer-cel, Fludarabine and Cyclophosphamide in people with Non-Hodgkin Lymphoma and B-cell Acute Lymphoblastic Leukemia, run by Imugene Limited at 15 sites in 2 countries.
Trial summary
This is a Phase 1/1b, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of azer-cel, an allogeneic anti-CD19 CAR T, in adults with r/r B ALL, r/r B-cell NHL and CLL/SLL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma, B-cell Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia
- What is being tested?
- Azer-cel, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 11 Mar 2019to Jun 2027
- Phase
- Phase 1
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 B-ALL:
- Participant has confirmed unequivocal r/r CD19+ B-ALL.
- Criteria for NHL and CLL/SLL:
- Participant has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by tumor biopsy tissue from last relapse after CD19-directed therapy.
- For Phase 1 Dose Escalation:
- Diffuse large B-cell lymphoma (DLBCL) including Richter's transformation
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- Follicular lymphoma (FL) including Grade 3 or transformed FL
- High-grade B-cell lymphoma (HGBCL)
- Primary mediastinal lymphoma
- For Phase 1b Dose Expansion (CAR T-relapsed cohort):
- DLBCL not otherwise specified (NOS)
- HGBCL
- DLBCL transformed from the following indolent lymphoma subtypes (FL, Marginal Zone lymphoma [MZL], and Waldenstrom's Macroglobulinemia [WM])
- Other large B-cell lymphoma (LBCL) subtypes may be enrolled with approval from the Medical Monitor.
- Participants previously treated with CD19-directed autologous CAR T therapies have received no more than 2 lines of therapy after administration of their previous CAR T product.
- For the expansion CAR T-relapsed cohort only: Participants must have received autologous CD19-directed CAR T therapy and demonstrated clinical response to the treatment at Day 28 or later, followed by relapse or progression.
- For Phase 1b dose expansion (CAR T-naive cohort and Con-BTKi cohort):
- For indication with an approved autologous CAR T-cell therapy, participants must be ineligible for or unable to access autologous CAR T-cell therapy.
- DLBCL NOS
- DLBCL transformed from the following indolent lymphoma subtypes (FL, MZL, and WM)
- HGBCL
- FL (Grade 1-3a)
- MZL that is fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET) scan
- WM
- CLL/SLL
- Primary central nervous system (CNS) lymphoma (PCNSL)
- Other LBCL subtypes may be enrolled with approval from the Medical Monitor.
- Participant must have received at least 1-2 prior lines of therapy, depending on histological subtype but no more than 7 systemic lines of anti-cancer therapy.
- Participants enrolling into the Con-BTKi cohort must:
- Be receiving a BTKi (as a monotherapy or combination therapy) as the last, systemic anti-cancer regimen before study entry. Alternatively, if previously refractory to one or more BTK inhibitor(s) and the last systemic anti-cancer therapy before study entry did not include a BTKi, one of the previous BTK inhibitors may be used.
- Have radiologic or clinical disease progression while on the BTKi
- Agree to remain on BTKi therapy during the protocol-defined BTKi treatment window
- Have been tolerant to BTKi therapy
- Criteria for both B-ALL, NHL, and CLL/SLL:
- Eastern Cooperative Oncology Group performance status score of 0 or 1.
- An estimated life expectancy of at least 12 weeks according to the investigator's judgment.
- Seronegative for human immunodeficiency virus antibody.
- Participant has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
Who cannot join
- Criteria for B-ALL:
- Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.
- Criteria for NHL:
- Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
- Active hemolytic anemia.
- Criteria for B-ALL and NHL:
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- No active CNS disease, excluding PCNSL
- History of another primary malignancy
- Any form of primary immunodeficiency (for example, severe combined immunodeficiency disease).
- History of hepatitis B or hepatitis C currently receiving ongoing antiviral therapy.
- Any known uncontrolled cardiovascular disease at the time of Screening that, in the investigator's opinion, renders the participant ineligible
- History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Presence of a CNS disorder that, in the opinion of the investigator, renders the participant ineligible for treatment.
- History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.
- Active uncontrolled autoimmune disease requiring active immunosuppression at the time of Screening (excluding participants needing steroids for physiologic replacement).
- Participant has received stem cell transplant within 90 days before Screening.
- Participant has active graft-versus-host disease (GvHD) symptoms.
- Participant has received a systemic biologic agent for treatment of the disease under study within 28 days of LD, other systemic anti-cancer therapy within 10 days or 5 half-lives (whichever is shorter) of LD, and no pulse steroid for disease control within 3 days of LD.
- Radiotherapy within 4 weeks before Screening.
- Presence of pleural/peritoneal/pericardial catheter, as well as permeant biliary and ureteral stents (does not apply to intravenous lines).
- Participant has received live vaccine within 4 weeks before Screening. Note: Non-live virus vaccines are not excluded.
- Participant has received CD19-directed therapy other than autologous CD19-directed CAR T therapy within 90 days of the anticipated start date of LD.
- Additional criteria apply.
Trial locations and contacts
15 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
15 sites in 2 countries
United States10 sites, 10 recruiting
- Recruiting
Winship Cancer Institute Emory University
Atlanta, Georgia, 30322
Clinical Trials
Edmund Waller, MD
- Recruiting
Northside Hospital Cancer Institute
Atlanta, Georgia, 30342
Clinical Trials
Scott Solomon, MD
- Recruiting
University of Maryland
Baltimore, Maryland, 21201
Clinical Trials
Jean Yared, MD
- Recruiting
Tufts Medical Center
Boston, Massachusetts, 02111
Clinical Trials
Andreas Klein, MD
- Recruiting
Baylor University Medical Center
Dallas, Texas, 75246
Clinical Trials
Houston Holmes III, MD
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Clinical Trials
Nirav Shah, MD
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55455
Clinical Research
Supriya Gupta, MD
- Recruiting
Columbia University Irving Medical Center/New York Presbyterian Hospital
New York, New York, 10032
Clinical Trials
Ran Reshef, MD
- Recruiting
Lifespan Cancer Institute at Rhode Island Hospital
Providence, Rhode Island, 02903
Clinical Trials
Adam Olszewski, MD
- Recruiting
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
Clinical Research
Bijal Shah, MD
Australia5 sites, 5 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Dr Danielle Blunt
- Recruiting
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Dr Vinay Vanguru
- Recruiting
St Vincent's Hospital Melbourne
Fitzroy, Victoria, 3065
Matthew Ku
- Recruiting
Barwon Health - Andrew Love Cancer Centre
Geelong, Victoria, 3320
Hannah Rose
- Recruiting
Liverpool Hospital
Liverpool, New South Wales, 2170
Dr Nagendra P Sungala
About this study
Official title: A Phase 1/1b, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate Safety and Clinical Activity of PBCAR0191 (Azercabtagene Zapreleucel or "Azer-cel") in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)
This is a Phase 1/1b, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of azer-cel, an allogeneic anti-CD19 CAR T, in adults with r/r B ALL, r/r B-cell NHL and CLL/SLL.
Read the detailed description
This is a multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and tolerability, find an appropriate dose to optimize safety and efficacy, and evaluate clinical activity of azer-cel in participants with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Before initiating azer-cel, participants will be administered lymphodepletion (LD). At Day 0 of the Treatment Period, participants will receive an intravenous (IV) infusion of azer-cel potentially followed by interleukin-2 (IL-2). All participants will be monitored through D720 or progression. All participants who receive a dose of azer-cel will be asked to consent to a separate long-term follow-up (LTFU) study for up to 15 years after exiting this study.
- Conditions
- Non-Hodgkin Lymphoma, B-cell Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- Being tested
- Azer-cel, Fludarabine, Cyclophosphamide, IL-2, Ibrutinib, Acalabrutinib, Zanubrutinib, or Pirtobrutinib
- Medical subject headings
- Lymphoma, Non-Hodgkin, Burkitt Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azer-celBiological
Also called Allogeneic Anti-CD19 CAR T cells, PBCAR0191
Infusion of Allogeneic Anti-CD19 CAR T cells
FludarabineDrug
Specified dose on specified days
CyclophosphamideDrug
Specified dose on specified days
IL-2Drug
Specified dose on specified days
Ibrutinib, Acalabrutinib, Zanubrutinib, or PirtobrutinibDrug
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Dose Escalation: Azer-cel Dose Level 1 | Experimental | Azer-cel, 3 x 10^5 CAR T cells per kilogram (kg) body weight.
Route of Administration: Intravenous infusion Receives: Biological: Azer-cel; Drug: Fludarabine; Drug: Cyclophosphamide |
| Phase 1 Dose Escalation: Azer-cel Dose Level 2 | Experimental | Azer-cel, 1 x 10^6 CAR T cells per kg body weight.
Route of Administration: Intravenous infusion Receives: Biological: Azer-cel; Drug: Fludarabine; Drug: Cyclophosphamide |
| Phase 1 Dose Escalation: Azer-cel Dose Level 3a | Experimental | Azer-cel, 3 x 10^6 CAR T cells per kg body weight.
Route of Administration: Intravenous infusion Receives: Biological: Azer-cel; Drug: Fludarabine; Drug: Cyclophosphamide |
| Phase 1 Dose Escalation: Azer-cel Dose Level 4 | Experimental | Azer-cel, 6 x 10^6 CAR T cells per kg body weight as 2 administrations of 3 x 10^6 CAR T cells per kg body weight on Day 0 and Day 10.
Route of Administration: Intravenous infusion Receives: Biological: Azer-cel; Drug: Fludarabine; Drug: Cyclophosphamide |
| Phase 1 Dose Escalation: Azer-cel Dose Level 4b | Experimental | Azer-cel, 500 x 10^6 CAR T cells (flat dose).
Route of Administration: Intravenous infusion Receives: Biological: Azer-cel; Drug: Fludarabine; Drug: Cyclophosphamide |
| Phase 1B Dose Expansion: Azer-cel | Experimental | Azer-cel will be administered at a dose level established in Phase 1.
Route of Administration: Intravenous infusion Receives: Biological: Azer-cel; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: IL-2 |
| Phase 1B Dose Expansion: Azer-cel + Bruton's tyrosine kinase inhibitor | Experimental | Azer-cel will be administered at a dose level established in Phase 1.
Route of Administration: Intravenous infusion
In combination with a Bruton's tyrosine kinase inhibitor Receives: Biological: Azer-cel; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: IL-2; Drug: Ibrutinib, Acalabrutinib, Zanubrutinib, or Pirtobrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1 Dose Escalation/Phase 1b Dose Expansion: Number of Participants with Azer-cel-related AEs Defined as Dose-limiting Toxicities (DLTs)
Measured: Up to Day 720
Phase 1b Dose Expansion: Objective Response Rate (ORR) B-ALL
ORR for participants with B-ALL will be assessed by National Comprehensive Cancer Network (NCCN) 2017 criteria.
Measured: Up to Day 720
Phase 1b Dose Expansion: ORR NHL
ORR for participants with NHL will be assessed by Lugano classification, International Workgroup on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines, International Primary Central Nervous System Lymphoma Collaborative Group (IPCG) criteria, and International Workshop on Waldenstrom's Macroglobulinemia (IWWM)-11 criteria.
Measured: Up to Day 720
Secondary outcomes (7)
Phase 1 Dose Escalation: ORR
- B-ALL: NCCN 2017 criteria
- NHL: Lugano classification
Measured: Up to Day 720
Complete Response (CR) Rate
- B-ALL: NCCN 2017 criteria
- NHL: Lugano classification
Measured: Up to day 720
Duration of Response (DoR)
- Defined as the duration (days) from initial response to disease progression or death.
Measured: Up to day 720
Progression-free survival (PFS)
- Defined as the duration (days) from Day 0 to disease progression or death.
Measured: Up to day 720
Overall survival (OS)
- Defined as the duration (days) from Day 0 to death.
Measured: Up to day 720
Time to next treatment (TNT)
- Defined as the duration (days) from Day 0 to institution of next systemic therapy.
Measured: Up to day 720
Number of Participants with AEs
- Defined as all AEs of clinical significance captured on study and specific reporting of DLTs, treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interests (AESIs), and AEs related to study treatment.
Measured: Up to day 720
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2018
- Study start11 Mar 2019
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin LymphomaStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imugene Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Byon, MD, PhD, Study chair, Imugene Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03666000
- Sponsor's protocol ID
- PBCAR0191-01
- Status last verified
- Sep 2026
- First submitted
- 20 Aug 2018
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No