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 1/1b, 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)
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Time periods mentioned: 15 years
- Procedures mentioned: Infusions
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "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 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."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This early study tests the safety of different doses of azer-cel and how well it works. Azer-cel uses donated immune cells changed to target cancer cells. It is for adults with certain B-cell blood cancers that came back or did not respond to treatment.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Have a qualifying B-cell blood cancer: acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphoma, or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The cancer must meet the study group's rules, including CD19 testing where required.
- Be fully active or able to walk and do light work, even if you cannot do hard physical activity.
- Be expected to live at least 12 weeks. Have a negative HIV antibody test and good enough bone marrow, kidney, liver, lung, and heart function.
- For the group whose cancer returned after CAR T treatment: have improved at day 28 or later after CD19 CAR T made from your own cells, then had cancer return or worsen.
- If previously treated with CD19 CAR T made from your own cells, have had no more than 2 treatment courses since that CAR T treatment.
- For the CAR T-naive and BTK inhibitor expansion groups: if CAR T made from your own cells is approved for your cancer, be unable to get it or not qualify for it.
- For those expansion groups: have had at least 1–2 prior treatment courses, depending on cancer type, and no more than 7 whole-body cancer treatment courses.
- For the BTK inhibitor group: meet the rules for prior use of this cancer medicine, have cancer that worsened while taking it, have tolerated it, and agree to keep taking it during the required time.
Who can't join
- Have Burkitt-type or mixed-lineage acute leukemia. For lymphoma, need urgent treatment because a tumor blocks the bowel or presses on blood vessels, or have active anemia caused by red blood cells breaking down.
- Have active cancer in the brain or spinal cord, except primary central nervous system lymphoma, or another brain or nervous system disorder that makes treatment unsafe.
- Have a history of another primary cancer, an inherited weak immune system, or a genetic condition that causes bone marrow failure.
- Have hepatitis B or C being treated with antiviral medicine, or uncontrolled autoimmune disease needing medicine to suppress the immune system, except replacement-dose steroids.
- Have uncontrolled heart or blood vessel disease that makes treatment unsafe, a severe blood pressure crisis within 3 months, or a past severe immediate allergic reaction to a study medicine.
- Have had a stem cell transplant within 90 days, or have active graft-versus-host disease, in which donated cells attack your body.
- Have received certain cancer medicines or steroids too recently before study preparation treatment, or radiation or a live vaccine within 4 weeks before screening. Other CD19-targeted treatment within 90 days is excluded, except CAR T made from your own cells.
- Have certain drainage tubes in the chest, belly, or around the heart, or permanent tubes in the bile ducts or tubes carrying urine from the kidneys. IV lines are allowed.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Key Inclusion Criteria 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 * 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. Key Exclusion Criteria 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: * 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.
Study sites (10)
FL
- H. Lee Moffitt Cancer Center · Tampa, FL 33612Clinical Research · Study contactBijal Shah, MD · Principal investigatorMore trials in Tampa
GA
- Winship Cancer Institute Emory University · Atlanta, GA 30322Clinical Trials · Study contactEdmund Waller, MD · Principal investigatorMore trials in Atlanta
- Northside Hospital Cancer Institute · Atlanta, GA 30342Clinical Trials · Study contactScott Solomon, MD · Principal investigatorMore trials in Atlanta
MA
- Tufts Medical Center · Boston, MA 02111Clinical Trials · Study contactAndreas Klein, MD · Principal investigatorMore trials in Boston
MD
- University of Maryland · Baltimore, MD 21201Clinical Trials · Study contactJean Yared, MD · Principal investigatorMore trials in Baltimore
MN
- University of Minnesota · Minneapolis, MN 55455Clinical Research · Study contactSupriya Gupta, MD · Principal investigatorMore trials in Minneapolis
NY
- Columbia University Irving Medical Center/New York Presbyterian Hospital · New York, NY 10032Clinical Trials · Study contactRan Reshef, MD · Principal investigatorMore trials in New York
RI
- Lifespan Cancer Institute at Rhode Island Hospital · Providence, RI 02903Clinical Trials · Study contactAdam Olszewski, MD · Principal investigatorMore trials in Providence
TX
- Baylor University Medical Center · Dallas, TX 75246Clinical Trials · Study contactHouston Holmes III, MD · Principal investigatorMore trials in Dallas
WI
- Medical College of Wisconsin · Milwaukee, WI 53226Clinical Trials · Study contactNirav Shah, MD · Principal investigatorMore trials in Milwaukee