Status and phase
Conditions
Treatments
About
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 and r/r B-cell NHL.
Full 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) and non-Hodgkin lymphoma (NHL). 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. All participants will be monitored through D720 or progression. All participants who receive a dose of azer-cel will be followed in a separate long-term follow-up (LTFU) study for up to 15 years after exiting this study.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Key Inclusion Criteria
Criteria for B-ALL:
Criteria for NHL:
Participant has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by archived tumor biopsy tissue from last relapse after CD19-directed therapy and corresponding pathology report. Alternatively, if at least 1 tumor involved site is accessible at time of Screening, the participant's diagnosis is confirmed by pretreatment biopsy (excisional when possible) or by flow cytometry of fine needle aspirate (FNA). If a participant never had a CR, a sample from the most recent biopsy is acceptable. NHL subtypes included but are not limited to:
For Phase 1 Dose Escalation:
For Phase 1b Dose Expansion:
Participant has measurable or detectable (for example positron emission tomography-positive) disease according to the Lugano Classification.
Participant must have received at least 2 lines of prior anti-cancer therapy for the disease under study, including at least 1 chemoimmunotherapy regimen (e.g., anti-CD20 monoclonal antibody plus chemotherapy), consistent with standard of care treatment guidance (e.g., National Comprehensive Cancer Network [NCCN]), unless no second line therapy of known benefit exists for a given subject. For Richter's transformation, only 1 prior line of therapy is required for the DLBCL component.
Participant has received no more than 7 systemic lines of anti-cancer therapy for the disease under study.
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.
Expansion 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.
Criteria for both B-ALL and NHL:
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 (i.e., intact immune function).
Participant has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
Key Exclusion Criteria
Criteria for B-ALL:
Criteria for NHL:
Criteria for B-ALL and NHL:
No active central nervous system (CNS) disease. Subjects with a prior history of CNS involvement that has been adequately treated ≥3 months prior to study consent and without symptoms or clinical suspicion of relapsed CNS disease may be enrolled.
History of another primary malignancy that has not been in remission for at least 2 years with the following exceptions:
Curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the breast or cervix
Low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time
Completely resected Stage 1 solid tumor with low risk for recurrence within 2 years
In the case of Richter's transformation, participants may be enrolled with ongoing chronic lymphocytic leukemia/small lymphocytic lymphoma.
Any form of primary immunodeficiency (e.g., 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, including but not limited to:
History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening. In case of hypertensive crisis caused by omission of well-established treatment regimen, transient and promptly stabilized, enrollment must be discussed and agreed upon with sponsor and medical monitor.
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.
Abnormal findings during the Screening Period or any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the participant's safety.
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 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. Note: This criterion does not apply if the subject has clear evidence of disease progression after such an agent has been administered and all AEs have resolved to a Grade 2 or less in severity. This should be discussed with the Medical Monitor for confirmation
Radiotherapy within 4 weeks before Screening should be discussed with monitor and determined on a case-by-case basis.
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. 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
Primary purpose
Allocation
Interventional model
Masking
129 participants in 6 patient groups
Loading...
Central trial contact
Imugene Clinical Team
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal