This is a first-in-human dose escalation/dose expansion study to evaluate the safety and identify the best dose of modified immune cells, PRGN-3006 (autologous chimeric antigen receptor (CAR) T cells), in adult patients with relapsed or refractory acute myeloid leukemia (AML), Minimal Residual Disease (MRD) positive acute myeloid leukemia or higher risk myelodysplastic syndrome (MDS). Autologous CAR T cells are modified immune cells that have been engineered in the laboratory to specifically target a protein found on tumor cells and kill them.
This is a multi-center, nonrandomized, Phase 1/1b safety and tolerability study. The safety and tolerability of PRGN-3006 T cells will be assessed following intravenous administration of escalating doses in patients with relapsed or refractory CD33-positive AML, MRD-positive AML, or higher risk MDS. This study has completed the dose escalation phase and is further evaluating PRGN-3006 at the identified dose in the dose expansion phase.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
88
Participants will receive up to 2 intravenous (IV) administrations of PRGN-3006 T Cells with or without lymphodepletion and will be monitored for safety, efficacy, and correlative endpoints for up to 12 months following infusion.
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Mayo Clinic
Rochester, Minnesota, United States
Number of Participants who Experience Dose Limiting Toxicities (DLTs)
Incidence of dose limiting toxicity (DLT) as defined in the protocol
Time frame: Up to Day 42
Number of Participants who Experience Treatment Emergent Adverse Events (TEAEs)
Systemic toxicity in general and hematologic toxicity in specific will be assessed through the capture of TEAEs at each study visit and through laboratory assessments throughout the study. The severity of the TEAEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 scale.
Time frame: Up to 12 months post treatment
Disease Progression in AML Participants
Proportion of AML patients achieving partial response (PR), complete response (CR), CR with incomplete count recovery (CRi), and/or morphologic leukemia free state (MLFS) by ELN Response Criteria in AML. CRh will also be captured, defined as \<5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts.
Time frame: Up to 12 months post treatment
Disease Response in MDS Patients
Proportion of MDS patients achieving a response (CR, PR or Marrow CR) as defined in International Working Group (IWG) 2006 Criteria.
Time frame: Up to 12 months post treatment
Rate of Absolute Neutrophil Count Recovery
Rate of Absolute Neutrophil count recovery (\>0.5 x 10\^9/L)
Time frame: Day 28
Absolute Lymphocyte Count (ALC)
ALC including CD4/CD8 subsets by flow cytometry at baseline (at apheresis) in patients who have successful versus failed PRGN-3006 production.
Time frame: Baseline
Number of PRGN-3006 T Cells
Number of PRGN-3006 T Cells present in patients treated with PRGN-3006
Time frame: Up to 12 months post treatment
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