Acute Myeloid Leukemia, AML, Refractory Acute Myeloid Leukemia
Conditions
Keywords
Relapsed Acute Myeloid Leukemia
Brief summary
This is a first in human, multi center, open label, phase 1/1b study to evaluate the safety and preliminary efficacy of CER-1236 in patients with relapsed/refractory (R/R), measurable residual disease (MRD) positive acute myeloid leukemia (AML), or TP53mut disease.
Detailed description
CER-1236 is a first in class chimeric engulfment receptor T-cell therapy candidate that targets the Tim4 ligand. This is a first in human, multi center, open label, phase 1/1b study to evaluate the safety and preliminary efficacy of CER-1236 in patients with relapsed/refractory (R/R), measurable residual disease (MRD) positive acute myeloid leukemia (AML), or TP53mut disease. The study is divided into Part 1 (escalation phase) and Part 2 (expansion phase). Part 1 (Escalation Phase): The primary objectives of Part 1 are to define the safety of different doses of CER-1236 and to define the recommended dose for Part 2 (RP2D) of CER-1236. Part 2 (Expansion Phase): The objective of the Part 2 expansion cohort is to evaluate the safety and efficacy of CER-1236 in patients with acute myeloid leukemia.
Interventions
DRUGCER-1236
an autologous chimeric engulfment receptor T-cell
DRUGCyclophosphamide
Lymphodepleting chemotherapy
DRUGFludarabine
Lymphodepleting chemotherapy
DRUGMesna
Chemoprotectant
Sponsors
CERo Therapeutics Holdings, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multiple ascending dose and dose expansion study of CER-1236 administered as a single agent.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients need to have a confirmed diagnosis of de novo or secondary AML, or myelodysplastic syndrome (MDS)/AML with 10% to 19% blasts, per the International Consensus Classification 2022 or the WHO 2022 classification. * Absolute lymphocyte count \>0.3 x 109/L prior to apheresis. * Eastern cooperative oncology group (ECOG) performance status 0 to 1.
Exclusion criteria
* Prior therapy with a permanently integrated, genetically modified cell product. * No measurable leukemia on the screening bone marrow evaluation prior to any bridging therapy. * Active autoimmune disease or history of autoimmune disease requiring treatment within the prior 2 years. Patients with history of autoimmune thyroiditis or type 1 diabetes well controlled on replacement regimen are eligible. * A known hypersensitivity or severe allergy to fludarabine, cyclophosphamide, or study drug components or diluents. * Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the physician. * Primary immunodeficiency disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Part 1) | 2 year | Escalation Period |
| Incidence of dose-limiting toxicities (DLTs) of CER-1236 Monotherapy - (Part 1) | 28 days | Escalation Period |
| Estimation of the objective response rate (ORR), complete response (CR), composite complete response (cCR), and measurable residual disease (MRD) negativity rates - (Part 2) | 2 years | Expansion Period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimation of the objective response rate (ORR), complete response (CR), composite complete response (cCR), and measurable residual disease (MRD) negativity rates - (Part 1) | 2 years | Escalation Period |
| PK (Cmax) of CER-1236 - (Part 1) | 2 years | Escalation Period |
| PK (AUC) of CER-1236 - (Part 1) | 2 year | Escalation Period |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) - (Part 2) | 2 years | Expansion Period |
Countries
United States
Outcome results
None listed