Pediatric AML: ELU001 in Pediatric Subjects Who Have Relapsed and/or Refractory CBFA2T3-GLIS2-positive AML
This research study focuses on a rare type of acute myeloid leukemia (with the subtype CBFA2T3::GLIS2 that overexpresses folate receptor alpha (FRα) (a protein on the surface of leukemia cells)) that has relapsed or is refractory. Relapse means the cancer has come back after treatment. Refractory means the cancer does not respond to treatment.
ELU001 is a new chemical entity described as a C'Dot drug conjugate (CDC), consisting of payloads (exatecans) and targeting moieties (folic acid analogs) covalently bound by linkers to the C'Dot particle carrier. ELU001 will be the first drug-conjugate of its kind to be introduced into the clinic, a first in class, and a novel molecular entity.
|Condition or Disease
Treatment will be given for 2 cycles of 28 days, for a total treatment of 2 months. At the end of each treatment cycle, there is an evaluation to see how the leukemia is responding to therapy. After completing two cycles, patients may enter into the Optional Treatment Continuation Period if the doctor believes that there is clinical benefit.
This is a Dose Escalation Safety Study to identify the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D). This study will also evaluate the tolerability of ELU001. The drug is given by an infusion through a vein over a period of about one hour.
ELU001 is not a drug approved by the FDA (Food and Drug Administration) yet. But it is believed that ELU001 could play a role in stopping this type of leukemia from getting worse and offer a treatment option that may have less side effects. This is because it focuses on leukemic cells that have increased levels of FRα more than it targets healthy cells which express normal or no FRα.
Arms and Interventions
Dose Escalation: Escalating doses of ELU001
Folic-acid functionalized C'Dot-Drug-Conjugate (FA-CDC)
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of ELU001 [28 days]
Establish the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of ELU001 in pediatric patients with relapsed or refractory CBFA2T3::GLIS2 positive AML.
Secondary Outcome Measures
- Evaluate preliminary anti-leukemic activity of ELU001 [First dose of study drug until 42 days after last cycle.]
Proportion of evaluable patients having achieved at least one of the following Complete Remission per IWG (CRIWG) Complete Remission With Partial Recovery of Platelet Count (CRp) Complete Remission with Incomplete Blood Count Recovery (CRi) Complete Remission for Minimal Residual Disease (CRm) Duration of Complete Remission from CRIWG/CR/CRp/CRi to hematological relapse or death from any cause, whichever comes first
- Characterize the pharmacokinetics of ELU001 [First dose of study drug until 42 days after last cycle.]
Measure the concentration of ELU001 in the blood. This includes - Maximum Observed Concentration (Cmax), Time After Dosing at which Maximum Observed Concentration of Drug is Observed (tmax), Area Under the Curve to the End of the Dosing Period (AUC0-tau), and Area Under the Curve to the Last Measurable Concentration (AUC0-t), will be estimated. Other PK parameters, e.g., Terminal Elimination or Disposition Half-Life (T½), Volume of Distribution (Vd), Clearance Rate (CL), and C'Dot, payload on C'Dot
- Characterize the immunogenicity of ELU001 [First dose of study drug until 42 days after last cycle.]
Percent incidence of Anti-Drug Antibodies (ADA) formation in the blood assessed from baseline until End-of-Treatment (EOT).
Key Inclusion Criteria:
Patients must meet the following criteria to enroll in this study:
Infants (>1 month) and children (≤9 years) at time of enrollment.
Relapsed or refractory CBFA2T3::GLIS2 positive AML
CNS1 or CNS2 during screening
Performance Status: Lansky ≥ 50
Adequate Organ Function including liver, kidney, and heart
Key Exclusion Criteria:
Patients who meet any of the following are not eligible to enroll in this study:
AML associated with congenital syndromes such as Down syndrome, Fanconi anemia, Bloom syndrome, Kostmann syndrome or Diamond-Blackfan anemia, or bone marrow failure associated with inherited syndromes.
Acute promyelocytic leukemia.
Clinically significant active or chronic corneal disorder, particularly corneal epitheliopathy or any eye disorder that may predispose patient to this condition, or unable to comply with an age-appropriate ophthalmologic examination.
Prior treatment with folate receptor-targeting anti-cancer agent(s) ≤ 21 days (or 2 half-lives must have elapsed before enrollment, whichever is longer), or received investigational anti-cancer treatment ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, prior to starting study drug, whichever is shorter.
Contacts and Locations
LocationsNo locations specified.
Sponsors and Collaborators
- Elucida Oncology
- Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL)
Study Documents (Full-Text)None provided.