Clinical trial NCT05829226: A Phase 1 Study With LYT-200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS)
Official title: A Phase 1 Open-label, Multi-center Study of the Safety, Pharmacokinetics (PK), and Anti-tumor Activity of LYT- 200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: AML, Adult Recurrent
MDS
Keywords: AML Recurrent
AML Relapsed
AML Refractory
Hematological Cancer
Gal-9
Immuno-oncology
MDS
MDS High Risk
Lead sponsor: PureTech
Sponsor class: INDUSTRY
First posted: 2023-04-25
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A Phase 1 open-label, multi-center study. The 4+2 algorithm-based dose-escalation design in single agent LYT-200 and in combination with venetoclax and/or HMAs will be used to help identify the recommended Phase 2 dose (RP2D). Up to 6 patients per single treatment Cohorts 1-5 will receive infusions of LYT-200 every week (QW). Up to 6 patients per combination Cohorts 1-4 will receive infusions of LYT-200 QW and oral venetoclax every day and/or HMAs for 7 days (azacitidine) or 5 days (decitabine) per cycle.
Primary purpose: TREATMENT

Brief summary: A Phase 1 Open-label, Multi-center Study of the Safety, Pharmacokinetics (PK), and Anti-tumor Activity of LYT- 200 in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML), or with Relapsed/refractory, High-risk Myelodysplastic Syndrome (MDS)

Detailed description: This is an open-label, non-randomized, multi-center, Phase 1, dose escalation study in patients with AML relapsed/refractory to at least one line of prior therapy, with or without an allogeneic stem cell transplant, or in patients with a documented diagnosis of relapsed/refractory, high-risk myelodysplastic syndrome (MDS) post at least one line of treatment and for whom no standard therapy that may provide clinical benefit is available. The 4+2 algorithm-based dose-escalation design will be used to help identify the recommended Phase 2 dose (RP2D). Single agent LYT-200 and in combination with venetoclax and/or hypomethylating agents (HMA) safety and tolerability evaluation is the primary study endpoint, Pharmacokinetics (PK), and Anti-tumor Activity of LYT- 200 single agent and in combination with venetoclax and/or HMAs are key secondary study endpoints.

Eligibility criteria: Inclusion Criteria:

* Patients ≥ 18 years of age at the time of obtaining informed consent.
* Patients with morphologically documented primary or secondary AML by the World Health Organization(WHO) criteria, whose disease is relapsed/refractory to at least one line of prior therapy, with or without an allogeneic stem cell transplant and for whom no standard therapy that may provide clinical benefit is available or for patients who decline available standard of care.
* Patients with a documented diagnosis of high-risk myelodysplastic syndrome (MDS), whose disease is relapsed/refractory, post at least one line of treatment based on the revised International Prognostic Scoring System (IPSS-R) and for whom no standard therapy that may provide clinical benefit is available
* Patients are able and willing to comply with study procedures as per protocol, including bone marrowbiopsies.
* Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Patient must meet the following criteria as indicated on the clinical laboratory tests:

oWhite blood cell (WBC) count at the time of the first dose of \< 25,000/uL. oAspartate aminotransferase or alanine aminotransferase ≤ 3 × upper limit of normal (ULN; ≤ 5.0× ULN if considered to be due to leukemic involvement). oTotal bilirubin ≤ 2 × ULN (≤ 3 × ULN if considered to be due to leukemic involvement orGilbert's syndrome). oCreatinine clearance of ≥ 60 mL/min.

Exclusion Criteria:

* Patient diagnosed with acute promyelocytic leukemia (APL).
* Patient has active malignant tumors other than AML/MDS
* Patient has had HSCT and meets any of the following: has undergone HSCT within the 6- month period prior to the first study dose; has ≥ Grade 2 persistent non-hematological toxicity related to the transplant donor lymphocytes infusion.
* Patient has active graft versus host disease (GVHD) and patients receiving immunosuppressive treatment for GVHD.
* Patient with symptomatic central nervous system (CNS) involvement of leukemia or other CNS diseases related to underlying and secondary effects of malignancy
* Patient has had major surgery within 4 weeks prior to the first study dose.
* Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patient with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.
* Patient has any condition which, in the Investigator's opinion, makes the patient unsuitable for study participation.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and RP2D determination]
timeFrame: approximately 1 year
measure: Incidence of Dose Limiting Toxicities [Tolerability and RP2D determination]
timeFrame: approximately 1 year
Secondary outcomes:
measure: Rate of disease responses, time-to-event endpoints, hematological improvements
timeFrame: approximately 1 year
measure: Pharmacokinetic (PK) profile of LYT-200_Area Under the Curve (AUC)
timeFrame: approximately 1 year
measure: Pharmacokinetic (PK) profile of LYT-200_Concentration Max (CMax)
timeFrame: approximately 1 year
measure: Pharmacokinetic (PK) profile of LYT-200_Time to Reach CMax (TMax)
timeFrame: approximately 1 year
Other outcomes:
measure: Anti-Drug Antibody formation
timeFrame: approximately 1 year
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Miami
country: United States
facility: Baptist Health South Florida-Miami Cancer Institute
state: Florida
city: Louisville
country: United States
facility: Norton Healthcare-Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Mass. General Hospital-Harvard
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
Study officials:
affiliation: PureTech Health
name: Aleksandra Filipovic, MD, PhD.
role: STUDY_DIRECTOR
References: