Testing LYT-200 for patients with relapsed or refractory AML and high-risk MDS

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)

This study is testing a new drug called LYT-200 to see if it can help people with relapsed or hard-to-treat Acute Myeloid Leukemia or high-risk Myelodysplastic Syndrome feel better when other treatments haven't worked.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: PureTech (industry)
• Locations: 9 sites (Los Angeles, California and 8 other locations)
• Trial ID: NCT05829226 on ClinicalTrials.gov

What this trial studies

This Phase 1 open-label, multi-center study evaluates the safety, pharmacokinetics, and anti-tumor activity of LYT-200 in patients with relapsed or refractory Acute Myeloid Leukemia (AML) or high-risk Myelodysplastic Syndrome (MDS). The study employs a dose escalation design to determine the recommended Phase 2 dose, assessing LYT-200 both as a single agent and in combination with other treatments like venetoclax and hypomethylating agents. Patients eligible for the study must have previously undergone at least one line of therapy and have no standard treatment options available. The primary focus is on safety and tolerability, with secondary endpoints including pharmacokinetics and anti-tumor activity.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory AML or high-risk MDS who have not responded to prior treatments.

Not a fit: Patients with early-stage AML or MDS who have not yet received treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with limited alternatives for relapsed or refractory AML and high-risk MDS.

How similar studies have performed: Other studies have shown promise in targeting similar hematological cancers, but this specific approach with LYT-200 is novel.

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.

Where this trial is running

Los Angeles, California and 8 other locations

• Cedars-Sinai Medical Center — Los Angeles, California, United States (RECRUITING)
• University of California Irvine Medical Center — Orange, California, United States (RECRUITING)
• Baptist Health South Florida-Miami Cancer Institute — Miami, Florida, United States (RECRUITING)
• Norton Healthcare-Norton Cancer Institute — Louisville, Kentucky, United States (RECRUITING)
• Mass. General Hospital-Harvard — Boston, Massachusetts, United States (RECRUITING)
• Karmanos Cancer Institute — Detroit, Michigan, United States (RECRUITING)
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States (RECRUITING)
• Rhode Island Hospital — Providence, Rhode Island, United States (RECRUITING)
• Virginia Commonwealth University Medical Center — Richmond, Virginia, United States (RECRUITING)

Study contacts

• Study coordinator: Chris Korth

Conditions: AML, Adult Recurrent, MDS, AML Recurrent, AML Relapsed, AML Refractory, Hematological Cancer, Gal-9, Immuno-oncology