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)

NCT05829226 | Completed Phase 1 FDA Drug

• 1 other identifier: LYT-200-2022-02
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 9

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)

Conditions

AML, Adult Recurrent; MDS

Keywords

AML Recurrent; AML Relapsed; AML Refractory; Hematological Cancer; Gal-9; Immuno-oncology; MDS; MDS High Risk

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and RP2D determination]

  Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, ECG, ECHO/MUGA, ECOG status

  approximately 1 year

• Incidence of Dose Limiting Toxicities [Tolerability and RP2D determination]

  Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, ECG, ECHO/MUGA, ECOG status

  approximately 1 year

Secondary Outcomes (4)

• Rate of disease responses, time-to-event endpoints, hematological improvements

  approximately 1 year

• Pharmacokinetic (PK) profile of LYT-200_Area Under the Curve (AUC)

  approximately 1 year

• Pharmacokinetic (PK) profile of LYT-200_Concentration Max (CMax)

  approximately 1 year

• Pharmacokinetic (PK) profile of LYT-200_Time to Reach CMax (TMax)

  approximately 1 year

Other Outcomes (1)

• Anti-Drug Antibody formation

  approximately 1 year

Study Arms (2)

Single agent dose escalation

EXPERIMENTAL

LYT-200 in relapsed/refractory AML or relapsed/refractory high-risk MDS, administered via IV infusion over 60 minutes every week.

Drug: LYT-200

Combination agent dose escalation

EXPERIMENTAL

LYT-200 in relapsed/refractory AML or relapsed/refractory high-risk MDS, administered via IV infusion over 60 minutes every week, in combination with oral venetoclax Day 1, 100 mg, Day 2, 200mg, Day 3-28, 400 mg and/or azacitidine, 75 mg/m2 subcutaneously given for 7 days per cycle or decitabine 20 mg/m2 IV for 5 days per cycle.

Drug: LYT-200; Drug: Venetoclax; Drug: Azacitidine; Drug: Decitabine

Interventions

Decitabine DRUG

Hypomethylating agent

Combination agent dose escalation

LYT-200 DRUG

monoclonal antibody (mAb), targeting galectin-9 protein

Combination agent dose escalation; Single agent dose escalation

Venetoclax DRUG

Bcl-2 inhibitor

Combination agent dose escalation

Azacitidine DRUG

Hypomethylating agent

Combination agent dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PureTech: lead

Study Sites (9)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

Baptist Health South Florida-Miami Cancer Institute

Miami, Florida, 02114, United States

Location

Norton Healthcare-Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Mass. General Hospital-Harvard

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23219, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

venetoclax; Azacitidine; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Aleksandra Filipovic, MD, PhD.

  PureTech Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 30, 2023
• First Posted: April 25, 2023
• Study Start: December 12, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 6, 2026

Record last verified: 2025-05

Locations

US (9)