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)

MDS Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05829226
• Other study ID #: LYT-200-2022-02
• Status: Recruiting
• Phase: Phase 1
• Start date: December 12, 2022
• Est. completion date: May 2025

Study information

• Verified date: March 2023
• Source: PureTech
• Contact: Chris Korth
• Phone: 617-982-2550
• Email: clinicaltrials[@]puretechhealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: May 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• AML, Adult Recurrent
• Leukemia, Myeloid, Acute
• MDS
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• LYT-200
monoclonal antibody (mAb), targeting galectin-9 protein
• Venetoclax
Bcl-2 inhibitor
• Azacitidine
Hypomethylating agent
• Decitabine
Hypomethylating agent

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
PureTech

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Anti-Drug Antibody formation	Assess the immunogenicity of LYT-200	approximately 1 year
Primary	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
Primary	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	Rate of disease responses, time-to-event endpoints, hematological improvements	Evaluate preliminary efficacy of LYT- 200 as a single agent in AML and MDS	approximately 1 year
Secondary	Pharmacokinetic (PK) profile of LYT-200_Area Under the Curve (AUC)	Characterize the PK profile of LYT-200	approximately 1 year
Secondary	Pharmacokinetic (PK) profile of LYT-200_Concentration Max (CMax)	Characterize the PK profile of LYT-200	approximately 1 year
Secondary	Pharmacokinetic (PK) profile of LYT-200_Time to Reach CMax (TMax)	Characterize the PK profile of LYT-200	approximately 1 year