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)
- Conditions
- AML, Adult RecurrentMDS
- Interventions
- Registration Number
- NCT05829226
- Lead Sponsor
- PureTech
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Combination agent dose escalation LYT-200 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. Single agent dose escalation LYT-200 LYT-200 in relapsed/refractory AML or relapsed/refractory high-risk MDS, administered via IV infusion over 60 minutes every week. Combination agent dose escalation Venetoclax 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. Combination agent dose escalation Azacitidine 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. Combination agent dose escalation Decitabine 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.
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events [Safety and RP2D determination] approximately 1 year 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
Incidence of Dose Limiting Toxicities [Tolerability and RP2D determination] approximately 1 year 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
- Secondary Outcome Measures
Name Time Method Pharmacokinetic (PK) profile of LYT-200_Area Under the Curve (AUC) approximately 1 year Characterize the PK profile of LYT-200
Rate of disease responses, time-to-event endpoints, hematological improvements approximately 1 year Evaluate preliminary efficacy of LYT- 200 as a single agent in AML and MDS
Pharmacokinetic (PK) profile of LYT-200_Concentration Max (CMax) approximately 1 year Characterize the PK profile of LYT-200
Pharmacokinetic (PK) profile of LYT-200_Time to Reach CMax (TMax) approximately 1 year Characterize the PK profile of LYT-200
Trial Locations
- Locations (9)
Mass. General Hospital-Harvard
🇺🇸Boston, Massachusetts, United States
Virginia Commonwealth University Medical Center
🇺🇸Richmond, Virginia, United States
Baptist Health South Florida-Miami Cancer Institute
🇺🇸Miami, Florida, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
Norton Healthcare-Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States