A Phase 1 Dose-Escalation Study of LAM-003 in Patients With Acute Myeloid Leukemia
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- OrphAI Therapeutics
- Enrollment
- 17
- Locations
- 6
- Primary Endpoint
- Maximum Tolerated Dose (MTD)
Overview
Brief Summary
A Phase 1 Dose-Escalation Study of LAM-003 in Patients with Acute Myeloid Leukemia
Detailed Description
This clinical trial is a Phase 1 study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of LAM-003 across a range of LAM-003 dose levels when administered to subjects with previously treated relapsed or refractory cute Myeloid Leukemia (AML).
Subjects will self-administer oral LAM-003 either once or twice per day as long as they are safely benefitting from therapy. Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of LAM-003 using a standard 3+3 dose-escalation design. Based on the pattern of dose-limiting toxicities observed in the first 4 weeks of therapy, escalation will proceed to define a recommended LAM-003 dosing regimen.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Men and women of age ≥18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Presence of measurable AML that has progressed during or relapsed after prior therapy
- •All acute toxic effects of any prior antitumor therapy resolved to Grade
- •Adequate hepatic profile.
- •Adequate renal function.
- •Adequate coagulation profile.
- •Negative antiviral serology for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C.
- •For female subjects of childbearing potential, a negative serum pregnancy test.
- •For both male and female subjects, willingness to use adequate contraception.
Exclusion Criteria
- •Leukemic blast cell count \>50 × 10\^9/L before the start of study therapy and despite the use hydroxyurea, cytarabine, and/or cyclophosphamide.
- •Presence of known central nervous system (CNS) leukemia.
- •Presence of another major cancer.
- •Ongoing Grade \>1 proliferative or nonproliferative retinopathy.
- •Significant cardiovascular disease or ECG abnormalities.
- •Significant gastrointestinal disease
- •Uncontrolled ongoing infection.
- •Pregnancy or breastfeeding.
- •Major surgery within 4 weeks before the start of study therapy.
- •Subject was a candidate for hematopoietic stem cell transplantation (HSCT).
Arms & Interventions
LAM-003
Open label LAM-003 at three sequentially increasing starting dose levels of 200, 300 and 450 mg.
Intervention: Open Label LAM-003 (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD)
Time Frame: At the end of the 28-day observation period for Cycle 1.
A primary objective was to determine the LAM-003 MTD and/or recommended dosing regimen (RDR) based on the pattern of dose-limiting toxicities (DLTs) in Cycle 1 of therapy. MTD as determined by DLTs.
Secondary Outcomes
- Adverse Event Assessment(Weekly during the first 4 weeks and then every 4 weeks for up to 48 weeks.)
- Time of Maximum Concentration [Tmax](Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days))
- Objective Response Rate(Every 8 to 12 weeks for up to 48 weeks.)
- Maximum Plasma Concentration (Cmax)(Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days))
- Event-Free Survival (EFS) and Overall Survival (OS)(Every 8 to 12 weeks for up to 48 weeks.)
- Area Under the Curve [AUC](Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days))