A Study of LAM-003 in Patients With Acute Myeloid Leukemia

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.

Inclusion criteria

• Men and women of age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• 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 1.
• 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.
• Willingness and ability of the subject to comply with study activities.
• Evidence of a personally signed informed consent document.

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).
• Ongoing severe graft-versus-house disease (GVHD) with Grade ≥2 serum bilirubin, Grade ≥3 skin involvement, or Grade ≥3 diarrhea at the start of study therapy.
• Prior solid organ transplantation.
• Ongoing immunosuppressive therapy other than corticosteroids.
• Use of a strong inhibitor or inducer of cytochrome P450 (CYP) 3A4.
• Use of a drug known to prolong the cardiac QT interval.
• Concurrent participation in another therapeutic or imaging clinical trial.
• Presence of a concomitant medical condition that (in the judgement of the investigator) interferes with the ability of the subject to participate in the study.