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

Study Overview
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Brief Summary
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A Phase 1 Dose-Escalation Study of LAM-003 in Patients with Acute Myeloid Leukemia

Detailed Description
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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 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.

Official Title
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A Phase 1 Dose-Escalation Study of LAM-003 in Patients With Acute Myeloid Leukemia

Conditions
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Oncology, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Open Label LAM-003


Participation Criteria
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Eligibility Criteria
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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 × 109/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 is 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open Label, Dose-Escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAM-003<br>Open label LAM-003 at three increasing dose levels of 200, 300 and 450 mg. | Drug: Open Label LAM-003<br>* LAM-003<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | MTD as determined by incidence of dose-limiting toxicities (DLTs) | At the end of the 28-day treatment cycle. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event assessment | Incidence of adverse events | Weekly during the first 4 weeks and then every 4 weeks for up to 48 weeks. | 
| Pharmacokinetics (PK) | Drug concentrations in plasma | During Cycle 1 Visit Days 1, 2, and 8. | 
| Anti-tumor activity | Tumor response by acute myeloid leukemia response criteria (Cheson 2003). | Every 8 to 12 weeks for up to 48 weeks.. | 
| Genetic profile of acute myeloid leukemia blasts | Changes in genetic profiles of acute myeloid leukemia blasts as measured by next-generation sequencing (NGS). | During Cycle 1 Visits Days 1,2, 8 and 15. | 
| Protein profile of acute myeloid leukemia blasts. | Changes in protein profiles of acute myeloid leukemia blasts as measured by protein immunoblotting. | During Cycle 1 Visits Days 1,2, 8 and 15. |