Clinical trial NCT03426605: A Study of LAM-003 in Patients With Acute Myeloid Leukemia
Official title: A Phase 1 Dose-Escalation Study of LAM-003 in Patients With Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Oncology
Acute Myeloid Leukemia
Lead sponsor: OrphAI Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-02-08
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Open Label, Dose-Escalation
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Men and women of age ≥18 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
3. Presence of measurable AML that has progressed during or relapsed after prior therapy
4. All acute toxic effects of any prior antitumor therapy resolved to Grade 1.
5. Adequate hepatic profile.
6. Adequate renal function.
7. Adequate coagulation profile.
8. Negative antiviral serology for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C.
9. For female subjects of childbearing potential, a negative serum pregnancy test.
10. For both male and female subjects, willingness to use adequate contraception.
11. Willingness and ability of the subject to comply with study activities.
12. Evidence of a personally signed informed consent document.

Exclusion Criteria:

1. Leukemic blast cell count \>50 × 10\^9/L before the start of study therapy and despite the use hydroxyurea, cytarabine, and/or cyclophosphamide.
2. Presence of known central nervous system (CNS) leukemia.
3. Presence of another major cancer.
4. Ongoing Grade \>1 proliferative or nonproliferative retinopathy.
5. Significant cardiovascular disease or ECG abnormalities.
6. Significant gastrointestinal disease
7. Uncontrolled ongoing infection.
8. Pregnancy or breastfeeding.
9. Major surgery within 4 weeks before the start of study therapy.
10. Subject was a candidate for hematopoietic stem cell transplantation (HSCT).
11. 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.
12. Prior solid organ transplantation.
13. Ongoing immunosuppressive therapy other than corticosteroids.
14. Use of a strong inhibitor or inducer of cytochrome P450 (CYP) 3A4.
15. Use of a drug known to prolong the cardiac QT interval.
16. Concurrent participation in another therapeutic or imaging clinical trial.
17. 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: At the end of the 28-day observation period for Cycle 1.
Secondary outcomes:
measure: Adverse Event Assessment
timeFrame: Weekly during the first 4 weeks and then every 4 weeks for up to 48 weeks.
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days)
measure: Time of Maximum Concentration [Tmax]
timeFrame: Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days)
measure: Area Under the Curve [AUC]
timeFrame: Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days)
measure: Objective Response Rate
timeFrame: Every 8 to 12 weeks for up to 48 weeks.
measure: Event-Free Survival (EFS) and Overall Survival (OS)
timeFrame: Every 8 to 12 weeks for up to 48 weeks.
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack Meridien Health
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
affiliation: AI Therapeutics
name: Langdon Miller, M.D.
role: STUDY_DIRECTOR
References: