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

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

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

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Oncology
• Intervention / Treatment: Drug: Open Label LAM-003

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 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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Meridien Health
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 × 109/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 is 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: AI Therapeutics, Inc.
• Investigators: Study Director: Langdon Miller, M.D., LAM Therapeutics

Publications and helpful links

Helpful Links

• Trial information can be found on AI Therapeutics website

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2018
• Primary Completion (Actual): February 20, 2020
• Study Completion (Actual): October 5, 2020

Study Registration Dates

• First Submitted: January 5, 2018
• First Submitted That Met QC Criteria: February 7, 2018
• First Posted (Actual): February 8, 2018

Study Record Updates

• Last Update Posted (Actual): December 20, 2021
• Last Update Submitted That Met QC Criteria: December 17, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: LAM-003-HEM-CLN02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No