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

May 2, 2024 updated by: OrphAI Therapeutics

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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 × 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LAM-003
Open label LAM-003 at three sequentially increasing starting dose levels of 200, 300 and 450 mg.
Drug: Open Label LAM-003
LAM-003

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
At the end of the 28-day observation period for Cycle 1.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse Event Assessment
Time Frame: Weekly during the first 4 weeks and then every 4 weeks for up to 48 weeks.
Number and percentage of participants with an adverse event (AE).
Weekly during the first 4 weeks and then every 4 weeks for up to 48 weeks.
Maximum Plasma Concentration (Cmax)
Time Frame: Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days)
The pharmacokinetic parameter Cmax was determined in plasma for the active metabolite of LAM-003A and LAM-003 (prodrug)
Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days)
Time of Maximum Concentration [Tmax]
Time Frame: Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days)
The pharmacokinetic parameter Tmax was determined in plasma for the active metabolite of LAM-003A and LAM-003 (prodrug)
Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days)
Area Under the Curve [AUC]
Time Frame: Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days)
The pharmacokinetic parameter area under the concentration-time curve was determined in plasma for the active metabolite of LAM-003A and LAM-003 (prodrug). AUClast is the area under the concentration-time curve from time-zero to the time of the last quantifiable concentration. AUCtau is the area under the concentration-time curve during the dosing interval where tau=24hours for once daily (QD) dosing. AUCtau was not calculated for LAM-003.
Cycle 1 Days 1, 2 and 8 (1 cycle = 28 days)
Objective Response Rate
Time Frame: Every 8 to 12 weeks for up to 48 weeks.
Tumor response by AML response criteria (Cheson 2003).
Every 8 to 12 weeks for up to 48 weeks.
Event-Free Survival (EFS) and Overall Survival (OS)
Time Frame: Every 8 to 12 weeks for up to 48 weeks.
Event-free survival (EFS), defined as the interval from the start of study therapy to the earliest of the first documentation of disease relapse, disease progression, treatment failure (TF), or death from any cause. Overall survival (OS), defined as the interval from the start of study therapy to death from any cause.
Every 8 to 12 weeks for up to 48 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
OrphAI Therapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Langdon Miller, M.D., AI Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 16, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 20, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 5, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 5, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 8, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 3, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 2, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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