Back to resultsA Study of LAM-003 in Patients With Acute Myeloid Leukemia
Primary Purpose
Oncology, Acute Myeloid Leukemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Open Label LAM-003
Sponsored by
About this trial
This is an interventional treatment trial for Oncology
Eligibility Criteria
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.
Sites / Locations
- Yale University
- University of Maryland
- Dana Farber Cancer Institute
- Hackensack Meridien Health
- Weill Cornell Medical College
- Virginia Cancer Specialists
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LAM-003
Arm Description
Open label LAM-003 at three increasing dose levels of 200, 300 and 450 mg.
Outcomes
Primary Outcome Measures
Maximum tolerated dose (MTD)
MTD as determined by incidence of dose-limiting toxicities (DLTs)
Secondary Outcome Measures
Adverse event assessment
Incidence of adverse events
Pharmacokinetics (PK)
Drug concentrations in plasma
Anti-tumor activity
Tumor response by acute myeloid leukemia response criteria (Cheson 2003).
Genetic profile of acute myeloid leukemia blasts
Changes in genetic profiles of acute myeloid leukemia blasts as measured by next-generation sequencing (NGS).
Protein profile of acute myeloid leukemia blasts.
Changes in protein profiles of acute myeloid leukemia blasts as measured by protein immunoblotting.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03426605
Brief Title
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
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
January 16, 2018 (Actual)
Primary Completion Date
February 20, 2020 (Actual)
Study Completion Date
October 5, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OrphAI Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oncology, Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Open Label, Dose-Escalation
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LAM-003
Arm Type
Experimental
Arm Description
Open label LAM-003 at three increasing dose levels of 200, 300 and 450 mg.
Intervention Type
Drug
Intervention Name(s)
Open Label LAM-003
Intervention Description
LAM-003
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)
Description
MTD as determined by incidence of dose-limiting toxicities (DLTs)
Time Frame
At the end of the 28-day treatment cycle.
Secondary Outcome Measure Information:
Title
Adverse event assessment
Description
Incidence of adverse events
Time Frame
Weekly during the first 4 weeks and then every 4 weeks for up to 48 weeks.
Title
Pharmacokinetics (PK)
Description
Drug concentrations in plasma
Time Frame
During Cycle 1 Visit Days 1, 2, and 8.
Title
Anti-tumor activity
Description
Tumor response by acute myeloid leukemia response criteria (Cheson 2003).
Time Frame
Every 8 to 12 weeks for up to 48 weeks..
Title
Genetic profile of acute myeloid leukemia blasts
Description
Changes in genetic profiles of acute myeloid leukemia blasts as measured by next-generation sequencing (NGS).
Time Frame
During Cycle 1 Visits Days 1,2, 8 and 15.
Title
Protein profile of acute myeloid leukemia blasts.
Description
Changes in protein profiles of acute myeloid leukemia blasts as measured by protein immunoblotting.
Time Frame
During Cycle 1 Visits Days 1,2, 8 and 15.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Langdon Miller, M.D.
Organizational Affiliation
LAM Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Hackensack Meridien Health
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://ai-therapeutics.com
Description
Trial information can be found on AI Therapeutics website
Learn more about this trial
A Study of LAM-003 in Patients With Acute Myeloid Leukemia
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