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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03426605
• Other study ID #: LAM-003-HEM-CLN02
• Status: Completed
• Phase: Phase 1
• Start date: January 16, 2018
• Est. completion date: October 5, 2020

Study information

• Verified date: May 2024
• Source: OrphAI Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: October 5, 2020
• Est. primary completion date: February 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Oncology

Intervention

Drug:
• Open Label LAM-003
LAM-003

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Hackensack Meridien Health	Hackensack	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Weill Cornell Medical College	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
OrphAI Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	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	Adverse Event Assessment	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.
Secondary	Maximum Plasma Concentration (Cmax)	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)
Secondary	Time of Maximum Concentration [Tmax]	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)
Secondary	Area Under the Curve [AUC]	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)
Secondary	Objective Response Rate	Tumor response by AML response criteria (Cheson 2003).	Every 8 to 12 weeks for up to 48 weeks.
Secondary	Event-Free Survival (EFS) and Overall Survival (OS)	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.

External Links

•   Trial information can be found on AI Therapeutics website