Description:
A Phase 1 Dose-Escalation Study of LAM-003 in Patients with Acute Myeloid Leukemia
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
LAM-003-HEM-CLN02
- NCT ID:
NCT03426605
Conditions
- Oncology
- Acute Myeloid Leukemia
Interventions
| Drug | Synonyms | Arms |
|---|
| Open Label LAM-003 | | LAM-003 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| LAM-003 | Experimental | Open label LAM-003 at three increasing dose levels of 200, 300 and 450 mg. | |
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 × 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Maximum tolerated dose (MTD) |
| Time Frame: | At the end of the 28-day treatment cycle. |
| Safety Issue: | |
| Description: | MTD as determined by incidence of dose-limiting toxicities (DLTs) |
Secondary Outcome Measures
| Measure: | Adverse event assessment |
| Time Frame: | Weekly during the first 4 weeks and then every 4 weeks for up to 48 weeks. |
| Safety Issue: | |
| Description: | Incidence of adverse events |
| Measure: | Pharmacokinetics (PK) |
| Time Frame: | During Cycle 1 Visit Days 1, 2, and 8. |
| Safety Issue: | |
| Description: | Drug concentrations in plasma |
| Measure: | Anti-tumor activity |
| Time Frame: | Every 8 to 12 weeks for up to 48 weeks.. |
| Safety Issue: | |
| Description: | Tumor response by acute myeloid leukemia response criteria (Cheson 2003). |
| Measure: | Genetic profile of acute myeloid leukemia blasts |
| Time Frame: | During Cycle 1 Visits Days 1,2, 8 and 15. |
| Safety Issue: | |
| Description: | Changes in genetic profiles of acute myeloid leukemia blasts as measured by next-generation sequencing (NGS). |
| Measure: | Protein profile of acute myeloid leukemia blasts. |
| Time Frame: | During Cycle 1 Visits Days 1,2, 8 and 15. |
| Safety Issue: | |
| Description: | Changes in protein profiles of acute myeloid leukemia blasts as measured by protein immunoblotting. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Unknown status |
| Lead Sponsor: | AI Therapeutics, Inc. |
Last Updated
December 11, 2018
