The study is a multicenter, open label Phase I/II trial. 1. To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 added to venetoclax for patients with CD33 positive relapsed/refractory AML. (Phase 1 portion) 2. To assess the percentage of patients with CR, CRh, or Overall Response (CR + CRh), up to 6 months after the start of treatment without receiving other AML therapies. (Phase 2 portion)
The study is a multicenter, open label Phase I and Phase II trial combining lintuzumab-Ac225 with venetoclax in patients who have relapsed or refractory AML. The Phase I portion is a dose-finding study which will enroll at least three patients at each dose level. Patients in a dose level will be observed for a minimum of 4 weeks before dose escalation occurs. There is no dose escalation for any individual patient. The Phase II portion of the study will enroll patients at the MTD dose level of lintuzumab-Ac225 as determined in the Phase I portion of the study. The goal of the Phase II portion will be to further characterize the safety and efficacy of the MTD dose of lintuzumab-Ac225.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
In the Phase I, patients will be enrolled into the following dose escalation cohorts: 0.50 μCi/kg, 1.0 μCi/kg, and 1.5 μCi/kg. If the 0.50 μCi/kg dose is determined to exceed the MTD, a 0.25 μCi/kg dose will be explored.
400 mg daily will be taken orally on Days 1-21 of a 28-day cycle. There will be a ramp up of venetoclax dosing in the first cycle, with 100 mg administered on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and Day 4 and later. Patients on antifungal azoles should receive one-half these doses, up to a maximum of 200 mg of venetoclax.
25 mg by mouth daily, administered on Cycle 1 Day 15 and continued for 12 months after the subject's last treatment with lintuzumab-Ac225.
University of California
Los Angeles, California, United States
RECRUITINGUniversity of Louisville
Louisville, Kentucky, United States
RECRUITINGOchsner Clinic Foundation
New Orleans, Louisiana, United States
Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225
To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 added to venetoclax for patients with CD33 positive relapse/refractory AML.
Time frame: Cycle 1, up to 48 days
Phase II: Overall Response (CR + CRh + CRi)
To assess the percentage of patients with CR, CRh, CRi or Overall Response (CR + CRh + CRi), up to 6 months after the start of treatment without receiving other AML therapies.
Time frame: Up to 6 months
Phase I: Overall Response
Number of patients who's overall response is CR, CRh, or CRi
Time frame: Up to 6 months
Phase I and II: OS
Number of patients who died
Time frame: End of 6 months, 12 months, 2 years
Phase I and II: DFS
Disease-free survival
Time frame: End of 6 months, 12 months, 2 years
Phase I and II: Evaluate incidence of AEs and SAEs
Rate of AEs and SAEs, including infusion-related reactions
Time frame: Through study completion, up to 2 years
Phase I and II: Evaluate BH3 priming assay results
Summary of assay results
Time frame: Completion of Cycle 1, estimated 1 month
Phase I and II: MRD status
Number of patients who are MRD negative
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Weill Cornell Medicine
New York, New York, United States
RECRUITINGFred Hutchinson Cancer Research Center
Seattle, Washington, United States
RECRUITINGTime frame: From date of first dose until the date of first documented response, first assessment at 6 months
Phase I and II: Lab abnormalities (other than hematologic indices)
Summary of rate of Grade 3/4 lab abnormalities
Time frame: Through study completion, up to 2 years