Venetoclax and Lintuzumab-Ac225 in AML Patients
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|ClinicalTrials.gov Identifier: NCT03867682|
Recruitment Status : Recruiting
First Posted : March 8, 2019
Last Update Posted : March 8, 2022
The study is a multicenter, open label Phase I/II trial.
- To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 added to venetoclax for patients with CD33 positive relapsed/refractory AML. (Phase 1 portion)
- 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)
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Relapsed Adult AML||Biological: Lintuzumab-Ac225 Drug: Venetoclax Drug: Spironolactone||Phase 1 Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Venetoclax and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML|
|Actual Study Start Date :||January 15, 2020|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||January 2023|
Experimental: Phase I and Phase II
Lintuzumab-Ac225 administered on Day 5 of each cycle for four cycles (unless in the 0.5 μCi/kg or 0.25 μCi/kg cohorts, where there is a potential for an additional four cycles, pending PI and Medical Monitor review).
Venetoclax taken on Days 1-21 of each cycle for up to 12 cycles.
Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery.
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.
Other Name: Actimab
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.
Other Name: Venclexta
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.
Other Name: Aldactone
- Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225 [ Time Frame: Cycle 1, up to 48 days ]To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 added to venetoclax for patients with CD33 positive relapse/refractory AML.
- Phase II: Overall Response (CR + CRh + CRi) [ Time Frame: Up to 6 months ]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.
- Phase I: Overall Response [ Time Frame: Up to 6 months ]Number of patients who's overall response is CR, CRh, or CRi
- Phase I and II: OS [ Time Frame: End of 6 months, 12 months, 2 years ]Number of patients who died
- Phase I and II: DFS [ Time Frame: End of 6 months, 12 months, 2 years ]Disease-free survival
- Phase I and II: Evaluate incidence of AEs and SAEs [ Time Frame: Through study completion, up to 2 years ]Rate of AEs and SAEs, including infusion-related reactions
- Phase I and II: Evaluate BH3 priming assay results [ Time Frame: Completion of Cycle 1, estimated 1 month ]Summary of assay results
- Phase I and II: MRD status [ Time Frame: From date of first dose until the date of first documented response, first assessment at 6 months ]Number of patients who are MRD negative
- Phase I and II: Lab abnormalities (other than hematologic indices) [ Time Frame: Through study completion, up to 2 years ]Summary of rate of Grade 3/4 lab abnormalities
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03867682
|Contact: Actinium Pharmaceuticals, Inc.||+firstname.lastname@example.org|
|United States, California|
|University of California||Recruiting|
|Los Angeles, California, United States, 90095|
|United States, Kentucky|
|University of Louisville||Recruiting|
|Louisville, Kentucky, United States, 40202|
|United States, Louisiana|
|Ochsner Clinic Foundation||Recruiting|
|New Orleans, Louisiana, United States, 70121|
|United States, New York|
|Weill Cornell Medicine||Recruiting|
|New York, New York, United States, 10021|
|United States, Washington|
|Fred Hutchinson Cancer Research Center||Recruiting|
|Seattle, Washington, United States, 98109|
|Study Chair:||Avinash Desai, MD||Actinium Pharmaceuticals, Inc.|