Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients
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|ClinicalTrials.gov Identifier: NCT03932318|
Recruitment Status : Not yet recruiting
First Posted : April 30, 2019
Last Update Posted : April 30, 2019
The study is a multicenter, open label Phase I/II trial.
- To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 when given in combination with venetoclax and azacitidine for patients with CD33 positive AML. (Phase I portion)
- To assess the percentage of patients with CR, CRh, CRi, MLFS or Overall Response (CR + CRh + CRi + MLFS), 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: Azacitidine||Phase 1 Phase 2|
|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 Azacitidine and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML|
|Estimated Study Start Date :||July 2019|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||January 2023|
Experimental: Phase I and Phase II
Lintuzumab-Ac225 will be administered on Day 8 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 will be taken on Days 1-21 of each cycle for up to 12 cycles.
Azacitidine will be administered on Days 1-7 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
75 mg/m2 will be administered on days 1-7 of a 28-day cycle.
Other Name: Vidaza
- 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 when given in combination with venetoclax and azacitidine for patients with CD33 positive AML
- Phase II: Overall Response (CR + CRh + CRi + MLFS) [ Time Frame: Up to 6 months ]To assess the percentage of patients achieving CR, CRh, CRi, morphologic leukemia-free state (MLFS), or Overall Response (CR + CRh + CRi + MLFS), 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 or CRh or CRi or MLFS
- Phase I: OS [ Time Frame: Phase I: End of 6 months, 12 months, 24 months. ]Number of patients who died
- Phase II: OS [ Time Frame: Phase II: End of 6 months, 12 months, 24 months ]Number of patients who died
- Phase I and II: DFS [ Time Frame: Through study completion, up to 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: Lab abnormalities (other than hematologic indices) [ Time Frame: Through study completion, up to 2 years ]Summary of rate of Grade 3/4 lab abnormalities
- 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
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): NCT03932318
|Contact: Actinium Pharmaceuticals, Inc.||+email@example.com|