Venetoclax and Lintuzumab-Ac225 in AML Patients
- Conditions
- Acute Myeloid LeukemiaRelapsed Adult AML
- Interventions
- Registration Number
- NCT03867682
- Lead Sponsor
- Actinium Pharmaceuticals
- Brief Summary
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)
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 38
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Refractory or relapsed AML which will include:
- Refractory disease will be defined as at least 1 prior treatment with no remission.
- Relapsed disease will be defined as 5% or more blasts in bone marrow seen after remission.
- Patients with AML arising from myelodysplastic syndromes (including CMML) or myeloproliferative neoplasms (secondary AML, ts-AML) are also eligible.
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Circulating blast count ≤ 200/μL within 10 days prior to first cycle of treatment. Hydroxyurea should be used to keep the peripheral blast count ≤ 200/μL until the first day of protocol treatment, to the extent that this is possible
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ECOG ≤ 2
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Estimated creatinine clearance ≥ 50 mL/min
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AST and ALT ≤ 3.0 x ULN
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Bilirubin ≤ 3.0 x ULN
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Active CNS Leukemia.
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Known HIV infection or known hepatitis B or hepatitis C infection (with a detectable viral load).
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Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
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Secondary refractory AML (e.g., treated for current relapse without achieving remission);
a. With the exception that single agent FLT3 inhibitors, IDH1/IDH2 inhibitors are allowed for current relapse without achieving remission.
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Have received prior radiation to maximally tolerated levels to any critical normal organ.
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Clinically significant cardiac disease.
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Active, uncontrolled serious infection.
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Have other non-myeloid malignancy within 2 years of entry (with exceptions).
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Psychiatric disorder that would preclude study participation
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Previous solid organ transplant (prior treatment with SCT is allowed but not if patient has GVHD or is still receiving immunosuppression/GVHD therapy).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase I and Phase II Lintuzumab-Ac225 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. Phase I and Phase II Venetoclax 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. Phase I and Phase II Spironolactone 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.
- Primary Outcome Measures
Name Time Method Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225 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) 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.
- Secondary Outcome Measures
Name Time Method Phase I and II: Evaluate incidence of AEs and SAEs Through study completion, up to 2 years Rate of AEs and SAEs, including infusion-related reactions
Phase I: Overall Response Up to 6 months Number of patients who's overall response is CR, CRh, or CRi
Phase I and II: OS End of 6 months, 12 months, 2 years Number of patients who died
Phase I and II: DFS End of 6 months, 12 months, 2 years Disease-free survival
Phase I and II: Evaluate BH3 priming assay results Completion of Cycle 1, estimated 1 month Summary of assay results
Phase I and II: MRD status 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) Through study completion, up to 2 years Summary of rate of Grade 3/4 lab abnormalities
Trial Locations
- Locations (5)
University of California
🇺🇸Los Angeles, California, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States