- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03932318
Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients
A Phase I/II Study of Venetoclax and Azacitidine and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML
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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The study is a multicenter, open label Phase I and Phase II trial combining lintuzumab-Ac225 with venetoclax and azacitidine 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 each dose level will be observed for a minimum of 4 weeks before dose escalation occurs. There is no dose escalation for any individual patient. Lintuzumab-Ac225 is administered on Day 8 of the first 4 treatment cycles.
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
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Actinium Pharmaceuticals, Inc.
- Phone Number: +1-646-677-3878
- Email: actimab@actiniumpharma.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically confirmed acute myeloid leukemia
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.
White blood cell (WBC) count < 10 x 109/L;
a. Use of hydroxyurea, prior to Cycle 1 and during Cycles 1 and 2, is permitted to lower the WBC count in the peripheral blood.
- Age > 18 years.
- Estimated creatinine clearance ≥ 50 mL/min calculated by the Cockroft-Gault formula.
- AST and ALT ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).
- Bilirubin ≤ 3.0 x ULN (unless considered to be due to leukemic organ involvement).
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
Exclusion Criteria:
- Have acute promyelocytic leukemia (APL).
- Active CNS leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache.
- Have received prior radiation to maximally tolerated levels to any critical normal organ.
- Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
- Clinically significant cardiac disease.
- Active, uncontrolled serious infection.
- Have other non-myeloid malignancy within 2 years of entry (with exceptions).
- Psychiatric disorder that would preclude study participation
- Previous solid organ transplant (prior treatment with SCT is allowed but not if patient as GVHD or is still receiving immunosuppression/GVHD therapy).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 Names:
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 Names:
75 mg/m2 will be administered on days 1-7 of a 28-day cycle.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Cycle 1, up to 48 days
|
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
|
Up to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Through study completion, up to 2 years
|
Phase I and II: Evaluate BH3 priming assay results
Time Frame: Completion of Cycle 1, estimated 1 month
|
Summary of assay results
|
Completion of Cycle 1, estimated 1 month
|
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
|
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)
Time Frame: Through study completion, up to 2 years
|
Summary of rate of Grade 3/4 lab abnormalities
|
Through study completion, up to 2 years
|
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
|
Up to 6 months
|
Phase I: OS
Time Frame: Phase I: End of 6 months, 12 months, 24 months.
|
Number of patients who died
|
Phase I: End of 6 months, 12 months, 24 months.
|
Phase II: OS
Time Frame: Phase II: End of 6 months, 12 months, 24 months
|
Number of patients who died
|
Phase II: End of 6 months, 12 months, 24 months
|
Phase I and II: DFS
Time Frame: Through study completion, up to 2 years
|
Disease-free survival
|
Through study completion, up to 2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Avinash Desai, MD, Actinium Pharmaceuticals, Inc.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LIN-AC225-AML03
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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