Acute Myeloid LeukemiaPhase 1/2NCT03867682
Venetoclax and Lintuzumab-Ac225 in AML Patients
A Phase 1/2 study testing Lintuzumab-Ac225, Venetoclax and Spironolactone in people with Acute Myeloid Leukemia and Relapsed Adult AML, run by Actinium Pharmaceuticals at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Relapsed Adult AML
- What is being tested?
- Lintuzumab-Ac225, Venetoclax and Spironolactone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 5 sitesUnited States
- Study dates
- 15 Jan 2020to Jun 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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
- ECOG ≤ 2
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- Estimated creatinine clearance ≥ 50 mL/min
- AST and ALT ≤ 3.0 x ULN
- Bilirubin ≤ 3.0 x ULN
Who cannot join
- Active CNS Leukemia.
- Known HIV infection or known hepatitis B or hepatitis C infection (with a detectable viral load).
- Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
- Secondary refractory AML (e.g., treated for current relapse without achieving remission);
- With the exception that single agent FLT3 inhibitors, IDH1/IDH2 inhibitors are allowed for current relapse without achieving remission.
- Have received prior radiation to maximally tolerated levels to any critical normal organ.
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- 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 has GVHD or is still receiving immunosuppression/GVHD therapy).
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of California
Los Angeles, California, 90095
- Recruiting
University of Louisville
Louisville, Kentucky, 40202
- Recruiting
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
- Recruiting
Weill Cornell Medicine
New York, New York, 10021
- Recruiting
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
About this study
Official title: A Phase I/II Study of Venetoclax 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 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)
Read the 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.
- Conditions
- Acute Myeloid Leukemia, Relapsed Adult AML
- Being tested
- Lintuzumab-Ac225, Venetoclax, Spironolactone
- Keywords
- Lintuzumab-Ac225, Venetoclax, Lintuzumab, Refractory AML
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lintuzumab-Ac225Biological
Also called Actimab
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.
VenetoclaxDrug
Also called Venclexta
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.
SpironolactoneDrug
Also called Aldactone
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.
| Study group | Role | What they receive |
|---|---|---|
| Phase I and Phase II | Experimental | 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. Receives: Biological: Lintuzumab-Ac225; Drug: Venetoclax; Drug: Spironolactone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 6 months
Secondary outcomes (7)
Phase I: Overall Response
Number of patients who's overall response is CR, CRh, or CRi
Measured: Up to 6 months
Phase I and II: OS
Number of patients who died
Measured: End of 6 months, 12 months, 2 years
Phase I and II: DFS
Disease-free survival
Measured: 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
Measured: Through study completion, up to 2 years
Phase I and II: Evaluate BH3 priming assay results
Summary of assay results
Measured: Completion of Cycle 1, estimated 1 month
Phase I and II: MRD status
Number of patients who are MRD negative
Measured: 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
Measured: Through study completion, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2019
- Study start15 Jan 2020
- Primary completionNov 2023 (estimated)
- Study completionJun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Actinium Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Avinash Desai, MD, Study chair, Actinium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03867682
- Sponsor's protocol ID
- LIN-AC225-AML02
- Status last verified
- Aug 2023
- First submitted
- 6 Mar 2019
- Last updated
- 4 Aug 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Garg R, Allen KJH, Dawicki W, Geoghegan EM, Ludwig DL, Dadachova E. 225Ac-labeled CD33-targeting antibody reverses resistance to Bcl-2 inhibitor venetoclax in acute myeloid leukemia models. Cancer Med. 2021 Feb;10(3):1128-1140. doi: 10.1002/cam4.3665. Epub 2020 Dec 21.
PubMed 33347715
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Venetoclax and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML
- ClinicalTrials.gov ID
- NCT03867682
- Acronym / sponsor ID
- LIN-AC225-AML02
- Conditions
- Acute Myeloid Leukemia, Relapsed Adult AML
- Keywords
- Lintuzumab-Ac225, Venetoclax, Lintuzumab, Refractory AML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Actinium PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 15 Jan 2020 (actual)
- Primary completion
- Nov 2023 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 8 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I and Phase II | Experimental | Biological: Lintuzumab-Ac225, Drug: Venetoclax, Drug: SpironolactoneLintuzumab-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Refractory or relapsed AML which will include:
- 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
- ECOG ≤ 2
- Estimated creatinine clearance ≥ 50 mL/min
- AST and ALT ≤ 3.0 x ULN
Key exclusion criteria (11 listed)
- Active CNS Leukemia.
- Known HIV infection or known hepatitis B or hepatitis C infection (with a detectable viral load).
- Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
- Secondary refractory AML (e.g., treated for current relapse without achieving remission);
- Have received prior radiation to maximally tolerated levels to any critical normal organ.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lintuzumab-Ac225Also: ActimabIn 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. | Biological | Phase I and Phase II |
| VenetoclaxAlso: Venclexta400 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. | Drug | Phase I and Phase II |
| SpironolactoneAlso: Aldactone25 mg by mouth daily, administered on Cycle 1 Day 15 and continued for 12 months after the subject's last treatment with lintuzumab-Ac225. | Drug | Phase I and Phase II |
Primary outcome
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.
7 secondary outcomes
Phase I: Overall Response
Time frame: Up to 6 months
Phase I and II: OS
Time frame: End of 6 months, 12 months, 2 years
Phase I and II: DFS
Time frame: End of 6 months, 12 months, 2 years
Phase I and II: Evaluate incidence of AEs and SAEs
Time frame: 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
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
Phase I and II: Lab abnormalities (other than hematologic indices)
Time frame: Through study completion, up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
- Derived from this study: PubMed 33347715Garg R, Allen KJH, Dawicki W, Geoghegan EM, Ludwig DL, Dadachova E. 225Ac-labeled CD33-targeting antibody reverses resistance to Bcl-2 inhibitor venetoclax in acute myeloid leukemia models. Cancer Med. 2021 Feb;10(3):1128-1140. doi: 10.1002/cam4.3665. Epub 2020 Dec 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Avinash Desai, MD study chair
Actinium Pharmaceuticals, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lintuzumab-Ac225, Venetoclax and Spironolactone in people with Acute Myeloid Leukemia and Relapsed Adult AML, run by Actinium Pharmaceuticals at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Actinium Pharmaceuticals, Inc. (+1-646-677-3878, actimab@actiniumpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225 (time frame: Cycle 1, up to 48 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03867682, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.