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Acute Myeloid LeukemiaPhase 1/2NCT03932318

Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients

A Phase 1/2 study testing Lintuzumab-Ac225, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia and Relapsed Adult AML, run by Actinium Pharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The study is a multicenter, open label Phase I/II trial. 1. 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) 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 Azacitidine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Mar 2023to Sep 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

  • 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;
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  • 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.

Who cannot join

  • 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.
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  • 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).

About this study

Official title: 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.

  1. 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)
  2. 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)
Read the 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.

Being tested
Lintuzumab-Ac225, Venetoclax, Azacitidine
Keywords
Lintuzumab-Ac225, Venetoclax, Azacitidine, 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.

  • AzacitidineDrug

    Also called Vidaza

    75 mg/m2 will be administered on days 1-7 of a 28-day cycle.

Study groups in NCT03932318
Study groupRoleWhat they receive
Phase I and Phase IIExperimentalLintuzumab-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.
Receives: Biological: Lintuzumab-Ac225; Drug: Venetoclax; Drug: Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225

    To determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 when given in combination with venetoclax and azacitidine for patients with CD33 positive AML

    Measured: Cycle 1, up to 48 days

  2. Phase II: Overall Response (CR + CRh + CRi + MLFS)

    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

    Measured: Up to 6 months

Secondary outcomes (8)

  1. Phase I: Overall Response

    Number of patients who's overall response is CR or CRh or CRi or MLFS

    Measured: Up to 6 months

  2. Phase I: OS

    Number of patients who died

    Measured: Phase I: End of 6 months, 12 months, 24 months.

  3. Phase II: OS

    Number of patients who died

    Measured: Phase II: End of 6 months, 12 months, 24 months

  4. Phase I and II: DFS

    Disease-free survival

    Measured: Through study completion, up to 2 years

  5. 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

  6. 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

  7. Phase I and II: Evaluate BH3 priming assay results

    Summary of assay results

    Measured: Completion of Cycle 1, estimated 1 month

  8. 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2019
  2. Study startMar 2023 (estimated)
  3. Primary completionDec 2023 (estimated)
  4. Study completionSep 2024 (estimated)

Why it stopped: study postponed

Resources

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03932318
Sponsor's protocol ID
LIN-AC225-AML03
Status last verified
Jul 2023
First submitted
17 Apr 2019
Last updated
20 Jul 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lintuzumab-Ac225, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia and Relapsed Adult AML, run by Actinium Pharmaceuticals.

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 12 inclusion and 9 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: withdrawn, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. 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 NCT03932318.

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 20 Jul 2023.

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