Venetoclax and Lintuzumab-Ac225 in AML Patients

August 2, 2023 updated by: Actinium Pharmaceuticals

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.

  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)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

38

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • University Of Louisville
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Recruiting
        • Ochsner Clinic Foundation
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • Weill Cornell Medicine
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Refractory or relapsed AML which will include:

    1. Refractory disease will be defined as at least 1 prior treatment with no remission.
    2. Relapsed disease will be defined as 5% or more blasts in bone marrow seen after remission.
    3. Patients with AML arising from myelodysplastic syndromes (including CMML) or myeloproliferative neoplasms (secondary AML, ts-AML) are also eligible.
  2. 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
  3. ECOG ≤ 2
  4. Estimated creatinine clearance ≥ 50 mL/min
  5. AST and ALT ≤ 3.0 x ULN
  6. Bilirubin ≤ 3.0 x ULN

Exclusion Criteria:

  1. Active CNS Leukemia.
  2. Known HIV infection or known hepatitis B or hepatitis C infection (with a detectable viral load).
  3. Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.

  4. 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.

  5. Have received prior radiation to maximally tolerated levels to any critical normal organ.
  6. Clinically significant cardiac disease.
  7. Active, uncontrolled serious infection.
  8. Have other non-myeloid malignancy within 2 years of entry (with exceptions).
  9. Psychiatric disorder that would preclude study participation
  10. Previous solid organ transplant (prior treatment with SCT is allowed but not if patient has GVHD or is still receiving immunosuppression/GVHD therapy).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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 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.
Biological: Lintuzumab-Ac225
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:
  • Actimab
Drug: Venetoclax
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:
  • Venclexta
Drug: Spironolactone
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.
Other Names:
  • Aldactone

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 added to venetoclax for patients with CD33 positive relapse/refractory AML.
Cycle 1, up to 48 days
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.
Up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I: Overall Response
Time Frame: Up to 6 months
Number of patients who's overall response is CR, CRh, or CRi
Up to 6 months
Phase I and II: OS
Time Frame: End of 6 months, 12 months, 2 years
Number of patients who died
End of 6 months, 12 months, 2 years
Phase I and II: DFS
Time Frame: End of 6 months, 12 months, 2 years
Disease-free survival
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Actinium Pharmaceuticals

Investigators

  • Study Chair: Avinash Desai, MD, Actinium Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2020

Primary Completion (Estimated)

November 1, 2023

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

March 6, 2019

First Submitted That Met QC Criteria

March 6, 2019

First Posted (Actual)

March 8, 2019

Study Record Updates

Last Update Posted (Actual)

August 4, 2023

Last Update Submitted That Met QC Criteria

August 2, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LIN-AC225-AML02

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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