NCT03867682

Brief Summary

The study is a multicenter, open label Phase I/II trial.

  1. 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. 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)

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
38

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2020

Longer than P75 for phase_1

Geographic Reach
1 country

5 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 6, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 8, 2019

Completed
10 months until next milestone

Study Start

First participant enrolled

January 15, 2020

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2023

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2024

Completed
Last Updated

August 4, 2023

Status Verified

August 1, 2023

Enrollment Period

3.8 years

First QC Date

March 6, 2019

Last Update Submit

August 2, 2023

Conditions

Acute Myeloid LeukemiaRelapsed Adult AML

Keywords

Lintuzumab-Ac225VenetoclaxLintuzumabRefractory AML

Outcome Measures

Primary Outcomes (2)

  • 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.

    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.

    Up to 6 months

Secondary Outcomes (7)

  • Phase I: Overall Response

    Up to 6 months

  • Phase I and II: OS

    End of 6 months, 12 months, 2 years

  • Phase I and II: DFS

    End of 6 months, 12 months, 2 years

  • Phase I and II: Evaluate incidence of AEs and SAEs

    Through study completion, up to 2 years

  • Phase I and II: Evaluate BH3 priming assay results

    Completion of Cycle 1, estimated 1 month

  • +2 more secondary outcomes

Study Arms (1)

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.

Biological: Lintuzumab-Ac225Drug: VenetoclaxDrug: Spironolactone

Interventions

Lintuzumab-Ac225BIOLOGICAL

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.

Also known as: Actimab
Phase I and Phase II
VenetoclaxDRUG

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.

Also known as: Venclexta
Phase I and Phase II
SpironolactoneDRUG

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.

Also known as: Aldactone
Phase I and Phase II

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • Estimated creatinine clearance ≥ 50 mL/min
  • AST and ALT ≤ 3.0 x ULN
  • Bilirubin ≤ 3.0 x ULN

You may not qualify if:

  • 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);
  • a. 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.
  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

University of California

Los Angeles, California, 90095, United States

RECRUITING

University of Louisville

Louisville, Kentucky, 40202, United States

RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

RECRUITING

Weill Cornell Medicine

New York, New York, 10021, United States

RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (1)

  • 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.

    PMID: 33347715DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclaxSpironolactone

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

LactonesOrganic ChemicalsPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Avinash Desai, MD

    Actinium Pharmaceuticals, Inc.

    STUDY CHAIR

Central Study Contacts

Actinium Pharmaceuticals, Inc.

CONTACT

+1-646-677-3878actimab@actiniumpharma.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 6, 2019

First Posted

March 8, 2019

Study Start

January 15, 2020

Primary Completion

November 1, 2023

Study Completion

June 1, 2024

Last Updated

August 4, 2023

Record last verified: 2023-08

Locations

US(5)