Venetoclax and Lintuzumab-Ac225 in AML Patients

NCT ID: NCT03867682

Last Updated: 2023-08-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-15

Study Completion Date

2024-06-30

Brief Summary

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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)

Detailed Description

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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

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Acute Myeloid Leukemia Relapsed Adult AML

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Lintuzumab-Ac225

Intervention Type BIOLOGICAL

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.

Venetoclax

Intervention Type DRUG

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.

Spironolactone

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type BIOLOGICAL

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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Actimab Venclexta Aldactone

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Actinium Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Avinash Desai, MD

Role: STUDY_CHAIR

Actinium Pharmaceuticals, Inc.

Locations

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University of California

Los Angeles, California, United States

Site Status RECRUITING

University of Louisville

Louisville, Kentucky, United States

Site Status RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status RECRUITING

Weill Cornell Medicine

New York, New York, United States

Site Status RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Actinium Pharmaceuticals, Inc.

Role: CONTACT

+1-646-677-3878

References

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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.

Reference Type DERIVED
PMID: 33347715 (View on PubMed)

Other Identifiers

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LIN-AC225-AML02

Identifier Type: -

Identifier Source: org_study_id

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