Venetoclax and Lintuzumab-Ac225 in AML Patients

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase I/II Study of Venetoclax and Lintuzumab-Ac225 in Patients With Refractory or Relapsed AML

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03867682
• Other study ID #: LIN-AC225-AML02
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 15, 2020
• Est. completion date: June 2024

Study information

• Verified date: August 2023
• Source: Actinium Pharmaceuticals
• Contact: Actinium Pharmaceuticals, Inc.
• Phone: +1-646-677-3878
• Email: actimab[@]actiniumpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: June 2024
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Relapsed Adult AML

Intervention

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.

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.
• 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.

Locations

Country	Name	City	State
United States	University of California	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Weill Cornell Medicine	New York	New York
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Actinium Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Phase I: Overall Response	Number of patients who's overall response is CR, CRh, or CRi	Up to 6 months
Secondary	Phase I and II: OS	Number of patients who died	End of 6 months, 12 months, 2 years
Secondary	Phase I and II: DFS	Disease-free survival	End of 6 months, 12 months, 2 years
Secondary	Phase I and II: Evaluate incidence of AEs and SAEs	Rate of AEs and SAEs, including infusion-related reactions	Through study completion, up to 2 years
Secondary	Phase I and II: Evaluate BH3 priming assay results	Summary of assay results	Completion of Cycle 1, estimated 1 month
Secondary	Phase I and II: MRD status	Number of patients who are MRD negative	From date of first dose until the date of first documented response, first assessment at 6 months
Secondary	Phase I and II: Lab abnormalities (other than hematologic indices)	Summary of rate of Grade 3/4 lab abnormalities	Through study completion, up to 2 years