Venetoclax and Lintuzumab-Ac225 in AML Patients

Actinium Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Relapsed Adult AML; Acute Myeloid Leukemia

Treatments: Drug: Venetoclax; Biological: Lintuzumab-Ac225; Drug: Spironolactone

Study type: Interventional

Funder types: Industry

Identifiers

NCT03867682

LIN-AC225-AML02

Details and patient eligibility

About

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)

Full 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.

Enrollment: 38 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

38 participants in 1 patient group

Phase I and Phase II

Experimental group

Description:

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.

Treatment:

Drug: Spironolactone

Biological: Lintuzumab-Ac225

Drug: Venetoclax