Combining Venetoclax and Lintuzumab-Ac225 for AML Treatment

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

This study is testing a new combination of two treatments, venetoclax and lintuzumab-Ac225, to see if it can help people with relapsed or hard-to-treat acute myeloid leukemia feel better.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Actinium Pharmaceuticals (industry)
• Drugs / interventions: radiation, lintuzumab
• Locations: 5 sites (Los Angeles, California and 4 other locations)
• Trial ID: NCT03867682 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label Phase I/II trial aims to evaluate the safety and efficacy of combining lintuzumab-Ac225 with venetoclax in patients with relapsed or refractory acute myeloid leukemia (AML). The Phase I portion focuses on determining the maximum tolerated dose (MTD) of lintuzumab-Ac225, while the Phase II portion assesses the overall response rates of patients treated at this MTD. Patients will be monitored for a minimum of four weeks before any dose escalation occurs, ensuring careful observation of treatment effects. The study specifically targets patients with CD33 positive AML who have not responded to previous therapies.

Who should consider this trial

Good fit: Ideal candidates for this study are adults with relapsed or refractory acute myeloid leukemia who have CD33 positive disease.

Not a fit: Patients with active CNS leukemia or those with known HIV or hepatitis infections may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with relapsed or refractory AML, potentially improving their response rates.

How similar studies have performed: While this approach is novel in combining these specific agents, similar studies have shown promise in targeting AML with innovative therapies.

Eligibility criteria

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).

Where this trial is running

Los Angeles, California and 4 other locations

• University of California — Los Angeles, California, United States (RECRUITING)
• University of Louisville — Louisville, Kentucky, United States (RECRUITING)
• Ochsner Clinic Foundation — New Orleans, Louisiana, United States (RECRUITING)
• Weill Cornell Medicine — New York, New York, United States (RECRUITING)
• Fred Hutchinson Cancer Research Center — Seattle, Washington, United States (RECRUITING)

Study contacts

• Study coordinator: Actinium Pharmaceuticals, Inc.

Conditions: Acute Myeloid Leukemia, Relapsed Adult AML, Lintuzumab-Ac225, Venetoclax, Lintuzumab, Refractory AML