NCT03705858

Actinium-225-Lintuzumab in Patients With Acute Myeloid Leukemia

Postremission Therapy With Actinium-225 (225Ac)-Lintuzumab (Actimab-A®) in Patients With Acute Myeloid Leukemia

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Joseph Jurcic · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to see what dose of 225Ac-lintuzumab is safest to give to acute myeloid leukemia (AML) patients who are in remission but still have minimal residual disease (MRD). About 12 subjects will be asked to take part in this phase 1, 3+3 dose-escalation study. In addition to confirming the safety profile of postremission therapy with 225Ac-lintuzumab, preliminary evidence of efficacy will be assessed by estimating progression-free survival (PFS) and overall survival (OS), and serially evaluating for MRD using cytogenetics, fluorescence in situ hybridization (FISH), or flow cytometric assays, as applicable.

Detailed description

Therapy with α particle-emitting constructs of the anti-CD33 monoclonal antibody lintuzumab has demonstrated significant tumor effects in AML. Because therapy is selectively targeted to leukemic blasts, it has the potential advantage of less extramedullary toxicity than conventional systemic agents. Moreover, the unique radiobiological features of α particle emissions may permit more efficient tumor cell kill with greater specificity than treatment with β particle-emitting radioisotopes. Objective responses in AML following treatment with 225Ac-lintuzumab have been seen in cytoreduced disease, either following chemotherapy or using a fractionated dosing scheme. The presence of MRD detectable by cytogenetic techniques and flow cytometric assays indicates a high risk of relapse for AML patients, despite achieving a clinical complete remission. The high linear energy and short range of α emissions make them ideally suited to eradicate MRD, as suggested by the clinical responses observed in earlier studies. To date, 225Ac-lintuzumab has only been studied in patients with overt leukemia. The aim of this phase 1 study is to identify the maximum tolerated dose (MTD) of 225Ac-lintuzumab that can be given safely to AML patients in the postremission setting in order to eliminate detectable MRD and ultimately prolong PFS and OS.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Ac-Lintuzumab	225Ac-lintuzumab will administered at 4 dose levels: 0.25, 0.5, 0.75 or 1 µCi/kg intravenously (IV) over 30 ± 10 minutes. The starting dose will be 0.5 µCi/kg. A dose of 0.25 µCi/kg will be studied only if 0.5 µCi/kg is determined to exceed the MTD. The lintuzumab dose will be adjusted to maintain a specific activity of 0.16 µCi/µg

Timeline

• Start date: 2019-02-28
• Primary completion: 2019-02-28
• Completion: 2019-02-28
• First posted: 2018-10-15
• Last updated: 2019-03-08

Regulatory

• FDA-regulated drug study