NCT03441048

Lintuzumab-Ac225 in Combination with Cladribine + Cytarabine + Filgastrim + Mitoxantrone (CLAG-M) for Relapsed/Refractory Acute Myeloid Leukemia

A Phase I Study of Lintuzumab-Ac225 in Combination with CLAG-M Chemotherapy in Patients with Relapsed/Refractory Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, single-center phase I clinical study aimed at determining the maximum-tolerated dose, recommended phase 2 dose and safety of Lintuzumab-Ac225 in combination with CLAG-M chemotherapy in the management of relapsed/refractory acute myeloid leukemia. This study uses a 3+3 design with a five-patient cohort at the recommended phase 2 dose.

Detailed description

Relapsed/refractory acute myeloid leukemia (RR-AML) in adults is an important therapeutic challenge. Nearly 60% of AML patients ultimately relapse or have refractory disease, and failure to achieve remission in this population is almost universally fatal. Therefore, a critical need exists for the development of novel therapies. Currently, for RR-AML, many institutions utilize the chemotherapy regimen of CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone) based on a reported morphological complete remission (CR) rate of 58% in prospective clinical trials. Because of this, and its favorable performance when compared with outcomes reported for other regimens utilized in RR-AML, we believe enhancing the efficacy of CLAG-M is a rational approach to improve therapy in RR-AML. A promising approach that could enhance the clearance of leukemic blasts when added to CLAG-M chemotherapy is a monoclonal antibody radioconjugate directed against markers expressed in leukemic cells. Radiation has known cytotoxic properties in chemo-resistant AML. The benefit of an antibody radioconjugate would be leukemic specific delivery of potent radiotherapy with potentially minimal systemic off-target side-effects. One such antibody radioconjugate is Lintuzumab-Ac225, a highly cytotoxic alpha radiation emitter that targets the cluster of differentiation 33 (CD33) cell surface antigen, which is expressed on leukemic cells. In this novel study, we aim to add the radioconjugated antibody Lintuzumab-Ac225 to salvage CLAG-M chemotherapy in order to improve the treatment response for patients with RR-AML.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Lintuzumab-Ac-225	Lintuzumab-Ac225 is an immunoconjugate \[antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)\] for the treatment of relapsed/refractory acute myeloid leukemia.
DRUG	Cladribine	Cladribine is a purine antimetabolite.
DRUG	Cytarabine	Cytarabine is an antineoplastic anti-metabolite.
DRUG	Mitoxantrone	Mitoxantrone is an anthracenedione antineoplastic agent.
DRUG	G-CSF	G-CSF is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells.

Timeline

• Start date: 2018-05-22
• Primary completion: 2024-05-22
• Completion: 2024-05-22
• First posted: 2018-02-22
• Last updated: 2024-10-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study