JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia

Refractory Acute Myeloid Leukemia Clinical Trial

Official title: A Phase 2 Open-Label Study of the CSF-1R Inhibitor JNJ-40346527 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)

Status Terminated

Clinical Trial Summary

This phase II trial studies how well edicotinib (JNJ-40346527) works in treating participants with acute myeloid leukemia that has come back or does not respond to treatment. JNJ-40346527 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Clinical Trial Description

PRIMARY OBJECTIVE:

Evaluate preliminary efficacy of JNJ-40346527 in participants with relapsed/refractory AML.

I. Best objective response rate (> PR).

SECONDARY OBJECTIVES:

Assess safety and survival associated with JNJ-40346527 to treat participants with relapsed/refractory AML. Assess the duration of disease response associated with JNJ-40346527.

I. Overall incidence of treatment-related and non-treatment related toxicity. II. Duration of response. III. 12-month event-free survival. IV. 12-month overall survival.

EXPLORATORY OBJECTIVES:

I. Evaluate the pharmacokinetics of JNJ-40346527 and effective inhibition of CSF-1R in marrow aspirates using plasma inhibitory assays, with established CSF-1R-sensitive cell lines.

II. Identify the effect of JNJ-40346527 on leukemia cells and the immune microenvironment.

III. Identify and quantify the specific subpopulation of cells that express CSF-1R in participants and correlate these with clinical response to JNJ-40346527.

IV. Analyze the frequency of mutations using genomic deoxyribonucleic acid (DNA) from leukemia participants to determine if there is a genetic signature that predicts response to JNJ-40346527.

V. Using ribonucleic acid (RNA) sequencing (RNAseq), identify an expression signature in CSF-1R+ cells that predicts patient response.

VI. Evaluate the effect of JNJ-40346527 on immune cell populations (cytotoxic T cells, etc.) and phospho-signaling proteins by mass cytometry (CyTOF) analysis in pre- and post-treatment samples in order to identify biomarkers that predict patient response and prioritize potential combination strategies for future clinical trials.

VII. Determine how leukemia cells change in response to CSF-1R inhibition by assessing cells collected pre- and post-treatment using an ex vivo sensitivity to a panel of small molecule inhibitors to determine what new drug sensitivities may emerge in AML cells after CSF-1R inhibition.

OUTLINE:

Participants receive JNJ-40346527 orally (PO) twice a day (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up within 2 weeks, at 4-6 weeks until death or minimum of 12 months. ;

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

• NCT number: NCT03557970
• Study type: Interventional
• Source: OHSU Knight Cancer Institute
• Status: Terminated
• Phase: Phase 2
• Start date: October 5, 2018
• Completion date: September 28, 2020