CSF1R Inhibitor JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia

2018-06-20 02:25:11 | BioPortfolio


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



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

1. Best objective response rate (>PR).


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.

1. Overall incidence of treatment-related and non-treatment related toxicity.

2. Duration of response.

3. 12-month event-free survival.

4. 12-month overall survival.


1. 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.

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

3. 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.

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

5. 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.

6. 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.


Participants receive FMS inhibitor JNJ-40346527 orally (PO) twice a day (BID) on days 1-28. Courses 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.

Study Design


Recurrent Adult Acute Myeloid Leukemia


FMS Inhibitor JNJ-40346527, Pharmacokinetic Study


OHSU Knight Cancer Institute
United States


Not yet recruiting


OHSU Knight Cancer Institute

Results (where available)

View Results


Published on BioPortfolio: 2018-06-20T02:25:11-0400

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Medical and Biotech [MESH] Definitions

A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin.

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A rare acute myeloid leukemia characterized by abnormal EOSINOPHILS in the bone marrow.

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