JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT03557970|
Recruitment Status : Active, not recruiting
First Posted : June 15, 2018
Last Update Posted : June 26, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia||Drug: Edicotinib Other: Pharmacokinetic Study||Phase 2|
Evaluate preliminary efficacy of JNJ-40346527 in participants with relapsed/refractory AML.
I. 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.
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Open-Label Study of the CSF-1R Inhibitor JNJ-40346527 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)|
|Actual Study Start Date :||October 5, 2018|
|Estimated Primary Completion Date :||December 20, 2022|
|Estimated Study Completion Date :||December 30, 2023|
Experimental: Treatment (JNJ-40346527)
Participants receive JNJ-40346527 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Name: JNJ-40346527
Other: Pharmacokinetic Study
- Best objective response rate [ Time Frame: Up to 84 days ]A Simon 2-stage minimax design will be used to determine best objective response. The best objective response and exact confidence interval will be determined using the binomial distribution for each arm separately. Response assessment will be based on best objective response rates within the first 2 cycles of study drug, including complete response (CR), CR with inadequate bone marrow recovery, partial response, stable disease, or progressive disease.
- Incidence of treatment-related and non-treatment related adverse events per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 30 days after last dose of study drug ]The overall incidence of treatment-related and non-treatment related toxicity and the exact confidence interval will be estimated. In addition, each toxicity event will be tabulated and summarized by severity and major organ site.
- Duration of response [ Time Frame: Up to 12 months ]For participants that achieve > partial response (PR), how long do they maintain this response before progression?
- Event-free survival [ Time Frame: At 12 months ]Time-to-event analysis (e.g., Kaplan-Meier and cumulative incidence curves) will be used to evaluate event-free survival.
- Overall survival [ Time Frame: Up to Death (or date of last contact) ]Time-to-event analysis (e.g., Kaplan-Meier and cumulative incidence curves) will be used to evaluate overall survival.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03557970
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||Elie Traer, MD||OHSU Knight Cancer Institute|