- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03557970
JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia
A Phase 2 Open-Label Study of the CSF-1R Inhibitor JNJ-40346527 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
Study Overview
Status
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Oregon
-
Portland, Oregon, United States, 97239
- OHSU Knight Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 1. Ability to understand and the willingness to sign a written informed consent document.
- 2. Age >= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included.
- 3. Morphologically documented relapsed/refractory AML as defined by World Health Organization (WHO) criteria after at least 1 prior therapy for AML with the exception of hydroxyurea, and not felt to have curative treatment options per treating physician, or the patients themselves are unwilling to consider curative treatment options.
- 4. Sufficient and viable bone marrow aspirate or peripheral blood collection to use for the ex vivo sensitivity assay.
- 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- 6. Women must not be pregnant or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to start of study drug administration.
- 7. Participants must agree to use an adequate method contraception.
- 8. Must be able to take oral medications.
9. Adequate organ function as defined by the following:
- Serum creatinine =< 2 x the upper limit of normal (ULN), or glomerular filtration rate > 20 ml/min as calculated by Cockcroft-Gault formula.
- Serum potassium, magnesium, and calcium (corrected for albumin) within institutional normal limits or can be corrected with supplementation.
- Total serum bilirubin =< 2.5 x ULN.
- Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =< 2.5 x ULN.
Exclusion Criteria:
- 1. Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype).
- 2. Active central nervous system involvement with AML.
- 3. Concurrent active malignancy with expected survival of less than 1 year. For example, candidates with treated skin cancers, prostate cancer, breast cancer, etc. without metastatic disease are candidates for therapy since their expected survival exceeds that of relapsed or refractory AML. All subjects with concurrent malignancies will be reviewed by the principal investigator (PI) prior to enrollment.
- 4. Clinically significant graft versus host disease (GVHD) or active GVHD requiring initiation or escalation of treatment within 28-day screening period.
- 5. Clinically significant coagulation abnormality, such as disseminated intravascular coagulation.
- 6. Participants who are currently receiving any other investigational agents.
- 7. Previous treatment with CSF-1R kinase inhibitor or CSF-1R blocking antibody.
- 8. Known clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis.
- 9. Untreated HIV or active hepatitis C detectable by polymerase chain reaction (PCR), or chronic hepatitis B (patients positive for hepatitis B core antibody who are receiving intravenous immunoglobulin (IVIG) are eligible if hepatitis B [HepB] polymerase chain reaction [PCR] is negative).
- 10. Known history of cerebrovascular accident, myocardial infarction, or intracranial hemorrhage within 2 months of enrollment.
- 11. Clinically significant surgery within 2 weeks of enrollment.
- 12. Per PI discretion, active infection that is not well controlled by antibacterial or antiviral therapy.
- 13. Cancer-directed therapy within 2 weeks prior to starting treatment, with the exception of hydroxyurea, which is allowed to control white blood cell count. Hydroxyurea will be weaned as soon as clinically feasible.
- 14. Unwillingness to receive infusion of blood products.
- 15. Drugs that affect the CYP3A4 systems are allowed and essential for cancer patients, including anti-fungals but should be used with caution.
- 16. Patients with uncontrolled white blood cell count (defined as > 50 K/cu mm not controlled with hydrea).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Correlative studies
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best Objective Response Rate
Time Frame: first 2 cycles of study drug
|
An objective response is defined as achievement of a PR or any type of CR (CR, CRm, CRc, CRi) during a participant's first 2 cycles of study drug.
Each participant's best disease response designation (amended from the IWG criteria specified by Cheson, 2003 JCO) during the first 2 cycles will be used when computing the best objective response rate.
This rate will be reported alongside an exact confidence interval for each arm separately.
|
first 2 cycles of study drug
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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: Start of study drug until 30 days after the last dose of study drug (while the participant remains on-study), which amounted to an average of 31 days for the 3 enrolled participants
|
The overall incidence of treatment-related and non-treatment-related toxicity (including serious and non-serious AEs).
See the Adverse Event module of the Results section for a tabular summary of each toxicity event and associated system organ class.
|
Start of study drug until 30 days after the last dose of study drug (while the participant remains on-study), which amounted to an average of 31 days for the 3 enrolled participants
|
Duration of Response
Time Frame: achievement of >=PR through end of study
|
For participants that achieve at least a partial response (PR), the length of time between start date of this response and progression.
|
achievement of >=PR through end of study
|
Event-free Survival
Time Frame: study enrollment until last on-study disease assessment
|
Defined for all patients of a trial; measured from the date of entry into a study to the date of relapse from PR or CR or CRi, progression, or death from any cause; patients not known to have any of these events are censored on the date they were last examined.
The Kaplan-Meier method will be used to estimate event-free survival.
|
study enrollment until last on-study disease assessment
|
Overall Survival
Time Frame: From study enrollment until end of participant follow-up (i.e., death or last contact), with the protocol specifying that "[p]articipants will be followed … until death"
|
Defined for all patients of a trial; measured from the date of entry into a study to the date of death from any cause; patients not known to have died at end of study are censored on the date they were last known to be alive.
The Kaplan-Meier method will be used to estimate overall survival.
|
From study enrollment until end of participant follow-up (i.e., death or last contact), with the protocol specifying that "[p]articipants will be followed … until death"
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Elie Traer, MD, OHSU Knight Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY00017583 (Other Identifier: OHSU Knight Cancer Institute)
- NCI-2018-00869 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Acute Myeloid Leukemia
-
Sumithira VasuCompletedRecurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes | Recurrent Adult Acute Myeloid Leukemia | Recurrent Childhood Acute Myeloid Leukemia | Minimal Residual DiseaseUnited States
-
National Cancer Institute (NCI)WithdrawnRecurrent Adult Acute Myeloid Leukemia | Recurrent Childhood Acute Myeloid Leukemia | CNS 2a | CNS 2b | CNS 2c | CNS1
-
National Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) | Adult Acute Myeloid Leukemia in Remission | Childhood Acute Myeloid Leukemia in Remission | Recurrent... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)TerminatedAcute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
Thomas Jefferson UniversityRecruitingRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
Affiliated Hospital to Academy of Military Medical...Beijing JD Biotech Co. LTD.RecruitingAcute Myeloid Leukemia Refractory | Acute Myeloid Leukemia RecurrentChina
-
Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
National Cancer Institute (NCI)WithdrawnRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia
Clinical Trials on Pharmacokinetic Study
-
M.D. Anderson Cancer CenterCompletedMetastatic Carcinoma in the Adrenal Cortex | Stage III Adrenal Cortex Carcinoma AJCC v8 | Stage IV Adrenal Cortex Carcinoma AJCC v8 | Unresectable Adrenal Cortex CarcinomaUnited States
-
National Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Refractory Malignant Solid Neoplasm | Recurrent Ewing Sarcoma | Recurrent Hepatoblastoma | Recurrent Histiocytic and Dendritic Cell Neoplasm | Recurrent Langerhans Cell Histiocytosis | Recurrent Malignant Germ Cell Tumor | Recurrent Malignant Solid Neoplasm | Recurrent... and other conditionsUnited States, Puerto Rico
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedAnatomic Stage III Breast Cancer AJCC v8 | Anatomic Stage IIIA Breast Cancer AJCC v8 | Anatomic Stage IIIB Breast Cancer AJCC v8 | Anatomic Stage IIIC Breast Cancer AJCC v8 | Prognostic Stage III Breast Cancer AJCC v8 | Prognostic Stage IIIA Breast Cancer AJCC v8 | Prognostic Stage IIIB Breast... and other conditionsUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)WithdrawnRecurrent Bladder Carcinoma | Bladder Cancer Stage 0 | Bladder Cancer Stage IUnited States
-
Seoul National University HospitalCompleted
-
Chiang Mai UniversityThailand Research FundUnknownPharmacokinetics | Efavirenz | PenicilliosisThailand
-
Rabin Medical CenterCompletedCongenital Cytomegalovirus InfectionIsrael
-
ISA PharmaceuticalsRegeneron PharmaceuticalsActive, not recruitingSquamous Cell Carcinoma of the Oropharynx | HPV16 PositiveNetherlands, United States, United Kingdom, France, Belgium, Czechia, Spain, Italy, Germany, Brazil, Hungary, Mexico, Poland
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingRecurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Recurrent Small Lymphocytic Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Refractory Chronic Lymphocytic Leukemia | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Richter Syndrome and other conditionsUnited States
-
Eben RosenthalRecruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Lung Carcinoma | Metastatic Malignant Neoplasm in the LungUnited States