Recurrent Acute Myeloid LeukemiaPhase 2NCT03557970
JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia
A Phase 2 study testing Edicotinib and Pharmacokinetic Study in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by OHSU Knight Cancer Institute at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- What is being tested?
- Edicotinib and Pharmacokinetic Study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Oct 2018to 28 Sep 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
OHSU Knight Cancer Institute
Portland, Oregon, 97239
About this study
Official title: A Phase 2 Open-Label Study of the CSF-1R Inhibitor JNJ-40346527 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
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.
Read the detailed description
PRIMARY OBJECTIVE:
Evaluate preliminary efficacy of JNJ-40346527 in participants with relapsed/refractory AML.
- 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.
- 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:
- 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.
- 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.
- Being tested
- Edicotinib, Pharmacokinetic Study
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EdicotinibDrug
Also called JNJ-40346527
Given PO
Pharmacokinetic StudyOther
Also called PHARMACOKINETIC, PK Study
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (JNJ-40346527) | Experimental | Participants receive JNJ-40346527 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Edicotinib; Other: Pharmacokinetic Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Objective Response Rate
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.
Measured: first 2 cycles of study drug
Secondary outcomes (4)
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
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.
Measured: 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
For participants that achieve at least a partial response (PR), the length of time between start date of this response and progression.
Measured: achievement of >=PR through end of study
Event-free Survival
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.
Measured: study enrollment until last on-study disease assessment
Overall Survival
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.
Measured: 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"
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2018
- Study start5 Oct 2018
- Primary completion28 Sep 2020
- Study completion28 Sep 2020
Why it stopped: Not enough enrollment to determine efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Oregon Health and Science University, Janssen, LP, The Leukemia and Lymphoma Society
- Responsible party
- Principal investigator, Elie Traer, MD PhD, OHSU Knight Cancer Institute
- Investigators
- Elie Traer, MD, Principal investigator, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03557970
- Sponsor's protocol ID
- STUDY00017583
- Other IDs
- NCI-2018-00869, STUDY00017583
- Status last verified
- Dec 2021
- First submitted
- 5 Jun 2018
- Last updated
- 2 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-Label Study of the CSF-1R Inhibitor JNJ-40346527 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT03557970
- Acronym / sponsor ID
- STUDY00017583
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not enough enrollment to determine efficacy
- Enrolment
- 3 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- Oregon Health and Science University, Janssen, LP, The Leukemia and Lymphoma Society
- Study start
- 5 Oct 2018 (actual)
- Primary completion
- 28 Sep 2020 (actual)
- Study completion
- 28 Sep 2020 (actual)
- First posted
- 15 Jun 2018 (actual)
- Results
- Posted 2 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
Evaluate preliminary efficacy of JNJ-40346527 in participants with relapsed/refractory AML.
- 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.
- 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:
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (JNJ-40346527) | Experimental | Drug: Edicotinib, Other: Pharmacokinetic StudyParticipants receive JNJ-40346527 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EdicotinibAlso: JNJ-40346527Given PO | Drug | Treatment (JNJ-40346527) |
| Pharmacokinetic StudyAlso: PHARMACOKINETIC, PK StudyCorrelative studies | Other | Treatment (JNJ-40346527) |
Primary outcome
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.
4 secondary outcomes
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
Duration of Response
Time frame: achievement of >=PR through end of study
Event-free Survival
Time frame: 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"
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elie Traer, MD principal investigator
OHSU Knight Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Edicotinib and Pharmacokinetic Study in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by OHSU Knight Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Objective Response Rate (time frame: first 2 cycles of study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2021.