Trial Outcomes & Findings for JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia (NCT NCT03557970)

Last Updated: 2021-12-02

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

first 2 cycles of study drug

Results posted on

2021-12-02

Participant Flow

Participants for this study were recruited from within the hematology and oncology practices participating research sites. There were 8 consented patients that were deemed screen failures and thus not enrolled on this trial. The reasons for screen failures were: patient chose alternative treatment (n=3), patient had insufficient sample for the ex vivo drug screen (n=3), patient was too sick to participate in the trial (n=1), and patient withdrew consent (n=1).

All enrolled participants were included in the study and assigned to 1 of 2 arms according to their ex vivo sensitivity to study drug. Consented patients with indeterminate ex vivo sensitivity were considered screen failures. Although this was designed as a 2-arm trial (for purposes of stopping early for futility at the end of stage 1 of the study and of correlating pre-treatment ex vivo sensitivity with post-treatment clinical response), the study drug regimen was identical in the 2 arms.

Participant milestones

Participant milestones
Measure	Assay Positive Participants with ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Sensitivity is defined as an IC50 that is \<=20% of the median IC50.	Assay Negative Participants lacking ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Lack of sensitivity is defined as an IC50 that is \>20% of the median IC50.
Overall Study STARTED	1	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Assay Positive Participants with ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Sensitivity is defined as an IC50 that is \<=20% of the median IC50.	Assay Negative Participants lacking ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Lack of sensitivity is defined as an IC50 that is \>20% of the median IC50.
Overall Study Study closure	1	0
Overall Study Physician Decision	0	1
Overall Study Death	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Assay Positive n=1 Participants Participants with ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Sensitivity is defined as an IC50 that is \<=20% of the median IC50.	Assay Negative n=2 Participants Participants lacking ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Lack of sensitivity is defined as an IC50 that is \>20% of the median IC50.	Total n=3 Participants Total of all reporting groups
Age, Continuous	72 years n=5 Participants	60 years n=7 Participants	63 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: first 2 cycles of study drug

Population: According to the protocol, only those participants who have completed at least 1 cycle of study agent and have response measurements will be evaluable for objective response. Since the only participant with a recorded disease response designation did not complete 1 cycle of study drug, there are no evaluable participants for this trial's primary outcome.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Assay Positive n=1 Participants Participants with ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Sensitivity is defined as an IC50 that is \<=20% of the median IC50.	Assay Negative n=2 Participants Participants lacking ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Lack of sensitivity is defined as an IC50 that is \>20% of the median IC50.
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 Treatment-related AE's (any grade)	0 Participants	0 Participants
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 Non-treatment-related AE's (any grade)	1 Participants	2 Participants

SECONDARY outcome

Timeframe: achievement of >=PR through end of study

Population: No participants achieved a response while on study so duration of response cannot be computed.

For participants that achieve at least a partial response (PR), the length of time between start date of this response and progression.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: study enrollment until last on-study disease assessment

Population: EFS cannot be calculated due to a lack of disease response information.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Assay Positive n=1 Participants Participants with ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Sensitivity is defined as an IC50 that is \<=20% of the median IC50.	Assay Negative n=2 Participants Participants lacking ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Lack of sensitivity is defined as an IC50 that is \>20% of the median IC50.
Overall Survival	NA months There were no observed deaths in this arm (i.e., the lone participant withdrew from study to transition to hospice) so median OS could not be computed.	6.6 months This arm's sample size of 2 participants (with 1 observed death) was insufficient for calculating a confidence interval for the median OS.

Adverse Events

Assay Positive

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Assay Negative

Serious events: 0 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Assay Positive n=1 participants at risk Participants with ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Sensitivity is defined as an IC50 that is \<=20% of the median IC50.	Assay Negative n=2 participants at risk Participants lacking ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Lack of sensitivity is defined as an IC50 that is \>20% of the median IC50.
Infections and infestations Catheter related infection	100.0% 1/1 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	0.00% 0/2 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."

Other adverse events

Other adverse events
Measure	Assay Positive n=1 participants at risk Participants with ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Sensitivity is defined as an IC50 that is \<=20% of the median IC50.	Assay Negative n=2 participants at risk Participants lacking ex vivo sensitivity to study drug according to a cell viability assay performed on participant bone marrow or peripheral blood cells. Lack of sensitivity is defined as an IC50 that is \>20% of the median IC50.
Gastrointestinal disorders Abdominal pain	100.0% 1/1 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	0.00% 0/2 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."
Musculoskeletal and connective tissue disorders Bone pain (worsening)	0.00% 0/1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	50.0% 1/2 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."
Gastrointestinal disorders Diarrhea	0.00% 0/1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	50.0% 1/2 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	50.0% 1/2 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."
Metabolism and nutrition disorders Hyperkalemia	100.0% 1/1 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	0.00% 0/2 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."
Gastrointestinal disorders Mucositis oral	0.00% 0/1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	50.0% 1/2 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."
Gastrointestinal disorders Nausea	100.0% 1/1 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	0.00% 0/2 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."
General disorders Pain in extremity	100.0% 1/1 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	0.00% 0/2 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."
Vascular disorders Thromboembolic event	100.0% 1/1 • Number of events 1 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."	0.00% 0/2 • Per protocol "from the time subject has started study drug to completion of the study.", with post- drug exposure on-study time periods of 12, 38, and 189 days (mean of 80 days) for the 3 enrolled participants Per protocol "Toxicities will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5)."

Additional Information

Elie Traer, MD PhD

Oregon Health and Science University

Phone: 5034943553

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place