Acute Myeloid Leukemia, Advanced Solid Tumors
Conditions
Keywords
Advanced solid tumors, Acute myeloid leukemia, gilteritinib, ASP2215
Brief summary
The purpose of the study was to provide access to continued treatment for those who participated in other Astellas sponsored ASP2215 trials that completed the primary analysis and, had the potential to continue to derive clinical benefit from the treatment with ASP2215, and who did not meet any of the study discontinuation criteria in the present study.
Interventions
DRUGGilteritinib
oral tablet
Sponsors
Astellas Pharma Global Development, Inc.
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject must currently be participating in an Astellas sponsored, single agent ASP2215 trial, receiving ASP2215 and have not met any discontinuation criteria of the parent study and can enroll into this rollover study without interruption of study drug, or with no more than 2 weeks interruption in study drug. * Subject must be deriving benefit from continued treatment without any persistent intolerable toxicity from continued treatment of ASP2215. * Female subject must either: * Be of non-childbearing potential: post-menopausal (defined as at least 1 year without any menses) prior to Screening, or documented surgically sterile or post-hysterectomy (at least 1 month prior to Screening) * Or, if of childbearing potential, Agree not to try to become pregnant during the study and for 180 days after the final study drug administration; And have a negative urine pregnancy test at Day 1; And, if heterosexually active, agree to consistently use two forms of highly effective birth control (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 180 days after the final study drug administration. * Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 60 days after the final study drug administration. * Female subject must not donate ova starting at Screening and throughout the study period, and for 180 days after the final study drug administration. * Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (at least one of which must be a barrier method) starting at Screening and continue throughout the study period, and for 120 days after the final study drug administration. * Male subject must not donate sperm starting at Screening and throughout the study period and, for 120 days after the final study drug administration. * Subject agrees not to participate in another interventional study while on treatment.
Exclusion criteria
* Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A. * Subject requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject. * Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P-glycoprotein (P-gp) with the exception of drugs that are considered absolutely essential for the care of the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 811.0 days, minimum of 43 days and maximum of 1067 days) | AE was defined as any untoward medical occurrence in a participant administered a study drug or has undergone study procedures and which did not necessarily have a causal relationship with this treatment. An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, Electrocardiography (ECG) data, and physical exam) was defined as an AE only if the abnormality induces clinical signs or symptoms or requires active intervention or requires interruption or discontinuation of study medication or the abnormality or investigational value is clinically significant in the opinion of the investigator. |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | EOT Visit (30 days post-last dose, maximum treatement duration of 1067 days) | ECOG performance status was used to assess participants disease progression, and ability to carry out the daily living activities. The participants were graded on a scale of 0 to 5 where 0 = fully active, able to carry on all predisease performance without restriction; 1 = restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = capable of only limited self-care,confined to bed or chair more than 50% of waking hours; 4 = completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5 = Dead. Number of participants with ECOG performance status was reported. |
Countries
United States
Participant flow
Recruitment details
Participants from previosuly conducted ASP2215 trial were recruited to receive gilteritinib at a dose specified at the time of their end of study visit in the previous ASP2215 study.
Pre-assignment details
Participants with Acute myeloid leukemia (AML) and advanced solid tumors who completed the protocol requirements of the previous ASP2215 trial (NCT02014558 and NCT02456883) were included in this study. 9 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Gilteritinib 40 mg Participants received gilteritinib 40 mg dose (one tablet of 40 mg) orally once a day in continuous 28-day cycles at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants no longer received clinical benefit from therapy, or unacceptable toxicity occurred, or met one of the treatment discontinuation criteria. | 2 |
| Gilteritinib 80 mg Participants received gilteritinib 80 mg dose (two tablets of 40 mg) orally once a day in continuous 28-day cycles at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants no longer received clinical benefit from therapy, or unacceptable toxicity occurred, or met one of the treatment discontinuation criteria. | 3 |
| Gilteritinib 120 mg Participants received gilteritinib 120 mg dose (three tablets of 40 mg) orally once a day in continuous 28-day cycles at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants no longer received clinical benefit from therapy, or unacceptable toxicity occurred, or met one of the treatment discontinuation criteria. | 3 |
| Gilteritinib 200 mg Participants received gilteritinib 200 mg dose (five tablets of 40 mg) orally once a day in continuous 28-day cycles at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants no longer received clinical benefit from therapy, or unacceptable toxicity occurred, or met one of the treatment discontinuation criteria. | 1 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Disease Progression | 0 | 1 | 0 | 0 |
| Overall Study | Participant Transitioned to Commercial Drug | 1 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 40 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 41 Years STANDARD_DEVIATION 17.5 | 55.7 Years STANDARD_DEVIATION 12.1 | 31.0 Years | 47.5 Years STANDARD_DEVIATION 17.7 | 46.2 Years STANDARD_DEVIATION 15 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 3 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 2 / 2 | 3 / 3 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 2 / 2 | 1 / 3 | 2 / 3 | 0 / 1 |
Outcome results
Primary
Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT)
ECOG performance status was used to assess participants disease progression, and ability to carry out the daily living activities. The participants were graded on a scale of 0 to 5 where 0 = fully active, able to carry on all predisease performance without restriction; 1 = restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = capable of only limited self-care,confined to bed or chair more than 50% of waking hours; 4 = completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5 = Dead. Number of participants with ECOG performance status was reported.
Time frame: EOT Visit (30 days post-last dose, maximum treatement duration of 1067 days)
Population: Participants in the SAF with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gilteritinib 40 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 4 | 0 Participants |
| Gilteritinib 40 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 5 | 0 Participants |
| Gilteritinib 40 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 0 | 2 Participants |
| Gilteritinib 40 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 1 | 0 Participants |
| Gilteritinib 40 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 2 | 0 Participants |
| Gilteritinib 40 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 3 | 0 Participants |
| Gilteritinib 80 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 3 | 0 Participants |
| Gilteritinib 80 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 1 | 3 Participants |
| Gilteritinib 80 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 4 | 0 Participants |
| Gilteritinib 80 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 0 | 0 Participants |
| Gilteritinib 80 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 5 | 0 Participants |
| Gilteritinib 80 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 2 | 0 Participants |
| Gilteritinib 120 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 5 | 0 Participants |
| Gilteritinib 120 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 0 | 0 Participants |
| Gilteritinib 120 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 1 | 0 Participants |
| Gilteritinib 120 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 3 | 0 Participants |
| Gilteritinib 120 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 2 | 1 Participants |
| Gilteritinib 120 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 4 | 0 Participants |
| Gilteritinib 200 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 2 | 0 Participants |
| Gilteritinib 200 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 3 | 0 Participants |
| Gilteritinib 200 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 5 | 0 Participants |
| Gilteritinib 200 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 1 | 1 Participants |
| Gilteritinib 200 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 4 | 0 Participants |
| Gilteritinib 200 mg | Eastern Cooperative Oncology Group (ECOG) Performance Status at End Of Treattment Visit (EOT) | Grade 0 | 0 Participants |
Primary
Number of Participants With Adverse Events
AE was defined as any untoward medical occurrence in a participant administered a study drug or has undergone study procedures and which did not necessarily have a causal relationship with this treatment. An abnormality identified during a medical test (e.g., laboratory parameter, vital sign, Electrocardiography (ECG) data, and physical exam) was defined as an AE only if the abnormality induces clinical signs or symptoms or requires active intervention or requires interruption or discontinuation of study medication or the abnormality or investigational value is clinically significant in the opinion of the investigator.
Time frame: From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 811.0 days, minimum of 43 days and maximum of 1067 days)
Population: Participants in the SAF were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gilteritinib 40 mg | Number of Participants With Adverse Events | 2 Participants |
| Gilteritinib 80 mg | Number of Participants With Adverse Events | 3 Participants |
| Gilteritinib 120 mg | Number of Participants With Adverse Events | 3 Participants |
| Gilteritinib 200 mg | Number of Participants With Adverse Events | 1 Participants |