Trial Outcomes & Findings for Phase II Trial of Alisertib With Induction Chemotherapy in High-risk AML (NCT NCT02560025)

Last Updated: 2020-05-05

Results Overview

The number of participants that achieved a best overall response of complete remission while on study. Complete remission (CR): Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, existing extramedullary disease. If possible, at least one bone marrow biopsy should be performed to confirm CR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

From the start of treatment until the end of study treatment, up to approximately 10 months

Results posted on

2020-05-05

Participant Flow

Participant milestones

Participant milestones
Measure	Alisertib / MLN8237 Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Overall Study STARTED	42
Overall Study COMPLETED	39
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Alisertib / MLN8237 Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Overall Study Ineligible after consent/ registration	3

Baseline Characteristics

Phase II Trial of Alisertib With Induction Chemotherapy in High-risk AML

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alisertib / MLN8237 n=39 Participants Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Age, Continuous	67 years n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	39 Participants n=5 Participants
Cytogenetic Risk High	13 Participants n=5 Participants
Cytogenetic Risk Intermediate	26 Participants n=5 Participants
Median White Blood Cell (WBC) Count	3.2 Thousand WBC/ microliter blood n=5 Participants

PRIMARY outcome

Timeframe: From the start of treatment until the end of study treatment, up to approximately 10 months

Population: The three participants found to be ineligible after enrollment were excluded from the analysis

Outcome measures

Outcome measures
Measure	Alisertib / MLN8237 n=39 Participants Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Number of Participants That Achieved Complete Remission	20 Participants

PRIMARY outcome

Timeframe: From the start of treatment until the end of study treatment, up to approximately 10 months

Population: The three participants found to be ineligible after enrollment were excluded from the analysis

The number of participants that achieved a best overall response of CRi while on study. Complete Remission with Incomplete Blood Count Recovery (CRi): Same as for CR but without achievement of ANC at least 1000/uL (CRi) and/or platelet count of 100,000/uL (CRp).

Outcome measures

Outcome measures
Measure	Alisertib / MLN8237 n=39 Participants Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Number of Participants That Achieved Complete Remission With Incomplete Blood Count Recovery (CRi)	5 Participants

SECONDARY outcome

Timeframe: 1 Year

Population: The three participants found to be ineligible after enrollment were excluded from the analysis

The percentage of participants alive at one year

Outcome measures

Outcome measures
Measure	Alisertib / MLN8237 n=39 Participants Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
1 Year Overall Survival Rate	50 percentage of participants Interval 34.0 to 66.0

SECONDARY outcome

Timeframe: From the time of treatment response until death or disease progression (up to about one year)

Population: Participants that achieved a complete response

The median amount of time from achieving a complete remission to the first of disease recurrence or death. RFS applies only to the subset of patients who achieve a CR+CRi at the end of induction therapy. * Complete remission (CR): Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, existing extramedullary disease. If possible, at least one bone marrow biopsy should be performed to confirm CR. * Complete remission with incomplete blood count recovery (CRi): Same as CR but without achievement of specified ANC and/or platelet count * Recurrence/ morphologic relapse: reappearance of leukemic blasts in the peripheral blood or \>5% blasts in the bone marrow not attributable to any other cause

Outcome measures

Outcome measures
Measure	Alisertib / MLN8237 n=20 Participants Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Median Relapse Free Survival	NA Months Interval 7.1 to The median value and the upper limit of the confidence interval are not defined due to an insufficient number of patients experiencing relapse

SECONDARY outcome

Timeframe: From the time of first remission to disease progression or death, median duration of 12.8 months

Population: Participants that achieved a complete response

The median amount of time from first achieving remission to disease progression (with patients censored at death). * Complete remission (CR): Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, existing extramedullary disease. If possible, at least one bone marrow biopsy should be performed to confirm CR. * Complete remission with incomplete blood count recovery (CRi): Same as CR but without achievement of specified ANC and/or platelet count * Recurrence/ morphologic relapse: reappearance of leukemic blasts in the peripheral blood or \>5% blasts in the bone marrow not attributable to any other cause

Outcome measures

Outcome measures
Measure	Alisertib / MLN8237 n=20 Participants Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Median Duration of Remission	12.8 Months Interval 11.5 to 14.7

SECONDARY outcome

Timeframe: From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months

Population: The three participants found to be ineligible after enrollment were excluded from the analysis

Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4). Adverse events were considered to be Serious Adverse Events (SAE) if they were grade 3 or greater and deemed to be possibly, probably, or definitely related to the study treatment.

Outcome measures

Outcome measures
Measure	Alisertib / MLN8237 n=39 Participants Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Number of Participants With Serious Adverse Events	27 Participants

Adverse Events

Alisertib / MLN8237

Serious events: 27 serious events

Other events: 39 other events

Deaths: 20 deaths

Serious adverse events

Serious adverse events
Measure	Alisertib / MLN8237 n=39 participants at risk Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Investigations Alanine aminotransferase increased	7.7% 3/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Blood and lymphatic system disorders Anemia	28.2% 11/39 • Number of events 11 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Anorexia	23.1% 9/39 • Number of events 9 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Aspartate aminotransferase increased	5.1% 2/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Blood bilirubin increased	7.7% 3/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Colitis	2.6% 1/39 • Number of events 1 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Diarrhea	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Dysphagia	2.6% 1/39 • Number of events 1 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Esophagitis	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Blood and lymphatic system disorders Febrile neutropenia	41.0% 16/39 • Number of events 19 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Hypophosphatemia	2.6% 1/39 • Number of events 1 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal mucositis	2.6% 1/39 • Number of events 1 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Mucositis oral	10.3% 4/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Nausea	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Neutrophil count decreased	30.8% 12/39 • Number of events 14 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Platelet count decreased	30.8% 12/39 • Number of events 17 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.

Other adverse events

Other adverse events
Measure	Alisertib / MLN8237 n=39 participants at risk Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Gastrointestinal disorders Abdominal distension	10.3% 4/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Abdominal pain	20.5% 8/39 • Number of events 10 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Renal and urinary disorders Acute kidney injury	12.8% 5/39 • Number of events 8 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Alanine aminotransferase increased	30.8% 12/39 • Number of events 14 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Alkaline phosphatase increased	38.5% 15/39 • Number of events 20 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Anal fistula	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Blood and lymphatic system disorders Anemia	33.3% 13/39 • Number of events 25 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Anorexia	59.0% 23/39 • Number of events 28 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Psychiatric disorders Anxiety	12.8% 5/39 • Number of events 5 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Aspartate aminotransferase increased	25.6% 10/39 • Number of events 13 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Cardiac disorders Atrial fibrillation	10.3% 4/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Blood bilirubin increased	33.3% 13/39 • Number of events 18 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Eye disorders Blurred vision	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Cardiac disorders Cardiac arrest	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Infections and infestations Catheter related infection	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
General disorders Chills	17.9% 7/39 • Number of events 7 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Colitis	12.8% 5/39 • Number of events 5 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Psychiatric disorders Confusion	15.4% 6/39 • Number of events 6 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Constipation	17.9% 7/39 • Number of events 7 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	20.5% 8/39 • Number of events 8 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Creatinine increased	5.1% 2/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Dehydration	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Psychiatric disorders Delirium	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Psychiatric disorders Depression	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Diarrhea	74.4% 29/39 • Number of events 35 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Nervous system disorders Dizziness	15.4% 6/39 • Number of events 7 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Dry mouth	7.7% 3/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Nervous system disorders Dysgeusia	10.3% 4/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Dyspepsia	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	25.6% 10/39 • Number of events 11 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
General disorders Edema limbs	17.9% 7/39 • Number of events 7 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Enterocolitis	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	12.8% 5/39 • Number of events 5 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Esophagitis	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Injury, poisoning and procedural complications Fall	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
General disorders Fatigue	56.4% 22/39 • Number of events 24 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Blood and lymphatic system disorders Febrile neutropenia	38.5% 15/39 • Number of events 20 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
General disorders Fever	28.2% 11/39 • Number of events 14 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Eye disorders Floaters	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	10.3% 4/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other, Lack of Appetite	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Nervous system disorders Headache	20.5% 8/39 • Number of events 10 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Vascular disorders Hematoma	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Hyperglycemia	7.7% 3/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Hypernatremia	10.3% 4/39 • Number of events 5 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Vascular disorders Hypertension	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Hyperuricemia	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Hypokalemia	7.7% 3/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Hyponatremia	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Metabolism and nutrition disorders Hypophosphatemia	10.3% 4/39 • Number of events 6 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Vascular disorders Hypotension	15.4% 6/39 • Number of events 6 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	23.1% 9/39 • Number of events 10 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Psychiatric disorders Insomnia	23.1% 9/39 • Number of events 9 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
General disorders Localized edema	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Infections and infestations Lung infection	25.6% 10/39 • Number of events 10 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Mucositis oral	38.5% 15/39 • Number of events 17 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Nausea	53.8% 21/39 • Number of events 27 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Neutrophil count decreased	23.1% 9/39 • Number of events 15 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
General disorders Non-cardiac chest pain	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Oral pain	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
General disorders Pain	7.7% 3/39 • Number of events 6 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Cardiac disorders Pericardial effusion	10.3% 4/39 • Number of events 5 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Nervous system disorders Peripheral sensory neuropathy	5.1% 2/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations Platelet count decreased	28.2% 11/39 • Number of events 31 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	15.4% 6/39 • Number of events 6 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Skin and subcutaneous tissue disorders Pruritus	7.7% 3/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	12.8% 5/39 • Number of events 6 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	38.5% 15/39 • Number of events 18 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	7.7% 3/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Infections and infestations Sepsis	15.4% 6/39 • Number of events 7 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Cardiac disorders Sinus bradycardia	10.3% 4/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Nervous system disorders Sinus pain	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Cardiac disorders Sinus tachycardia	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Nervous system disorders Somnolence	5.1% 2/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Respiratory, thoracic and mediastinal disorders Sore throat	10.3% 4/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Nervous system disorders Syncope	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Vascular disorders Thromboembolic event	10.3% 4/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Renal and urinary disorders Urinary urgency	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Cardiac disorders Ventricular arrhythmia	5.1% 2/39 • Number of events 2 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Cardiac disorders Ventricular tachycardia	7.7% 3/39 • Number of events 3 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Gastrointestinal disorders Vomiting	17.9% 7/39 • Number of events 9 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.
Investigations White blood cell decreased	5.1% 2/39 • Number of events 4 • From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months The adverse events reported in the serious adverse event section represent CTCAE 4 grade 3 or greater adverse events that were deemed to be possibly, probably, or definitely related to study treatment.

Additional Information

Amir Fathi, MD

Massachusetts General Hospital

Phone: 617-724-1124

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place