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

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ClinicalTrials.gov Identifier: NCT02560025
Recruitment Status : Active, not recruiting
First Posted : September 25, 2015
Results First Posted : October 11, 2018
Last Update Posted : March 8, 2019
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Amir Fathi, Massachusetts General Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Myeloid Leukemia
Interventions Drug: Alisertib
Drug: Cytarabine
Drug: Idarubicin
Drug: Daunorubicin
Enrollment 42
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Alisertib / MLN8237
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 42
Completed 39
Not Completed 3
Reason Not Completed
Ineligible after consent/ registration             3
Arm/Group Title Alisertib / MLN8237
Hide Arm/Group Description 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 Number of Baseline Participants 39
Hide Baseline Analysis Population Description
The three participants found to be ineligible after enrollment were excluded from the analysis
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 39 participants
67
(33 to 83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
Female
14
  35.9%
Male
25
  64.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
38
  97.4%
More than one race
0
   0.0%
Unknown or Not Reported
1
   2.6%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 39 participants
39
 100.0%
Cytogenetic Risk   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
High
13
  33.3%
Intermediate
26
  66.7%
[1]
Measure Description: Higher risk represents an increased chance that the participant will experience undesirable disease outcomes.
Median White Blood Cell (WBC) Count  
Median (Full Range)
Unit of measure:  Thousand WBC/ microliter blood
Number Analyzed 39 participants
3.2
(0.4 to 59.7)
1.Primary Outcome
Title Number of Participants That Achieved Complete Remission
Hide Description

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.

Time Frame From the start of treatment until the end of study treatment, up to approximately 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The three participants found to be ineligible after enrollment were excluded from the analysis
Arm/Group Title Alisertib / MLN8237
Hide Arm/Group Description:
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 Number of Participants Analyzed 39
Measure Type: Count of Participants
Unit of Measure: Participants
20
  51.3%
2.Primary Outcome
Title Number of Participants That Achieved Complete Remission With Incomplete Blood Count Recovery (CRi)
Hide Description

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).

Time Frame From the start of treatment until the end of study treatment, up to approximately 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The three participants found to be ineligible after enrollment were excluded from the analysis
Arm/Group Title Alisertib / MLN8237
Hide Arm/Group Description:
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 Number of Participants Analyzed 39
Measure Type: Count of Participants
Unit of Measure: Participants
5
  12.8%
3.Secondary Outcome
Title Overall Survival
Hide Description [Not Specified]
Time Frame 1 Year
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Relapse Free Survival
Hide Description [Not Specified]
Time Frame 1 Year
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Remission Duration
Hide Description [Not Specified]
Time Frame 2 Years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Number of Participants With Serious Adverse Events
Hide Description 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.
Time Frame From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
The three participants found to be ineligible after enrollment were excluded from the analysis
Arm/Group Title Alisertib / MLN8237
Hide Arm/Group Description:
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 Number of Participants Analyzed 39
Measure Type: Count of Participants
Unit of Measure: Participants
27
  69.2%
Time Frame From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months
Adverse Event Reporting Description 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.
 
Arm/Group Title Alisertib / MLN8237
Hide Arm/Group Description 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.
All-Cause Mortality
Alisertib / MLN8237
Affected / at Risk (%)
Total   5/39 (12.82%)    
Show Serious Adverse Events Hide Serious Adverse Events
Alisertib / MLN8237
Affected / at Risk (%) # Events
Total   27/39 (69.23%)    
Blood and lymphatic system disorders   
Anemia  1  11/39 (28.21%)  11
Febrile neutropenia  1  16/39 (41.03%)  19
Gastrointestinal disorders   
Colitis  1  1/39 (2.56%)  1
Diarrhea  1  2/39 (5.13%)  2
Dysphagia  1  1/39 (2.56%)  1
Esophagitis  1  2/39 (5.13%)  2
Mucositis oral  1  4/39 (10.26%)  4
Nausea  1  3/39 (7.69%)  3
Investigations   
Alanine aminotransferase increased  1  3/39 (7.69%)  4
Aspartate aminotransferase increased  1  2/39 (5.13%)  3
Blood bilirubin increased  1  3/39 (7.69%)  4
Neutrophil count decreased  1  12/39 (30.77%)  14
Platelet count decreased  1  12/39 (30.77%)  17
Metabolism and nutrition disorders   
Anorexia  1  9/39 (23.08%)  9
Hypophosphatemia  1  1/39 (2.56%)  1
Respiratory, thoracic and mediastinal disorders   
Laryngeal mucositis  1  1/39 (2.56%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alisertib / MLN8237
Affected / at Risk (%) # Events
Total   39/39 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  13/39 (33.33%)  25
Febrile neutropenia  1  15/39 (38.46%)  20
Cardiac disorders   
Atrial fibrillation  1  4/39 (10.26%)  4
Cardiac arrest  1  3/39 (7.69%)  3
Pericardial effusion  1  4/39 (10.26%)  5
Sinus bradycardia  1  4/39 (10.26%)  4
Sinus tachycardia  1  2/39 (5.13%)  2
Ventricular arrhythmia  1  2/39 (5.13%)  2
Ventricular tachycardia  1  3/39 (7.69%)  3
Eye disorders   
Blurred vision  1  2/39 (5.13%)  2
Floaters  1  2/39 (5.13%)  2
Gastrointestinal disorders   
Abdominal distension  1  4/39 (10.26%)  4
Abdominal pain  1  8/39 (20.51%)  10
Anal fistula  1  2/39 (5.13%)  2
Colitis  1  5/39 (12.82%)  5
Constipation  1  7/39 (17.95%)  7
Diarrhea  1  29/39 (74.36%)  35
Dry mouth  1  3/39 (7.69%)  4
Dyspepsia  1  3/39 (7.69%)  3
Enterocolitis  1  3/39 (7.69%)  3
Esophagitis  1  3/39 (7.69%)  3
Gastroesophageal reflux disease  1  4/39 (10.26%)  4
Gastrointestinal disorders - Other, Lack of Appetite  1  2/39 (5.13%)  2
Mucositis oral  1  15/39 (38.46%)  17
Nausea  1  21/39 (53.85%)  27
Oral pain  1  3/39 (7.69%)  3
Vomiting  1  7/39 (17.95%)  9
General disorders   
Chills  1  7/39 (17.95%)  7
Edema limbs  1  7/39 (17.95%)  7
Fatigue  1  22/39 (56.41%)  24
Fever  1  11/39 (28.21%)  14
Localized edema  1  2/39 (5.13%)  2
Non-cardiac chest pain  1  2/39 (5.13%)  2
Pain  1  3/39 (7.69%)  6
Infections and infestations   
Catheter related infection  1  2/39 (5.13%)  2
Lung infection  1  10/39 (25.64%)  10
Sepsis  1  6/39 (15.38%)  7
Injury, poisoning and procedural complications   
Fall  1  2/39 (5.13%)  2
Investigations   
Alanine aminotransferase increased  1  12/39 (30.77%)  14
Alkaline phosphatase increased  1  15/39 (38.46%)  20
Aspartate aminotransferase increased  1  10/39 (25.64%)  13
Blood bilirubin increased  1  13/39 (33.33%)  18
Creatinine increased  1  2/39 (5.13%)  3
Neutrophil count decreased  1  9/39 (23.08%)  15
Platelet count decreased  1  11/39 (28.21%)  31
White blood cell decreased  1  2/39 (5.13%)  4
Metabolism and nutrition disorders   
Anorexia  1  23/39 (58.97%)  28
Dehydration  1  2/39 (5.13%)  2
Hyperglycemia  1  3/39 (7.69%)  4
Hypernatremia  1  4/39 (10.26%)  5
Hyperuricemia  1  2/39 (5.13%)  2
Hypokalemia  1  3/39 (7.69%)  4
Hyponatremia  1  3/39 (7.69%)  3
Hypophosphatemia  1  4/39 (10.26%)  6
Musculoskeletal and connective tissue disorders   
Generalized muscle weakness  1  2/39 (5.13%)  2
Pain in extremity  1  2/39 (5.13%)  2
Nervous system disorders   
Dizziness  1  6/39 (15.38%)  7
Dysgeusia  1  4/39 (10.26%)  4
Headache  1  8/39 (20.51%)  10
Peripheral sensory neuropathy  1  2/39 (5.13%)  3
Sinus pain  1  2/39 (5.13%)  2
Somnolence  1  2/39 (5.13%)  3
Syncope  1  2/39 (5.13%)  2
Psychiatric disorders   
Anxiety  1  5/39 (12.82%)  5
Confusion  1  6/39 (15.38%)  6
Delirium  1  3/39 (7.69%)  3
Depression  1  2/39 (5.13%)  2
Insomnia  1  9/39 (23.08%)  9
Renal and urinary disorders   
Acute kidney injury  1  5/39 (12.82%)  8
Urinary urgency  1  2/39 (5.13%)  2
Respiratory, thoracic and mediastinal disorders   
Cough  1  8/39 (20.51%)  8
Dyspnea  1  10/39 (25.64%)  11
Epistaxis  1  5/39 (12.82%)  5
Hypoxia  1  9/39 (23.08%)  10
Pleural effusion  1  6/39 (15.38%)  6
Pulmonary edema  1  5/39 (12.82%)  6
Respiratory failure  1  3/39 (7.69%)  4
Sore throat  1  4/39 (10.26%)  4
Skin and subcutaneous tissue disorders   
Pruritus  1  3/39 (7.69%)  4
Rash maculo-papular  1  15/39 (38.46%)  18
Vascular disorders   
Hematoma  1  2/39 (5.13%)  2
Hypertension  1  3/39 (7.69%)  3
Hypotension  1  6/39 (15.38%)  6
Thromboembolic event  1  4/39 (10.26%)  4
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Amir Fathi, MD
Organization: Massachusetts General Hospital
Phone: 617-724-1124
Responsible Party: Amir Fathi, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02560025     History of Changes
Other Study ID Numbers: 15-334
First Submitted: September 23, 2015
First Posted: September 25, 2015
Results First Submitted: September 7, 2018
Results First Posted: October 11, 2018
Last Update Posted: March 8, 2019