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Trial record 1 of 1 for:    FCR Duvelisib CLL | United States
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A Phase 1b/2 Study of IPI-145 Plus FCR in Previously Untreated, Younger Patients With CLL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02158091
Recruitment Status : Active, not recruiting
First Posted : June 6, 2014
Results First Posted : December 11, 2018
Last Update Posted : December 30, 2019
Sponsor:
Collaborator:
Verastem, Inc.
Information provided by (Responsible Party):
Matthew S. Davids, MD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Lymphocytic Leukemia
Interventions Drug: IPI-145
Drug: Fludarabine
Drug: Cyclophosphamide
Drug: Rituximab
Enrollment 32
Recruitment Details Participants in the Phase I portion of the study enrolled in outpatient clinic setting from 6/27/2014 to 1/13/2015 and to the Phase II study from 4/14/2015 to 8/15/2016
Pre-assignment Details  
Arm/Group Title Phase I Cohort 1: IPI-145 25mg Once Daily + FCR Phase I Cohort 2 (MTD): IPI-145 25mg Twice Daily + FCR Phase II Dose Expansion(RP2D)-IPI-145 25mg Twice Daily + FCR
Hide Arm/Group Description Phase I Cohort 1 patients received oral agent IPI-145 25mg daily on days 1-28 of a 28 day cycle, except for Cycle 1, which lasts 35 with a 7 day IPI-145 run in, then will continue daily dosing for 6 cycles and up to 2 years of maintenance. Fludarabine, cyclophosphamide, rituximab (FCR) swill be given standard dosing intravenously (IV) Days 1-3 during week 1 of a cycle for up to 6 cycles, with dose reductions permitted. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities. Phase I Cohort 2 patients received oral agent IPI-145 25mg twice daily ( BID)on days 1-28 of a 28 day cycle, except for Cycle 1, which lasts 35 with a 7 day IPI-145 run in, then will continue daily dosing for 6 cycles and up to 2 years of maintenance. Fludarabine, cyclophosphamide, rituximab (FCR) swill be given standard dosing intravenously (IV) Days 1-3 during week 1 of a cycle for up to 6 cycles, with dose reductions permitted. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities. Phase II (MTD)CLL participants received the regimen established in the Phase I study ( January 2015). Phase II Participants received oral IPI-145 25mg twice daily (BID) for up to 6 cycles of combination therapy and 2 years of maintenance ( monotherapy) and received standard dosing if Fludarabine, Cyclophosphamide, and Rituxan (FCR) on days 1-3 of each cycle for up to 6 cycles. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.
Period Title: Overall Study
Started 6 6 20
Completed 4 5 20
Not Completed 2 1 0
Reason Not Completed
DLT             2             1             0
Arm/Group Title Phase I Cohort 1: IPI-145 25mg Once Daily + FCR Phase I Cohort 2: IPI-145 25mg Once Daily Phase II Dose Expansion ( MTD): IPI 145 25mg BID Total
Hide Arm/Group Description Phase I Cohort 1 patients received oral agent IPI-145 25mg daily on days 1-28 of a 28 day cycle, except for Cycle 1, which lasts 35 with a 7 day IPI-145 run in, then will continue daily dosing for 6 cycles and up to 2 years of maintenance. Fludarabine, cyclophosphamide, rituximab (FCR) swill be given standard dosing intravenously (IV) Days 1-3 during week 1 of a cycle for up to 6 cycles, with dose reductions permitted. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities. Phase I Cohort 2 patients received oral agent IPI-145 25mg twice BID) daily on days 1-28 of a 28 day cycle, except for Cycle 1, which lasts 35 with a 7 day IPI-145 run in, then will continue daily dosing for 6 cycles and up to 2 years of maintenance. Fludarabine, cyclophosphamide, rituximab (FCR) swill be given standard dosing intravenously (IV) Days 1-3 during week 1 of a cycle for up to 6 cycles, with dose reductions permitted. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities. Phase II (MTD) CLL participants received the regimen established in the Phase I study ( January 2015). Phase II Participants received oral IPI-145 25mg twice daily (BID) for up to 6 cycles of combination therapy and 2 years of maintenance ( monotherapy) and received standard dosing if Fludarabine, Cyclophosphamide, and Rituxan (FCR) on days 1-3 of each cycle for up to 6 cycles. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities. Total of all reporting groups
Overall Number of Baseline Participants 6 6 20 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 20 participants 32 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
 100.0%
5
  83.3%
20
 100.0%
31
  96.9%
>=65 years
0
   0.0%
1
  16.7%
0
   0.0%
1
   3.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 20 participants 32 participants
Female
1
  16.7%
3
  50.0%
6
  30.0%
10
  31.3%
Male
5
  83.3%
3
  50.0%
14
  70.0%
22
  68.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 20 participants 32 participants
Hispanic or Latino
0
   0.0%
1
  16.7%
1
   5.0%
2
   6.3%
Not Hispanic or Latino
6
 100.0%
5
  83.3%
17
  85.0%
28
  87.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
2
  10.0%
2
   6.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 20 participants 32 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
6
 100.0%
6
 100.0%
18
  90.0%
30
  93.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
2
  10.0%
2
   6.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 6 participants 20 participants 32 participants
6 6 20 32
1.Primary Outcome
Title Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I
Hide Description To assess the safety of IPI145 in combination with FCR in previously untreated younger patients with CLL. DLT is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. DLT refers to toxicities experienced at any time during the study treatment, defined as Grade 3 or greater hematologic toxicity (except Grade 3 or Grade 4 neutropenia or thrombocytopenia that lasts less than or equal to 10 days off treatment), any Grade 3 or greater non-hematologic toxicity (except Grade 3 or greater nausea, vomiting, diarrhea, Grade 3 infusion reactions), Grade 3 asymptomatic laboratory abnormalities that improve to grade 2 or less within 3 days, Inability to receive day 1 therapy of Cycle 2 even after a three week treatment delay due to drug related toxicity from prior cycle, and any Grade 4 or greater elevation in AST ALT values
Time Frame . Participants were assessed every week or more often as needed during Cycle 1, and every Day 1 Cycles 2 and onward-Dose-limiting toxicities (DLTs) occurring during the first cycle of treatment will be used in determining the Phase II MTD/RP2D
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who have received no prior therapy for CLL but who meet IW-CLL 2008 Criteria for requiring treatment
Arm/Group Title Phase I Cohort 1: IPI-145 25mg Once Daily + FCR Phase I Cohort 2 (MTD): IPI-145 25mg Twice Daily + FCR
Hide Arm/Group Description:
Phase I Cohort 1 patients received oral agent IPI-145 25mg daily on days 1-28 of a 28 day cycle, except for Cycle 1, which lasts 35 with a 7 day IPI-145 run in, then will continue daily dosing for 6 cycles and up to 2 years of maintenance. Fludarabine, cyclophosphamide, rituximab (FCR) swill be given standard dosing intravenously (IV) Days 1-3 during week 1 of a cycle for up to 6 cycles, with dose reductions permitted. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.
Phase I Cohort 2 patients received oral agent IPI-145 25mg twice daily ( BID)on days 1-28 of a 28 day cycle, except for Cycle 1, which lasts 35 with a 7 day IPI-145 run in, then will continue daily dosing for 6 cycles and up to 2 years of maintenance. Fludarabine, cyclophosphamide, rituximab (FCR) swill be given standard dosing intravenously (IV) Days 1-3 during week 1 of a cycle for up to 6 cycles, with dose reductions permitted. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.
Overall Number of Participants Analyzed 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
2
  33.3%
1
  16.7%
2.Primary Outcome
Title Number of Patients Who Had a Minimal Residual Disease (MRD) Negative Complete Response (CR) 2 Months After Chemotherapy
Hide Description To determine the rate of minimal residual disease negative complete response (MRD negative CR) in the bone marrow at 2 months post last cycle of FCR, participants will have a bone marrow biopsy procedure 2 months after completing combination therapy (IPI-145+ FCR) in tandem with a chest,neck, abdomen and pelvic PET CT scan. A central read of the PET CT scan will confirm a radiographic complete response, and the bone marrow pathology and morphology assessments will confirm morphological CR in the bone marrow, while MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4. This will include all patients treated and evaluable at maximum tolerated dose, and at the recommended phase II dose ( RP2D)
Time Frame 2 months after completion of combination therapy of IPI-145 and FCR
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I MTD and Phase II RP2D: IPI 145 25 mg BID + FCR
Hide Arm/Group Description:
Phase I Cohort 2 (MTD) patients and Dose Expansion patients (RP2D) received oral agent IPI-145 25mg twice daily (BID)on days 1-28 of a 28 day cycle, except for Cycle 1, which lasts 35 with a 7 day IPI-145 run in, then will continue daily dosing for 6 cycles and up to 2 years of maintenance. Fludarabine, cyclophosphamide, rituximab (FCR) swill be given standard dosing intravenously (IV) Days 1-3 during week 1 of a cycle for up to 6 cycles, with dose reductions permitted. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.
Overall Number of Participants Analyzed 26
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
23
(9 to 44)
3.Secondary Outcome
Title Overall Response Rate
Hide Description Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
Time Frame At baseline, End of Cycle 3, and 2 months post FCR
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Number of Participants With Serious and Non-Serious Adverse Events
Hide Description Toxicity assessments will be done using the CTEP Version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) and will include all participants who have received at least 1 dose of IPI-145. Toxicities will be assessed at minimum every week during cycle 1, on Day 1 of every cycle during Cycle 2 onward, and every other cycle Day 1 during maintenance.
Time Frame Up to 210 days
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Rate of Minimal Residual Disease (MRD) in the Peripheral Blood
Hide Description Participants will have MRD testing in the peripheral blood by four-color flow cytometry at the end of cycle 3, 2 months post combination therapy, and every 6 months thereafter for the duration of treatment and subsequent follow up
Time Frame 2 Years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Rate of Treatment Related Adverse Effects
Hide Description Participants will be evaluable for this endpoint if they have had at least 1 dose of study treatment. Toxicities will be assessed at minimum each week during cycle 1, and each day 1 during combination therapy, and then every two months thereafter. CTCAE version 4.0 will be used to assess toxicity term and grading.
Time Frame 210 days
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Determine the Association of Established CLL Prognostic Factors With Clinical Response
Hide Description Fisher's exact test for categorical variables and Wilcoxon's rank sum test will be used-
Time Frame 2 Years
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Rate of Complete Response and Partial Response
Hide Description Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
Time Frame At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Rate of Progression Free Survival
Hide Description 2008 IW-CLL criteria
Time Frame At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Event Free Survival Rate
Hide Description Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
Time Frame At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Duration of Remission Rate
Hide Description Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)Frequency of follow up visits and scans are per MD discretion. Recommended follow up visits for a minimum of one year
Time Frame At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter
Outcome Measure Data Not Reported
Time Frame Adverse events are assessed at minimum every week during cycle 1, and day 1 of every cycle thereafter during combination, and every two cycles thereafter while in maintenance. Treatment duration in cycles was a a median of 6 cycles in Phase I Cohort 1, 4.5 cycles in Phase I Cohort 2 and 5.5 cycles in the Phase II MTD
Adverse Event Reporting Description Maximum grade toxicity by type-Serious AEs were defined as per DFCI criteria: Any grade 2 or 3 unexpected and treatment related event, and all grade 4 and 5 events regardless of attribution to study treatment, and includes events deemed medically important by overall PI. Other AEs were defined as events with the attribution of at least possibly related to the study treatment that did not meet the SAE criteria. CTCAE 4.0 was used in investigator assessment and lab value review.
 
Arm/Group Title Phase 1 Cohort 1: IPI-145 25mg Once Daily + FCR Phase 1 Cohort 2: IPI-145 25mg Twice Daily + FCR Phase II Dose Expansion(MTD)-IPI-145 25mg Twice Daily + FCR
Hide Arm/Group Description Phase I Cohort 1 patients received oral agent IPI-145 25mg daily on days 1-28 of a 28 day cycle, except for Cycle 1, which lasts 35 with a 7 day IPI-145 run in, then will continue daily dosing for 6 cycles and up to 2 years of maintenance. Fludarabine, cyclophosphamide, rituximab (FCR) swill be given standard dosing intravenously (IV) Days 1-3 during week 1 of a cycle for up to 6 cycles, with dose reductions permitted. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities. Phase I Cohort 2 patients received oral agent IPI-145 25mg twice daily ( BID)on days 1-28 of a 28 day cycle, except for Cycle 1, which lasts 35 with a 7 day IPI-145 run in, then will continue daily dosing for 6 cycles and up to 2 years of maintenance. Fludarabine, cyclophosphamide, rituximab (FCR) swill be given standard dosing intravenously (IV) Days 1-3 during week 1 of a cycle for up to 6 cycles, with dose reductions permitted. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities. Phase II (MTD)CLL participants received the regimen established in the Phase I study ( January 2015). Phase II Participants received oral IPI-145 25mg twice daily (BID) for up to 6 cycles of combination therapy and 2 years of maintenance ( monotherapy) and received standard dosing if Fludarabine, Cyclophosphamide, and Rituxan (FCR) on days 1-3 of each cycle for up to 6 cycles. Patients are treated until progression without clinical benefit, toxicity, or withdrawal of consent by the patient, or closure of the trial by the Overall PI or regulatory authorities.
All-Cause Mortality
Phase 1 Cohort 1: IPI-145 25mg Once Daily + FCR Phase 1 Cohort 2: IPI-145 25mg Twice Daily + FCR Phase II Dose Expansion(MTD)-IPI-145 25mg Twice Daily + FCR
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)      0/6 (0.00%)      0/20 (0.00%)    
Hide Serious Adverse Events
Phase 1 Cohort 1: IPI-145 25mg Once Daily + FCR Phase 1 Cohort 2: IPI-145 25mg Twice Daily + FCR Phase II Dose Expansion(MTD)-IPI-145 25mg Twice Daily + FCR
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      6/6 (100.00%)      20/20 (100.00%)    
Blood and lymphatic system disorders       
Febrile neutropenia  1  2/6 (33.33%)  2 1/6 (16.67%)  1 2/20 (10.00%)  2
Cardiac disorders       
Pericarditis  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/20 (5.00%)  1
Gastrointestinal disorders       
Colitis  1  0/6 (0.00%)  0 0/6 (0.00%)  0 4/20 (20.00%)  4
Hepatobiliary disorders       
Drug Induced Liver Injury  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/20 (5.00%)  1
Pancreatitis  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/20 (5.00%)  1
Blood Bilirubin Increased  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/20 (5.00%)  1
Immune system disorders       
Inflammatory Bursitis  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/20 (5.00%)  1
Pityriasis Rubra Pilaris Reaction  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/20 (5.00%)  1
Infections and infestations       
Sinusitis  1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/20 (0.00%)  0
Investigations       
Thrombocytopenia  1  1/6 (16.67%)  1 3/6 (50.00%)  3 5/20 (25.00%)  5
Leukopenia  1  3/6 (50.00%)  3 3/6 (50.00%)  3 4/20 (20.00%)  4
Neutrophil Count Decrease  1  5/6 (83.33%)  5 4/6 (66.67%)  4 10/20 (50.00%)  10
Lymphopenia  1  5/6 (83.33%)  5 4/6 (66.67%)  4 5/20 (25.00%)  5
Lipase Increased  1  0/6 (0.00%)  0 1/6 (16.67%)  1 1/20 (5.00%)  1
Alanine Aminotransferase Increased  1  0/6 (0.00%)  0 1/6 (16.67%)  1 3/20 (15.00%)  3
Aspartate Aminotransferase Increased  1  0/6 (0.00%)  0 1/6 (16.67%)  1 3/20 (15.00%)  3
Alkaline Phosphatase Increased  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/20 (5.00%)  1
Amylase Increased  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/20 (5.00%)  1
Metabolism and nutrition disorders       
Dehydration  1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/20 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Neck Stiffness  1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/20 (5.00%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Myelodysplastic Syndrome  1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/20 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Lung Infection  1  2/6 (33.33%)  2 2/6 (33.33%)  2 1/20 (5.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1 Cohort 1: IPI-145 25mg Once Daily + FCR Phase 1 Cohort 2: IPI-145 25mg Twice Daily + FCR Phase II Dose Expansion(MTD)-IPI-145 25mg Twice Daily + FCR
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      6/6 (100.00%)      20/20 (100.00%)    
Blood and lymphatic system disorders       
Anemia  1  3/6 (50.00%)  2/6 (33.33%)  7/20 (35.00%) 
Edema limbs  1  1/6 (16.67%)  1/6 (16.67%)  2/20 (10.00%) 
Febrile neutropenia  1  1/6 (16.67%)  1/6 (16.67%)  2/20 (10.00%) 
Leukocytosis  1  0/6 (0.00%)  0/6 (0.00%)  2/20 (10.00%) 
Cardiac disorders       
Cardiac disorders - Other, specify  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Ear and labyrinth disorders       
Tinnitus  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Eye disorders       
Blurred vision  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Eye disorders - Other, specify  1  0/6 (0.00%)  2/6 (33.33%)  1/20 (5.00%) 
Eye pain  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  1/6 (16.67%)  0/6 (0.00%)  3/20 (15.00%) 
Bloating  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Colitis  1  0/6 (0.00%)  0/6 (0.00%)  2/20 (10.00%) 
Constipation  1  5/6 (83.33%)  2/6 (33.33%)  2/20 (10.00%) 
Diarrhea  1  4/6 (66.67%)  2/6 (33.33%)  9/20 (45.00%) 
Dry mouth  1  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
Dyspepsia  1  0/6 (0.00%)  0/6 (0.00%)  2/20 (10.00%) 
Esophageal pain  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Gastroesophageal reflux disease  1  0/6 (0.00%)  1/6 (16.67%)  2/20 (10.00%) 
Gastrointestinal disorders - Other, specify  1  4/6 (66.67%)  2/6 (33.33%)  4/20 (20.00%) 
Mucositis oral  1  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Nausea  1  6/6 (100.00%)  5/6 (83.33%)  12/20 (60.00%) 
Oral pain  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Stomach pain  1  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
Tooth discoloration  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Vomiting  1  4/6 (66.67%)  1/6 (16.67%)  4/20 (20.00%) 
General disorders       
Fatigue  1  6/6 (100.00%)  6/6 (100.00%)  10/20 (50.00%) 
General disorders and administration site conditions - Other, specify  1  3/6 (50.00%)  0/6 (0.00%)  3/20 (15.00%) 
Malaise  1  1/6 (16.67%)  0/6 (0.00%)  2/20 (10.00%) 
Pain  1  1/6 (16.67%)  1/6 (16.67%)  2/20 (10.00%) 
Immune system disorders       
Fever  1  4/6 (66.67%)  4/6 (66.67%)  9/20 (45.00%) 
Flu like symptoms  1  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Infections and infestations       
Infections and infestations - Other, specify  1  2/6 (33.33%)  0/6 (0.00%)  1/20 (5.00%) 
Lung infection  1  0/6 (0.00%)  1/6 (16.67%)  1/20 (5.00%) 
Upper respiratory infection  1  3/6 (50.00%)  2/6 (33.33%)  2/20 (10.00%) 
Urinary tract infection  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Vaginal infection  1  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Wound infection  1  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Injury, poisoning and procedural complications       
Bruising  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Injury, poisoning and procedural complications - Other, specify  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Investigations       
Alanine aminotransferase increased  1  2/6 (33.33%)  1/6 (16.67%)  8/20 (40.00%) 
Alkaline phosphatase increased  1  0/6 (0.00%)  1/6 (16.67%)  3/20 (15.00%) 
Aspartate aminotransferase increased  1  2/6 (33.33%)  1/6 (16.67%)  7/20 (35.00%) 
Blood bilirubin increased  1  0/6 (0.00%)  0/6 (0.00%)  2/20 (10.00%) 
Investigations - Other, specify  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Lipase increased  1  0/6 (0.00%)  1/6 (16.67%)  1/20 (5.00%) 
Lymphocyte count decreased  1  3/6 (50.00%)  2/6 (33.33%)  4/20 (20.00%) 
Lymphocyte count increased  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Neutrophil count decreased  1  5/6 (83.33%)  3/6 (50.00%)  9/20 (45.00%) 
Platelet count decreased  1  6/6 (100.00%)  2/6 (33.33%)  10/20 (50.00%) 
Serum amylase increased  1  0/6 (0.00%)  1/6 (16.67%)  1/20 (5.00%) 
Weight gain  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Weight loss  1  2/6 (33.33%)  1/6 (16.67%)  0/20 (0.00%) 
White blood cell decreased  1  6/6 (100.00%)  4/6 (66.67%)  4/20 (20.00%) 
Metabolism and nutrition disorders       
Anorexia  1  5/6 (83.33%)  3/6 (50.00%)  3/20 (15.00%) 
Dehydration  1  2/6 (33.33%)  1/6 (16.67%)  0/20 (0.00%) 
Hyperglycemia  1  2/6 (33.33%)  0/6 (0.00%)  0/20 (0.00%) 
Hyperuricemia  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Hypoalbuminemia  1  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Hypoglycemia  1  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
Hypophosphatemia  1  1/6 (16.67%)  1/6 (16.67%)  1/20 (5.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/6 (0.00%)  0/6 (0.00%)  2/20 (10.00%) 
Back pain  1  2/6 (33.33%)  0/6 (0.00%)  1/20 (5.00%) 
Bone pain  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Flank pain  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Generalized muscle weakness  1  2/6 (33.33%)  1/6 (16.67%)  0/20 (0.00%) 
Muscle weakness lower limb  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Musculoskeletal and connective tissue disorder - Other, specify  1  2/6 (33.33%)  4/6 (66.67%)  2/20 (10.00%) 
Myalgia  1  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Non-cardiac chest pain  1  1/6 (16.67%)  0/6 (0.00%)  3/20 (15.00%) 
Pain in extremity  1  1/6 (16.67%)  2/6 (33.33%)  0/20 (0.00%) 
Nervous system disorders       
Dizziness  1  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
Dysgeusia  1  0/6 (0.00%)  1/6 (16.67%)  3/20 (15.00%) 
Headache  1  3/6 (50.00%)  1/6 (16.67%)  2/20 (10.00%) 
Nervous system disorders - Other, specify  1  0/6 (0.00%)  1/6 (16.67%)  1/20 (5.00%) 
Paresthesia  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Peripheral motor neuropathy  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Peripheral sensory neuropathy  1  0/6 (0.00%)  0/6 (0.00%)  3/20 (15.00%) 
Syncope  1  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
Tremor  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Psychiatric disorders       
Anxiety  1  2/6 (33.33%)  1/6 (16.67%)  0/20 (0.00%) 
Depression  1  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Insomnia  1  3/6 (50.00%)  1/6 (16.67%)  1/20 (5.00%) 
Restlessness  1  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
Renal and urinary disorders       
Renal and urinary disorders - Other, specify  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Allergic rhinitis  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Cough  1  4/6 (66.67%)  4/6 (66.67%)  4/20 (20.00%) 
Dyspnea  1  4/6 (66.67%)  1/6 (16.67%)  6/20 (30.00%) 
Hiccups  1  1/6 (16.67%)  0/6 (0.00%)  2/20 (10.00%) 
Laryngeal inflammation  1  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Nasal congestion  1  2/6 (33.33%)  0/6 (0.00%)  0/20 (0.00%) 
Pharyngeal necrosis  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Postnasal drip  1  1/6 (16.67%)  0/6 (0.00%)  2/20 (10.00%) 
Productive cough  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders  1  0/6 (0.00%)  0/6 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders - Other, specify  1  1/6 (16.67%)  1/6 (16.67%)  0/20 (0.00%) 
Sore throat  1  1/6 (16.67%)  0/6 (0.00%)  1/20 (5.00%) 
Wheezing  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  2/6 (33.33%)  1/6 (16.67%)  0/20 (0.00%) 
Dry skin  1  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
Hyperhidrosis  1  2/6 (33.33%)  1/6 (16.67%)  1/20 (5.00%) 
Pruritus  1  4/6 (66.67%)  0/6 (0.00%)  1/20 (5.00%) 
Rash acneiform  1  0/6 (0.00%)  1/6 (16.67%)  1/20 (5.00%) 
Rash maculo-papular  1  0/6 (0.00%)  0/6 (0.00%)  4/20 (20.00%) 
Skin and subcutaneous tissue disorders - Other, specify  1  4/6 (66.67%)  2/6 (33.33%)  0/20 (0.00%) 
Skin/subcutaneous tissue disorders; Other, specify  1  1/6 (16.67%)  4/6 (66.67%)  3/20 (15.00%) 
Vascular disorders       
Chills  1  4/6 (66.67%)  1/6 (16.67%)  2/20 (10.00%) 
Flushing  1  1/6 (16.67%)  0/6 (0.00%)  0/20 (0.00%) 
Hypotension  1  0/6 (0.00%)  1/6 (16.67%)  1/20 (5.00%) 
Vascular disorders - Other, specify  1  0/6 (0.00%)  1/6 (16.67%)  0/20 (0.00%) 
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
Layout table for Results Point of Contact information
Name/Title: Matthew Davids, MD
Organization: Dana-Farber Cancer Institute
Phone: 617-632-6331
EMail: matthew_davids@dfci.harvard.edu
Layout table for additonal information
Responsible Party: Matthew S. Davids, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02158091    
Other Study ID Numbers: 14-193
First Submitted: June 4, 2014
First Posted: June 6, 2014
Results First Submitted: October 30, 2018
Results First Posted: December 11, 2018
Last Update Posted: December 30, 2019