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Trial record 9 of 50 for:    "Essential Thrombocythemia" | "Anti-Infective Agents"

CC-4047 in Treating Patients With Myelofibrosis

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: NCT00669578
Recruitment Status : Active, not recruiting
First Posted : April 30, 2008
Results First Posted : May 9, 2014
Last Update Posted : March 1, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Chronic Myeloproliferative Disorders
Secondary Myelofibrosis
Intervention Drug: CC-4047
Enrollment 77
Recruitment Details This study opened June 2008 and accrued 12 Phase I participants and 65 Phase II participants before being closed in January 2010.
Pre-assignment Details Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts. Dose Limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. However, efficacy was not improved at higher doses and the most effective dose level was deemed 0.5 mg/day.
Arm/Group Title Phase I Phase II
Hide Arm/Group Description Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity. All patients enrolled to this phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Period Title: Overall Study
Started 12 65
Completed 12 65
Not Completed 0 0
Arm/Group Title Phase II Phase I Total
Hide Arm/Group Description All patients enrolled to this Phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle. Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity. Total of all reporting groups
Overall Number of Baseline Participants 65 12 77
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 65 participants 12 participants 77 participants
68
(42 to 87)
66
(51 to 83)
67
(42 to 87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 12 participants 77 participants
Female
18
  27.7%
7
  58.3%
25
  32.5%
Male
47
  72.3%
5
  41.7%
52
  67.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 65 participants 12 participants 77 participants
65 12 77
1.Primary Outcome
Title Determine the Maximum Tolerated Dose of CC-4047
Hide Description Starting at a dose level of 2.5 mg/d on days 1-21 in every 28 day cycle, participants were accrued in cohorts of three to assess dose limiting toxicities (DLT) and determine the maximum tolerated dose (MTD). Dose escalation at increments of 0.5 mg/d was done if no subject had a DLT (a grade 4 or higher hematologic toxicity or a grade 3 or higher febrile neutropenia or a grade 3 or higher non-hematologic toxicity) in cycle 1. Subsequent cohorts were treated until the maximum tolerated dose (MTD) was reached (dose level before that which results in a DLT in >1 of 6 subjects). Subsequent participants were treated at the MTD, those without response at the MTD after 3 cycles were lowered to the minimal efficacious dose (MED) of 0.5 mg daily. Here, we are reporting the percentage of participants in Phase I with a DLT at each dose level.
Time Frame The first 28-day cycle of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
None of the Phase II participants were evaluable for this endpoint. For the Phase I portion of this study, three participants were accrued at a 2.5 mg/day dose level, six at the 3.0 mg/day dose level, and three at the 3.5 mg/day dose level.
Arm/Group Title Phase I Phase II
Hide Arm/Group Description:
Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.
All patients enrolled to this phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Overall Number of Participants Analyzed 12 0
Measure Type: Number
Unit of Measure: percentage of participants with DLT
2.5 mg/day 0
3.0 mg/day 0
3.5 mg/day 66
2.Primary Outcome
Title Best Overall Response Over the First 6 Cycles of Treatment
Hide Description

Response evaluation:

Complete Remission (CR):

Neutrophil count between 1 to 10 x 10^9/L without peripheral blasts in blood or bone marrow.

Partial Hematologic Response/Partial Remission (PR):

Increase in neutrophil by 50% + above 10^9/L for neutropenia)

Clinical Improvement (CI):

Increase in Neutrophil count, hemoglobin, platelet count or reduction in blood/marrow blasts.

Time Frame Every cycle of treatment for 6 cycles. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
None of the participants from the Phase I cohort were analyzed for this endpoint. All 65 Phase II participants were evaluable for this endpoint and included in the analysis.
Arm/Group Title Phase II Phase I
Hide Arm/Group Description:
All patients enrolled to this Phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.
Overall Number of Participants Analyzed 65 0
Measure Type: Number
Unit of Measure: participants
Complete Remission 0
Partial Remission 0
Clinical Improvement 9
3.Secondary Outcome
Title Number of Participants With Treatment Related Adverse Events.
Hide Description Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. The number of participants with grade 3 or higher adverse events at least possibly related to study treatment are reported here.
Time Frame During treatment and every 6 months until 3 years from registration or progression.
Hide Outcome Measure Data
Hide Analysis Population Description
None of the Phase I participants were used for this primary endpoint. All 65 Phase II participants were evaluable for this endpoint.
Arm/Group Title Phase II Phase I
Hide Arm/Group Description:
All patients enrolled to this Phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.
Overall Number of Participants Analyzed 65 0
Measure Type: Number
Unit of Measure: participants
Grade 3 or Higher 6
Grade 4 or Higher 3
Grade 5 0
4.Secondary Outcome
Title Duration of Response Time
Hide Description Duration of response is defined as the date at which the patient’s objective status is first noted to be a CR, PR or CI to the date progression is documented (if one has occurred) or to the date of last follow-up(for those patients who have not progressed).
Time Frame Time from response to disease progression, intolerance of study drug, or death.
Hide Outcome Measure Data
Hide Analysis Population Description
None of the Phase I participants were evaluable for this endpoint. Sixty-five (65) participants were recruited for the Phase II portion. Results presented here are on the 9 Phase II patients who responded to treatment.
Arm/Group Title Phase II Phase I
Hide Arm/Group Description:
All patients enrolled to this Phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.
Overall Number of Participants Analyzed 9 0
Median (95% Confidence Interval)
Unit of Measure: Months
5.6
(1.9 to 13.8)
5.Secondary Outcome
Title Time to Response
Hide Description The time to response is defined as the time from study registration to the first date at which the patient’s objective status was classified as a response (CR, PR or CI). In patients who do not achieve a response, time to response will be censored at the patient’s last evaluation date. The distribution for each of these event-time variables (duration of response and time to response) will be estimated by Kaplan-Meier curves.
Time Frame Time from registration to the first date of response within twelve 28-day cycles of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
None of the Phase I participants were evaluable for this endpoint. Sixty-five (65) patients were recruited for the Phase II portion. Only 9 of the 65 patients achieved a response. Thus, the median of time to response and the upper limit of 95% confidence interval are not attainable.
Arm/Group Title Phase II Phase I
Hide Arm/Group Description:
All patients enrolled to this Phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Every 28 day cycle while on treatment (up to 12 cycles).
Adverse Event Reporting Description The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
 
Arm/Group Title Phase II
Hide Arm/Group Description All patients enrolled to this Phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
All-Cause Mortality
Phase II
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Phase II
Affected / at Risk (%) # Events
Total   19/65 (29.23%)    
Blood and lymphatic system disorders   
Hemoglobin decreased  1  2/65 (3.08%)  2
Cardiac disorders   
Myocardial ischemia  1  1/65 (1.54%)  1
Gastrointestinal disorders   
Diarrhea  1  1/65 (1.54%)  1
Esophageal varices hemorrhage  1  1/65 (1.54%)  1
Gastrointestinal disorder  1  1/65 (1.54%)  1
Lower gastrointestinal hemorrhage  1  1/65 (1.54%)  1
Upper gastrointestinal hemorrhage  1  1/65 (1.54%)  1
General disorders   
Edema limbs  1  1/65 (1.54%)  1
Fatigue  1  1/65 (1.54%)  1
Multi-organ failure  1  1/65 (1.54%)  1
Immune system disorders   
Hypersensitivity  1  1/65 (1.54%)  1
Infections and infestations   
Infectious meningitis  1  1/65 (1.54%)  1
Pneumonia  1  4/65 (6.15%)  4
Upper respiratory infection  1  1/65 (1.54%)  1
Investigations   
Leukocyte count decreased  1  2/65 (3.08%)  2
Neutrophil count decreased  1  1/65 (1.54%)  1
Platelet count decreased  1  1/65 (1.54%)  1
Metabolism and nutrition disorders   
Tumor lysis syndrome  1  1/65 (1.54%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  1/65 (1.54%)  1
Hypoxia  1  1/65 (1.54%)  1
Laryngeal edema  1  1/65 (1.54%)  1
Skin and subcutaneous tissue disorders   
Skin ulceration  1  1/65 (1.54%)  1
Vascular disorders   
Hematoma  1  1/65 (1.54%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase II
Affected / at Risk (%) # Events
Total   65/65 (100.00%)    
Blood and lymphatic system disorders   
Hemoglobin decreased  1  53/65 (81.54%)  214
Cardiac disorders   
Left ventricular dysfunction  1  1/65 (1.54%)  1
Endocrine disorders   
Hypothyroidism  1  1/65 (1.54%)  1
Gastrointestinal disorders   
Constipation  1  1/65 (1.54%)  1
Diarrhea  1  10/65 (15.38%)  19
Nausea  1  9/65 (13.85%)  16
Vomiting  1  3/65 (4.62%)  4
General disorders   
Edema limbs  1  1/65 (1.54%)  1
Fatigue  1  65/65 (100.00%)  477
Localized edema  1  1/65 (1.54%)  1
Pain  1  2/65 (3.08%)  2
Immune system disorders   
Hypersensitivity  1  1/65 (1.54%)  1
Infections and infestations   
Skin infection  1  1/65 (1.54%)  1
Investigations   
Alkaline phosphatase increased  1  1/65 (1.54%)  1
Leukocyte count decreased  1  15/65 (23.08%)  54
Neutrophil count decreased  1  27/65 (41.54%)  196
Platelet count decreased  1  43/65 (66.15%)  274
Metabolism and nutrition disorders   
Blood uric acid increased  1  7/65 (10.77%)  11
Serum potassium increased  1  2/65 (3.08%)  3
Serum sodium decreased  1  1/65 (1.54%)  1
Musculoskeletal and connective tissue disorders   
Joint effusion  1  1/65 (1.54%)  1
Pain in extremity  1  1/65 (1.54%)  1
Nervous system disorders   
Peripheral sensory neuropathy  1  18/65 (27.69%)  81
Renal and urinary disorders   
Hemorrhage urinary tract  1  1/65 (1.54%)  1
Protein urine positive  1  1/65 (1.54%)  1
Renal failure  1  2/65 (3.08%)  2
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  1/65 (1.54%)  1
Skin and subcutaneous tissue disorders   
Pruritus  1  20/65 (30.77%)  36
Skin ulceration  1  1/65 (1.54%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10
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: Ayalew Tefferi, M.D.
Organization: Mayo Clinic
EMail: tefferi.ayalew@mayo.edu
Layout table for additonal information
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00669578     History of Changes
Other Study ID Numbers: MC078B
P30CA015083 ( U.S. NIH Grant/Contract )
MC078B ( Other Identifier: Mayo Clinic Cancer Center )
NCI-2009-01331 ( Registry Identifier: NCI-CTRP )
07-005317 ( Other Identifier: Mayo Clinic IRB )
PO-MMM-PI-0007 ( Other Identifier: Celgene Protocol )
First Submitted: April 29, 2008
First Posted: April 30, 2008
Results First Submitted: November 7, 2012
Results First Posted: May 9, 2014
Last Update Posted: March 1, 2019