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EL625 in Persistent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

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ClinicalTrials.gov Identifier: NCT00636155
Recruitment Status : Terminated (funding)
First Posted : March 14, 2008
Results First Posted : August 22, 2012
Last Update Posted : November 28, 2012
Sponsor:
Collaborator:
Eleos, Inc.
Information provided by (Responsible Party):
David Rizzieri, Duke University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Lymphoma, Small Lymphocytic
Leukemia, Lymphocytic, Chronic
Interventions Drug: cenersen sodium
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Fludarabine
Enrollment 20
Recruitment Details All patients were enrolled from Duke University Medical Center.
Pre-assignment Details  
Arm/Group Title All Patients
Hide Arm/Group Description EL625 2.4mg/kg/day as a continuous infusion daily for 4 days combined rituximab 375mg/m2 IV on day 2, fludarabine IV 25mg/m2 over 30 minutes on days 2- 4 and cyclophosphamide IV 250mg/m2 over 1 hour on days 2-4.
Period Title: Overall Study
Started 20
Completed 2 [1]
Not Completed 18
Reason Not Completed
Adverse Event             8
Lack of Efficacy             1
Withdrawal by Subject             3
Stem cell transplant             1
Physician Decision             5
[1]
Completed maximum 6 cycles of treatment
Arm/Group Title All Patients
Hide Arm/Group Description EL625 2.4mg/kg/day as a continuous infusion daily for 4 days combined rituximab 375mg/m2 IV on day 2, fludarabine IV 25mg/m2 over 30 minutes on days 2- 4 and cyclophosphamide IV 250mg/m2 over 1 hour on days 2-4.
Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
<=18 years
0
   0.0%
Between 18 and 65 years
12
  60.0%
>=65 years
8
  40.0%
Age Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 20 participants
62
(45 to 77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
3
  15.0%
Male
17
  85.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
American Indian or Alaska Native
1
   5.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   5.0%
White
18
  90.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Number of Patients With an Overall Response (Complete Response + Partial Response)
Hide Description Overall Response is the total number of participants with a Complete (CR) or Partial (PR) response. CR requires the absence of lymphadenopathy, hepatomegaly or splenomegaly and constitutional symptoms and a normal CBC; bone marrow must be at least normocellular for age, with less than 30% nucleated cells being lymphocytes with no lymphoid nodules. Partial Response: requires ≥ 50% decrease in one of the following: peripheral blood lymphocyte count, lymphadenopathy, enlargement of liver and/or spleen, or bone marrow involvement by CLL AND at least one hematologic parameter met for 2 months.
Time Frame every 3 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
Patients completing at least 2 cycles of treatment
Arm/Group Title All Patients
Hide Arm/Group Description:
Patients treated with cenersen, fludarabine, cyclphosphamide and rituximab
Overall Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: participants
9
2.Secondary Outcome
Title Progression Free Survival
Hide Description Progression is defined as at least one of the following: 1) ≥ 50% increase in the sum of the products of at least two lymph nodes one two consecutive determinations (at least one node must be ≥ 2 cm); appearance of new palpable lymph nodes, 2) ≥ 50% increase in the size of the liver and/or spleen; appearance of palpable hepatomegaly or splenomegaly, which was not previously present, 3) ≥ 50% increase in the absolute number of circulating lymphocytes to at least 5,000/µl or 4)Transformation to a more aggressive histology.
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received treatment
Arm/Group Title All Patients
Hide Arm/Group Description:
Patients treated with cenersen, fludarabine, cyclphosphamide and rituximab
Overall Number of Participants Analyzed 20
Median (95% Confidence Interval)
Unit of Measure: months
5.3
(4.7 to 14.0)
3.Secondary Outcome
Title Overall Survival
Hide Description [Not Specified]
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received treatment
Arm/Group Title All Patients
Hide Arm/Group Description:
Patients treated with cenersen, fludarabine, cyclphosphamide and rituximab
Overall Number of Participants Analyzed 20
Median (95% Confidence Interval)
Unit of Measure: months
10.6 [1] 
(5.37 to NA)
[1]
The upper limit of the confidence interval has not been reached/insufficient number of participants
Time Frame Adverse events were collected from the start of study treatment until 30 days after the last dose.
Adverse Event Reporting Description Other AE section contains all AEs, including SAEs, regardless of attribution to study drug
 
Arm/Group Title All Patients
Hide Arm/Group Description EL625 2.4mg/kg/day as a continuous infusion daily for 4 days combined rituximab 375mg/m2 IV on day 2, fludarabine IV 25mg/m2 over 30 minutes on days 2- 4 and cyclophosphamide IV 250mg/m2 over 1 hour on days 2-4.
All-Cause Mortality
All Patients
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
All Patients
Affected / at Risk (%) # Events
Total   8/20 (40.00%)    
Blood and lymphatic system disorders   
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe  1  3/20 (15.00%)  3
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)  1  1/20 (5.00%)  1
Investigations   
Neutrophils / granulocytes (ANC / AGC)  1  1/20 (5.00%)  1
Nervous system disorders   
Cognitive disturbance  1  1/20 (5.00%)  1
Syncope (fainting)  1  1/20 (5.00%)  1
Renal and urinary disorders   
Cystitis  1  1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders   
Hypoxia  1  1/20 (5.00%)  1
Skin and subcutaneous tissue disorders   
Ulceration  1  1/20 (5.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
All Patients
Affected / at Risk (%) # Events
Total   20/20 (100.00%)    
Blood and lymphatic system disorders   
Hemoglobin  1  10/20 (50.00%)  16
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)  1  1/20 (5.00%)  2
Febrile neutropenia (fever of unknown origin w/oclinically or microbiologically documented infe  1  7/20 (35.00%)  9
Pain - Lymph node  1  1/20 (5.00%)  1
Cardiac disorders   
Palpitations  1  2/20 (10.00%)  2
Supraventricular and nodal arrhythmia - Atrial fibrillation  1  1/20 (5.00%)  3
Supraventricular and nodal arrhythmia - Sinus bradycardia  1  2/20 (10.00%)  2
Supraventricular and nodal arrhythmia - Sinus tachycardia  1  1/20 (5.00%)  1
Cardiac General - Other  1  1/20 (5.00%)  1
Supraventricular and nodal arrhythmia - Atrial flutter  1  1/20 (5.00%)  1
Eye disorders   
Dry Eye Syndrome  1  1/20 (5.00%)  1
Vision - blurred vision  1  3/20 (15.00%)  3
Gastrointestinal disorders   
Constipation  1  7/20 (35.00%)  9
Diarrhea  1  5/20 (25.00%)  5
Dysphagia (difficulty swallowing  1  1/20 (5.00%)  1
Hemorrhoids  1  1/20 (5.00%)  1
Mucositis / stomatitis (clinical exam) - Oral cavity  1  3/20 (15.00%)  3
Nausea  1  8/20 (40.00%)  10
Obstruction, GI - Ileum  1  1/20 (5.00%)  1
Vomiting  1  1/20 (5.00%)  1
Pain - Abdomen NOS  1  1/20 (5.00%)  1
Pain - Dental / teeth / peridontal  1  1/20 (5.00%)  1
General disorders   
Fatigue (asthenia, lethargy, malaise)  1  11/20 (55.00%)  15
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10^9/L)  1  3/20 (15.00%)  3
Rigors / chills  1  5/20 (25.00%)  6
Edema: limb  1  4/20 (20.00%)  5
Pain - Other  1  1/20 (5.00%)  1
Hepatobiliary disorders   
Liver dysfunction / failure (clinical)  1  1/20 (5.00%)  1
Immune system disorders   
Allergic reaction / hypersensitivity (including drug fever)  1  2/20 (10.00%)  3
Allergy / Immunology - Other  1  2/20 (10.00%)  2
Infections and infestations   
Infection - Other  1  3/20 (15.00%)  4
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Bladder (urin  1  1/20 (5.00%)  1
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils-Lip / perioral  1  1/20 (5.00%)  2
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Rectum  1  2/20 (10.00%)  2
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Urinary tract  1  1/20 (5.00%)  1
Investigations   
Leukocytes (total WBC)  1  8/20 (40.00%)  13
Neutrophils / granulocytes (ANC / AGC)  1  6/20 (30.00%)  7
Platelets  1  14/20 (70.00%)  16
INR (International Normalized Ratio of prothrombin time  1  1/20 (5.00%)  1
Weight gain  1  2/20 (10.00%)  2
Weight loss  1  3/20 (15.00%)  3
Alkaline phosphatase  1  1/20 (5.00%)  1
AST, SGOT (serum glutamic oxaloacetic transaminase)  1  2/20 (10.00%)  2
Bilirubin (hyperbilirubinemia)  1  2/20 (10.00%)  2
Creatinine  1  2/20 (10.00%)  2
Metabolic / Laboratory - Other  1  2/20 (10.00%)  2
Metabolism and nutrition disorders   
Anorexia  1  5/20 (25.00%)  5
Albumin, serum-low (hypoalbuminemia)  1  3/20 (15.00%)  4
Calcium, serum-high (hypercalcemia)  1  1/20 (5.00%)  1
Calcium, serum-low (hypocalcemia)  1  4/20 (20.00%)  6
Glucose, serum-high (hyperglycemia)  1  5/20 (25.00%)  10
Magnesium, serum-low (hypomagnesemia)  1  3/20 (15.00%)  3
Potassium, serum-low (hypokalemia)  1  4/20 (20.00%)  4
Sodium, serum-low (hyponatremia)  1  3/20 (15.00%)  4
Uric Acid, serum-high (hyperuricemia)  1  1/20 (5.00%)  2
Musculoskeletal and connective tissue disorders   
Arthritis (non-septic)  1  2/20 (10.00%)  2
Joint-function  1  1/20 (5.00%)  1
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body / generalized  1  2/20 (10.00%)  2
Musculoskeletal - Flank pain  1  1/20 (5.00%)  1
Pain - Back  1  1/20 (5.00%)  1
Pain - Bone  1  1/20 (5.00%)  1
Pain - Chest wall  1  1/20 (5.00%)  1
Pain - Extremity-limb  1  1/20 (5.00%)  1
Pain - Joint  1  1/20 (5.00%)  1
Pain - Neck  1  1/20 (5.00%)  3
Nervous system disorders   
Taste Alteration (dysgeusia)  1  2/20 (10.00%)  3
Cognitive disturbance  1  1/20 (5.00%)  1
Dizziness  1  4/20 (20.00%)  7
Memory Impairment  1  2/20 (10.00%)  2
Neuropathy: motor  1  1/20 (5.00%)  1
Neuropathy: sensory  1  2/20 (10.00%)  2
Somnolence / depressed level of consciousness  1  1/20 (5.00%)  2
Syncope (fainting)  1  2/20 (10.00%)  2
Pain - Head / headache  1  6/20 (30.00%)  6
Psychiatric disorders   
Insomnia  1  5/20 (25.00%)  7
Confusion  1  2/20 (10.00%)  2
Mood Alteration - Agitation  1  1/20 (5.00%)  2
Mood Alteration - Anxiety  1  3/20 (15.00%)  3
Mood Alteration - Depression  1  1/20 (5.00%)  1
Psychosis (hallucinations / delusions)  1  2/20 (10.00%)  2
Renal and urinary disorders   
Hemorrhage, GU - Kidney  1  2/20 (10.00%)  2
Cystitis  1  2/20 (10.00%)  2
Renal Failure  1  1/20 (5.00%)  1
Urinary frequency / urgency  1  5/20 (25.00%)  6
Urinary retention (including neurogenic bladder)  1  1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)  1  1/20 (5.00%)  1
Edema: pulmonary  1  2/20 (10.00%)  2
Pulmonary / Upper Respiratory - Sore throat  1  1/20 (5.00%)  1
Bronchospasm, wheezing  1  1/20 (5.00%)  1
Cough  1  6/20 (30.00%)  6
Dyspnea (shortness of breath)  1  7/20 (35.00%)  11
Hypoxia  1  3/20 (15.00%)  3
Pulmonary / Upper Respiratory - Other  1  1/20 (5.00%)  1
Skin and subcutaneous tissue disorders   
Sweating (diaphoresis)  1  4/20 (20.00%)  4
Dermatology / Skin - Other  1  5/20 (25.00%)  5
Dry Skin  1  2/20 (10.00%)  2
Hair Loss / Alopecia (scalp or body)  1  1/20 (5.00%)  1
Pruritus / itching  1  1/20 (5.00%)  1
Rash / desquamation  1  5/20 (25.00%)  5
Ulceration  1  3/20 (15.00%)  3
Petechiae / purpura (hemorrhage / bleeding into skin or mucosa)  1  1/20 (5.00%)  1
Vascular disorders   
Hypotension  1  3/20 (15.00%)  5
Hot flashes / flushes  1  1/20 (5.00%)  1
Hemorrhage / Bleeding - Other  1  1/20 (5.00%)  1
Dermal change lymphedema, phlebolymphedema  1  3/20 (15.00%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
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: Mark Lanasa, MD, PhD
Organization: Duke University Medical Center
Phone: 919-286-6897
EMail: mark.lanasa@duke.edu
Layout table for additonal information
Responsible Party: David Rizzieri, Duke University
ClinicalTrials.gov Identifier: NCT00636155    
Other Study ID Numbers: Pro00001363
First Submitted: January 22, 2008
First Posted: March 14, 2008
Results First Submitted: May 29, 2012
Results First Posted: August 22, 2012
Last Update Posted: November 28, 2012