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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

Tracking Information
First Submitted Date  ICMJE January 22, 2008
First Posted Date  ICMJE March 14, 2008
Results First Submitted Date  ICMJE May 29, 2012
Results First Posted Date  ICMJE August 22, 2012
Last Update Posted Date November 28, 2012
Study Start Date  ICMJE February 2008
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2012)
Number of Patients With an Overall Response (Complete Response + Partial Response) [ Time Frame: every 3 cycles ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 13, 2008)
Response rate [ Time Frame: every 3 cycles ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2012)
  • Progression Free Survival [ Time Frame: 5 years ]
    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.
  • Overall Survival [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2008)
  • Toxicity [ Time Frame: every cycle ]
  • Evaluate survival, progression free survival and event free survival [ Time Frame: 5 years ]
  • Evaluate changes in apoptosis and cellular repair regulators [ Time Frame: post-treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE EL625 in Persistent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Official Title  ICMJE A Phase II Study of EL625 in Patients in Persistent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Brief Summary The purpose of this research study is to see if the investigational drug EL625, when combined with traditional chemotherapy (rituximab, fludarabine, and cyclophosphamide), is effective in Persistent Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)
Detailed Description

Chronic lymphocytic leukemia (CLL) and small B-cell lymphocytic lymphoma (SLL) are thought to be different manifestations of the same disease. Treatment options for CLL/SLL range from a watch and wait approach to bone marrow transplant. Currently there is no consensus on the best treatment regimen and new approaches to treatment are needed.

EL625 is a 20-mer antisense molecule which binds to a coding region of exon 10 in p53 RNA transcripts. It can bind to both mutant and wild type p53. p53 is involved in regulating apoptosis and DNA repair in cells. When genetic damage occurs p53 is upregulated. As the expression of p53 increases in normal cells they are more likely to undergo apoptosis rather than cell cycle arrest and DNA repair. However in malignant cells, for a given level of DNA damage they are more likely to undergo cell cycle arrest and repair rather than apoptosis. Because EL625 is theorized to increase response to chemotherapy, we propose adding EL625 to a combination of fludarabine, cyclophosphamide and rituximab.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphoma, Small Lymphocytic
  • Leukemia, Lymphocytic, Chronic
Intervention  ICMJE
  • Drug: cenersen sodium
    2.4 mg/kg/day as a continuous infusion over 24 hours starting on day one and ending on day 4
    Other Name: EL625
  • Drug: Rituximab
    375 mg/m2 on day 2
    Other Name: Rituxan
  • Drug: Cyclophosphamide
    250 mg/m2 on days 2, 3, and 4
    Other Name: Cytoxan
  • Drug: Fludarabine
    25 mg/m2 on days 2, 3, and 4
    Other Name: Fludara
Study Arms  ICMJE Experimental: all patients
EL625 combined with traditional chemotherapy (rituximab, fludarabine, and cyclophosphamide)
Interventions:
  • Drug: cenersen sodium
  • Drug: Rituximab
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 26, 2010)
20
Original Estimated Enrollment  ICMJE
 (submitted: March 13, 2008)
37
Actual Study Completion Date  ICMJE May 2012
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with a diagnosis of CLL/SLL who have received at least one prior treatment regimen and have persistent disease (i.e. any evidence of active disease). Patients with a chromosome 17 abnormality or a p53 mutation of any type may be enrolled without having received prior treatment.
  • Patients must be 18 years of age or older.
  • Patient has an estimated or measured creatinine clearance ≥30 ml/min at study enrollment.
  • AST, ALT, total bilirubin < than 2.5 times the upper limit of normal.
  • WBC > 1.5; ANC >500; Plt >50,000 unless documented as due to disease
  • ECOG performance status of 0-2.
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for 2 weeks after administration of the study drug.
  • Male subject agrees to use an acceptable method for contraception for the duration of the study therapy and for 2 weeks after administration of study drug.

Exclusion Criteria:

  • Female who is pregnant or lactating.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Patients with another malignancy within the last three years (from documentation of remission) other than basal or squamous cell skin cancer, resected early stage prostate cancer not requiring systemic treatment or CIS of the cervix or fully treated early stage prostate cancer.
  • Significant cardiac or vascular events within 6 months: acute MI, unstable angina, severe peripheral vascular disease (ischemic pain at rest class 3 or worse, non-healing ulcers/wounds, congestive heart failure (NYHA class ≥ 2), uncontrolled cardiac arrhythmias, and disseminated intravascular coagulation.
  • Patients who are unable to refrain from taking acetaminophen
  • Investigational agent within 14 days of enrolling on the study.
  • Patients unable or unwilling to refrain from antioxidants including vitamin A, vitamin C, vitamin E, lycopene, lutein, grape seed extract, pycnogenol, green tea extract, and the like.
  • Patients who have received a prior allogenic stem cell transplant and have at least 2.5% donor cells still evident on engraftment studies.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00636155
Other Study ID Numbers  ICMJE Pro00001363
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party David Rizzieri, Duke University
Study Sponsor  ICMJE David Rizzieri
Collaborators  ICMJE Eleos, Inc.
Investigators  ICMJE
Principal Investigator: David Rizzieri, MD Duke University
PRS Account Duke University
Verification Date November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP