EL625 in Persistent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This study has been terminated.
(funding)
Sponsor:
Collaborator:
Eleos, Inc.
Information provided by (Responsible Party):
David Rizzieri, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00636155
First received: January 22, 2008
Last updated: November 26, 2012
Last verified: November 2012
  Purpose

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)


Condition Intervention Phase
Lymphoma, Small Lymphocytic
Leukemia, Lymphocytic, Chronic
Drug: cenersen sodium
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Fludarabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of EL625 in Patients in Persistent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Number of Patients With an Overall Response (Complete Response + Partial Response) [ Time Frame: every 3 cycles ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: February 2008
Study Completion Date: May 2012
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: all patients
EL625 combined with traditional chemotherapy (rituximab, fludarabine, and cyclophosphamide)
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00636155

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
David Rizzieri
Eleos, Inc.
Investigators
Principal Investigator: David Rizzieri, MD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: David Rizzieri, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00636155     History of Changes
Other Study ID Numbers: Pro00001363
Study First Received: January 22, 2008
Results First Received: May 29, 2012
Last Updated: November 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia
EL625
cenersen

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Rituximab
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014