EL625 in Persistent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Leukemia, Lymphocytic, Chronic Clinical Trial

Official title:

A Phase II Study of EL625 in Patients in Persistent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00636155
• Other study ID #: Pro00001363
• Status: Terminated
• Phase: Phase 2
• First received: January 22, 2008
• Last updated: November 26, 2012
• Start date: February 2008
• Est. completion date: May 2012

Study information

• Verified date: November 2012
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: May 2012
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Small Lymphocytic

Intervention

Drug:
• cenersen sodium
2.4 mg/kg/day as a continuous infusion over 24 hours starting on day one and ending on day 4
• Rituximab
375 mg/m2 on day 2
• Cyclophosphamide
250 mg/m2 on days 2, 3, and 4
• Fludarabine
25 mg/m2 on days 2, 3, and 4

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
David Rizzieri	Eleos, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With an Overall Response (Complete Response + Partial Response)	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.	every 3 cycles	No
Secondary	Progression Free Survival	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.	5 years	No
Secondary	Overall Survival		5 years	No