Lymphoma, Small LymphocyticPhase 2NCT00636155
EL625 in Persistent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
A Phase 2 study testing cenersen sodium, Rituximab and Cyclophosphamide in people with Lymphoma, Small Lymphocytic and Leukemia, Lymphocytic, Chronic, run by David Rizzieri at 1 site in United States.
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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Small Lymphocytic, Leukemia, Lymphocytic, Chronic
- What is being tested?
- cenersen sodium, Rituximab and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to May 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Phase II Study of EL625 in Patients in Persistent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
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)
Read the 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.
- Being tested
- cenersen sodium, Rituximab, Cyclophosphamide, Fludarabine
- Keywords
- Small Lymphocytic Lymphoma, Chronic Lymphocytic Leukemia, EL625, cenersen
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cenersen sodiumDrug
Also called EL625
2.4 mg/kg/day as a continuous infusion over 24 hours starting on day one and ending on day 4
RituximabDrug
Also called Rituxan
375 mg/m2 on day 2
CyclophosphamideDrug
Also called Cytoxan
250 mg/m2 on days 2, 3, and 4
FludarabineDrug
Also called Fludara
25 mg/m2 on days 2, 3, and 4
| Study group | Role | What they receive |
|---|---|---|
| all patients | Experimental | EL625 combined with traditional chemotherapy (rituximab, fludarabine, and cyclophosphamide) Receives: Drug: cenersen sodium; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: every 3 cycles
Secondary outcomes (2)
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.
Measured: 5 years
Overall Survival
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2008 (estimated)
- Study startFeb 2008
- Primary completionAug 2011
- Study completionMay 2012
Why it stopped: funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lymphoma, Small LymphocyticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Rizzieri
- Sponsor type
- University, hospital or other
- Collaborators
- Eleos, Inc.
- Responsible party
- Sponsor-investigator, David Rizzieri, Duke University
- Investigators
- David Rizzieri, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00636155
- Sponsor's protocol ID
- Pro00001363
- Status last verified
- Nov 2012
- First submitted
- 22 Jan 2008
- Last updated
- 28 Nov 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of EL625 in Patients in Persistent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- ClinicalTrials.gov ID
- NCT00636155
- Acronym / sponsor ID
- Pro00001363
- Keywords
- Small Lymphocytic Lymphoma, Chronic Lymphocytic Leukemia, EL625, cenersen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: funding
- Enrolment
- 20 participants (actual)
- Lead sponsor
- David RizzieriUniversity, hospital or other
- Collaborators
- Eleos, Inc.
- Study start
- Feb 2008
- Primary completion
- Aug 2011 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 14 Mar 2008 (estimated)
- Results
- Posted 22 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| all patients | Experimental | Drug: cenersen sodium, Drug: Rituximab, Drug: Cyclophosphamide, Drug: FludarabineEL625 combined with traditional chemotherapy (rituximab, fludarabine, and cyclophosphamide) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cenersen sodiumAlso: EL6252.4 mg/kg/day as a continuous infusion over 24 hours starting on day one and ending on day 4 | Drug | all patients |
| RituximabAlso: Rituxan375 mg/m2 on day 2 | Drug | all patients |
| CyclophosphamideAlso: Cytoxan250 mg/m2 on days 2, 3, and 4 | Drug | all patients |
| FludarabineAlso: Fludara25 mg/m2 on days 2, 3, and 4 | Drug | all patients |
Primary outcome
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.
2 secondary outcomes
Progression Free Survival
Time frame: 5 years
Overall Survival
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Rizzieri, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cenersen sodium, Rituximab and Cyclophosphamide in people with Lymphoma, Small Lymphocytic and Leukemia, Lymphocytic, Chronic, run by David Rizzieri at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With an Overall Response (Complete Response + Partial Response) (time frame: every 3 cycles). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2012.