Back to resultsA Study of the Effect of Vinca Alkaloids on c-Jun N-terminal Kinase (JNK) Phosphorylation in Patients With Chronic Lymphocytic Leukemia (CLL)
Primary Purpose
Chronic Lymphocytic Leukemia (CLL)
Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
vincristine
Sponsored by
About this trial
This is an interventional basic science trial for Chronic Lymphocytic Leukemia (CLL) focused on measuring vincristine, JNK, phosphorylation, cll, vinca alkaloid, apoptosis
Eligibility Criteria
Inclusion Criteria:
- Male or female, 18 years old or older.
- A diagnosis of Chronic Lymphocytic Leukemia(CLL) which is CD5/CD19/CD23 positive, confirmed by peripheral blood immunophenotyping and/or lymph node biopsy and immunophenotyping and/or bone marrow biopsy and immunophenotyping. CD23-negative CLL cases are eligible, however additional diagnostic confirmation should include absence of Cyclin D1 rearrangement [t(11;14)] as determined by standard laboratory methods (such as fluorescent in situ hybridization).
- Patients are planning to start chemotherapy for CLL recommended and prescribed by their primary oncologist.
- Peripheral blood lymphocyte count above 20,000/mm3
- Be able to provide written informed consent
Exclusion Criteria
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vincristine.
- Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Liver function test abnormalities of ≥ grade 3 (total bilirubin >3 ULN (upper limit of normal), AST> 5 ULN, ALT> 5 ULN) as per CTCAE 4.0 criteria, or direct bilirubin ≥ 3.0 mg/dL
- Pre-existing neuropathy grade 2 or greater as per CTCAE 4.0 criteria (moderate symptoms limiting instrumental activities of daily living - ADLs)
- Patients who are pregnant or planning to become pregnant during their participation in the study.
Sites / Locations
- Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Vincrisitne 2mg
Arm Description
Single Arm study: Vincristine 2mg administered IV by infusion over 5 minutes.
Outcomes
Primary Outcome Measures
c-Jun N-terminal Kinase (JNK) activation
blood draws are collected pre-vincristine and at 10 minutes,1,2,4,and 6 hours post vincristine.
Secondary Outcome Measures
Full Information
NCT ID
NCT01463852
First Posted
October 31, 2011
Last Updated
May 8, 2015
Sponsor
Dartmouth-Hitchcock Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT01463852
Brief Title
A Study of the Effect of Vinca Alkaloids on c-Jun N-terminal Kinase (JNK) Phosphorylation in Patients With Chronic Lymphocytic Leukemia (CLL)
Official Title
A Study of the Effect of Vinca Alkaloids on c-Jun N-terminal Kinase (JNK) Phosphorylation Status in Patients With Chronic Lymphocytic Leukemia (CLL)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Terminated
Why Stopped
Enrollment underperformance.
Study Start Date
October 2012 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dartmouth-Hitchcock Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In this proof-of-principle study, patients with chronic lymphocytic leukemia (CLL), who are scheduled to initiate treatment per the recommendations of their primary oncologist, will receive a single dose of vincristine 2 milligrams (mg). The objective is to determine if this single dose will induce rapid cell death in isolated CLL cells.
Vincristine 2 mg will be administered to the participants intravenously over 5 minutes. Blood samples will be collected from an intravenous line inserted into the contralateral limb to that where the vincristine was given, at time zero (pre-vincristine treatment), immediately after vincristine administration (within 2-10 minutes upon completion of administration) and at 1, 2, 4 and 6 hours post-vincristine treatment. Patients will then at a later date receive chemotherapy treatment as prescribed by their primary oncologist.
Within 7 days of vincristine administration, participants will receive a phone call from the research nurse to discuss potential toxicities. At the time of the initiation of standard chemotherapy treatment, the Principal Investigator will also meet with the participant to collect information regarding adverse events.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia (CLL)
Keywords
vincristine, JNK, phosphorylation, cll, vinca alkaloid, apoptosis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vincrisitne 2mg
Arm Type
Experimental
Arm Description
Single Arm study: Vincristine 2mg administered IV by infusion over 5 minutes.
Intervention Type
Drug
Intervention Name(s)
vincristine
Intervention Description
Vincristine 2mg will be administered one time to participants. Blood samples will be collected pre and post dose.
Primary Outcome Measure Information:
Title
c-Jun N-terminal Kinase (JNK) activation
Description
blood draws are collected pre-vincristine and at 10 minutes,1,2,4,and 6 hours post vincristine.
Time Frame
Change in JNK activation from baseline up to 6 hours post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, 18 years old or older.
A diagnosis of Chronic Lymphocytic Leukemia(CLL) which is CD5/CD19/CD23 positive, confirmed by peripheral blood immunophenotyping and/or lymph node biopsy and immunophenotyping and/or bone marrow biopsy and immunophenotyping. CD23-negative CLL cases are eligible, however additional diagnostic confirmation should include absence of Cyclin D1 rearrangement [t(11;14)] as determined by standard laboratory methods (such as fluorescent in situ hybridization).
Patients are planning to start chemotherapy for CLL recommended and prescribed by their primary oncologist.
Peripheral blood lymphocyte count above 20,000/mm3
Be able to provide written informed consent
Exclusion Criteria
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
Patients who are receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to vincristine.
Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Liver function test abnormalities of ≥ grade 3 (total bilirubin >3 ULN (upper limit of normal), AST> 5 ULN, ALT> 5 ULN) as per CTCAE 4.0 criteria, or direct bilirubin ≥ 3.0 mg/dL
Pre-existing neuropathy grade 2 or greater as per CTCAE 4.0 criteria (moderate symptoms limiting instrumental activities of daily living - ADLs)
Patients who are pregnant or planning to become pregnant during their participation in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexey V Danilov, MD
Organizational Affiliation
Dartmouth-Hitchcock Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of the Effect of Vinca Alkaloids on c-Jun N-terminal Kinase (JNK) Phosphorylation in Patients With Chronic Lymphocytic Leukemia (CLL)
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