A Study of the Effect of Vinca Alkaloids on c-Jun N-terminal Kinase (JNK) Phosphorylation in Patients With Chronic Lymphocytic Leukemia (CLL)

This study has been terminated.
(Enrollment underperformance.)
Sponsor:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT01463852
First received: October 31, 2011
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia (CLL)
Drug: vincristine
Phase 0

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
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)

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • c-Jun N-terminal Kinase (JNK) activation [ Time Frame: Change in JNK activation from baseline up to 6 hours post dose ] [ Designated as safety issue: No ]
    blood draws are collected pre-vincristine and at 10 minutes,1,2,4,and 6 hours post vincristine.


Enrollment: 11
Study Start Date: October 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vincrisitne 2mg
Single Arm study: Vincristine 2mg administered IV by infusion over 5 minutes.
Drug: vincristine
Vincristine 2mg will be administered one time to participants. Blood samples will be collected pre and post dose.

  Eligibility

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

Inclusion Criteria:

  1. Male or female, 18 years old or older.
  2. 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).
  3. Patients are planning to start chemotherapy for CLL recommended and prescribed by their primary oncologist.
  4. Peripheral blood lymphocyte count above 20,000/mm3
  5. Be able to provide written informed consent

Exclusion Criteria

  1. 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.
  2. Patients who are receiving any other investigational agents.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to vincristine.
  4. 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.
  5. 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
  6. Pre-existing neuropathy grade 2 or greater as per CTCAE 4.0 criteria (moderate symptoms limiting instrumental activities of daily living - ADLs)
  7. Patients who are pregnant or planning to become pregnant during their participation in the study.
  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: NCT01463852

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Alexey V Danilov, MD Dartmouth-Hitchcock Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT01463852     History of Changes
Other Study ID Numbers: D11199
Study First Received: October 31, 2011
Last Updated: February 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
vincristine
JNK
phosphorylation
cll
vinca alkaloid
apoptosis

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Vinca Alkaloids
Vincristine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on August 01, 2014