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

NCT01463852 | Terminated Early Phase 1 DMC

• 1 other identifier: D11199
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Lymphocytic Leukemia (CLL)

Keywords

vincristine; JNK; phosphorylation; cll; vinca alkaloid; apoptosis

Outcome Measures

Primary Outcomes (1)

• 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.

  Change in JNK activation from baseline up to 6 hours post dose

Study Arms (1)

Vincrisitne 2mg

EXPERIMENTAL

Single Arm study: Vincristine 2mg administered IV by infusion over 5 minutes.

Drug: vincristine

Interventions

vincristine DRUG

Vincristine 2mg will be administered one time to participants. Blood samples will be collected pre and post dose.

Vincrisitne 2mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, B-Cell

Interventions

Vincristine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Alexey V Danilov, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2011
• First Posted: November 2, 2011
• Study Start: October 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 12, 2015

Record last verified: 2014-02

Locations

US (1)