Adenosine 2A Agonist Lexiscan in Children and Adults With Sickle Cell Disease
Safety of Adenosine 2A Agonist Lexiscan in Children and Adults With Sickle Cell Disease
2 other identifiers
interventional
39
1 country
7
Brief Summary
Sickle cell disease (SCD) is an inherited blood disorder that causes the red blood cells to change their shape from a round shape to a half-moon/crescent or sickled shape. People who have SCD have a different type of protein that carries oxygen in their blood (hemoglobin) then people without SCD. This different type of hemoglobin makes the red blood cells change into a crescent shape under certain conditions. Sickle-shaped cells are a problem because they often get stuck in blood vessels blocking the flow of blood, and cause inflammation and injury to the important areas in the body. Lexiscan is drug that may prevent this inflammation and injury caused by the sickle shaped cells. This drug is approved by the FDA to be used as a fast infusion during a heart stress test in people who are unable to exercise enough to put stress on their heart by making it beat faster. Lexiscan has never been studied in patients with SCD and has never been given as a long infusion.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2010
Typical duration for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 10, 2010
CompletedFirst Posted
Study publicly available on registry
March 11, 2010
CompletedStudy Start
First participant enrolled
April 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2013
CompletedResults Posted
Study results publicly available
March 7, 2014
CompletedMarch 7, 2014
February 1, 2014
2.8 years
March 10, 2010
May 2, 2013
February 5, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Dose Limiting Toxicities as a Measure of Whether Infusional Lexiscan is Safe in Individuals With SCD.
Per protocol, Lexiscan was considered "safe" if well tolerated based on number of DLTs reported. Stage 1 of the study was a 3+3 dose escalation study. Three doses were tested: 0.24 mcg/kg/hr (dose level 0), 0.6 mcg/kg/hr (dose level 1), and 1.44 mcg/kg/hr (dose level 2). Dose escalation continued until 6 participants were treated at the maximum planned dose (dose level 2). We studied a total of 15 patients in Stage 1. In Stages 2 and 3, if at least 2/3 participants tolerated the dose, an additional 3 participants were studied. We studied 6 participants in each of stages 2 and 3. In stage 2b, Lexiscan was studied for a longer (48 hr) duration in 3 participants. In stage 4, Lexiscan was studied in 3 pediatric participants.
30 to 54 hours plus 30-day follow-up
Secondary Outcomes (2)
Percentage of Activated iNKT Cells and/or Activation Markers on iNKT Cells in Individuals With SCD.
pre-drug to 54 hours
Pain Levels During a Vaso-occlusive Event in Children and Adults With SCD.
pre-drug to 54 hours
Study Arms (5)
Stage 1
EXPERIMENTAL12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Stage 2
EXPERIMENTAL24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Stage 3
EXPERIMENTAL24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.
Stage 4
EXPERIMENTAL24-hour infusion to children with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Stage 2B
EXPERIMENTAL48-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AFTER STUDYING 3 PATIENTS BY AGREEMENT FROM THE FDA, IRB, AND DSMB. THIS STAGE IS CLOSED TO ACCRUAL.
Interventions
Eligibility Criteria
You may qualify if:
- Participants must have sickle cell anemia confirmed by hemoglobin analysis
- Participants must report that their pain is at baseline. Additionally, they cannot report an increase in dose or frequency of opioid use in the last 2 weeks prior to drug administration
- Age 21-70 years
- Participants must have the laboratory indices as outlined in the protocol
- Participants must have reliable IV access as determined by the investigator
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study.
- Participants must have sickle cell anemia confirmed by hemoglobin analysis
- Participant is admitted to the hospital for a pain episode
- Age 21-70 years
- Participants must have the laboratory indices as outlined in the protocol
- Participants must have reliable IV access as determined by the investigator
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
- Participants must have sickle cell disease confirmed by hemoglobin analysis
- Participant is admitted to the hospital for a pain episode
- Ages of assent (10 to 17 years at DFCI, but different depending on institution)
- +4 more criteria
You may not qualify if:
- Participants with a current physician diagnosis of asthma (within last 12 months), require continuous supplemental oxygen, or predicted or current use of some asthma medications.
- Participants with second- or third-degree AV block or sinus node dysfunction
- Have a history of bleeding diathesis
- Have a history of clinically overt stroke
- Have a history of severe hypertension not adequately controlled with anti-hypertensive medications
- Participants who are receiving chronic anti-coagulation or anti-platelet therapy
- Participants with a history of metastatic cancer
- Participants who have had a hospitalization or emergency room visit for any reason in the past 2 weeks
- Participants may not be receiving any other study agents or have received a study agent in the past 30 days
- Uncontrolled intercurrent illness
- Pregnant or breastfeeding women
- Participants with HIV
- Participants who have previously enrolled and received the investigational agent as part of this study
- Participants who are taking medications that may interact with the investigational agent
- Participants with a current physician diagnosis of asthma (within last 12 months), require continuous supplemental oxygen, or predicted or current use of some asthma medications.
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dana-Farber Cancer Institutelead
- Brigham and Women's Hospitalcollaborator
- Boston Children's Hospitalcollaborator
- Washington University School of Medicinecollaborator
- Medical College of Wisconsincollaborator
- Johns Hopkins Universitycollaborator
- La Jolla Institute for Allergy & Immunologycollaborator
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- Astellas Pharma Global Development, Inc.collaborator
Study Sites (7)
Howard University Hospital
Washington D.C., District of Columbia, United States
Johns Hopkins University
Baltimore, Maryland, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Childrens Hospital Boston
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Washington University
St Louis, Missouri, United States
Blood Center of Wisconsin
Milwaukee, Wisconsin, United States
Related Publications (1)
Field JJ, Lin G, Okam MM, Majerus E, Keefer J, Onyekwere O, Ross A, Campigotto F, Neuberg D, Linden J, Nathan DG. Sickle cell vaso-occlusion causes activation of iNKT cells that is decreased by the adenosine A2A receptor agonist regadenoson. Blood. 2013 Apr 25;121(17):3329-34. doi: 10.1182/blood-2012-11-465963. Epub 2013 Feb 1.
PMID: 23377438DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The highest dose we examined (dose level 2, 1.44 mcg/kg/hr) may not be the maximally tolerated dose. No toxicities definitely or probably attributable to the drug occurred, so it is possible that there is a higher dose that can be tolerated safely.
Results Point of Contact
- Title
- Dr. Joshua J. Field
- Organization
- BloodCenter of Wisconsin
Study Officials
- PRINCIPAL INVESTIGATOR
David Nathan, MD
Dana-Farber Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Pediatrics
Study Record Dates
First Submitted
March 10, 2010
First Posted
March 11, 2010
Study Start
April 1, 2010
Primary Completion
February 1, 2013
Study Completion
March 1, 2013
Last Updated
March 7, 2014
Results First Posted
March 7, 2014
Record last verified: 2014-02