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CompletedNCT01085201Updated Mar 7, 2014Results posted

Adenosine 2A Agonist Lexiscan in Children and Adults With Sickle Cell Disease

A Phase 1 interventional study of Lexiscan in Sickle Cell Disease, sponsored by Dana-Farber Cancer Institute. Completed at 7 sites in United States. Open to participants aged 10 Years to 70 Years. Per ClinicalTrials.gov, last updated 2014-03-07.

Sponsored by Dana-Farber Cancer Institute · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
39
Allocation
Non-randomized
Ages
10 Years to 70 Years
Sex
All
01

Study 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.

Read the detailed description
  • In this research study we are looking for the highest dose of Lexiscan that can be given safely to patients with SCD. There are 4 stages to this study. Each stage will look for the highest dose that can be given safely in the following situations: Stage 1: Lexiscan will be given through a 12 hours infusion to adults with SCD who are not having a pain crisis. Stage 2: Lexiscan will be given through a 24 hour infusion to adults with SCD who are not having a pain crisis. Stage 2b: Lexiscan will be given through a 48 hour infusion to adults with SCD who are not having a pain crisis. Stage 3: Lexiscan will be given through a 24 hour infusion to adults with SCD who are having a pain crisis. Stage 4: Lexiscan will be given through a 24 hour infusion to children with SCD who are having a pain crisis. Stages 1-3 are now complete and closed to accrual. The study is now open to children ages 10-17 with SCD pain crisis (stage 4) only.
  • When participants sign the consent form, they will be told what stage they will join.
  • Participants in Stages 1, 2, and 2b will be given an infusion of the study drug at the time when they do not have a pain crisis. The infusion for Stage 1 participants will be 12 hours long, followed by a 6-hour observation period. The infusion for Stage 2 will be 24 hours long, followed by a 6-hour observation period. The infusion for Stage 2b will be 48 hours long, followed by a 6-hour observation period.
  • Participants in Stages 3 and 4 will be given one infusion of the study drug when they are admitted to the hospital for a pain crisis. The infusion will be 24 hours long, followed by a 6-hour observation period. During the infusion, they will receive standard treatment for their pain crisis.
  • Before the infusion the following procedures will be performed: Pulmonary function test (optional, Stage 1 only), blood test and vital signs.
  • During the infusion the following procedures will be performed: heart rate and amount of oxygen in the blood will be monitored continuously, blood tests and blood pressure.
  • During the observation period immediately following the infusion the following procedures will be performed: heart rate and amount of oxygen in the blood will be monitored continuously, blood tests, blood pressure and Pulmonary Function test (optional, Stage 1 only).
02

Conditions studied

  • Sickle Cell Disease

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Keywords

  • lexiscan
03

In context

Anemia, Sickle Cell

1,103 studies on the registry are indexed under Anemia, Sickle Cell; 235 are open to participants now.

This study's enrollment of 39 is close to the median of 40 across 750 interventional studies indexed under Anemia, Sickle Cell.

Browse Anemia, Sickle Cell studies →

Lead sponsor

Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.

Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
10 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria Stage I/II/IIb: (COMPLETE AND CLOSED TO ACCRUAL)

  • 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.

Inclusion Criteria Stage III: (COMPLETE AND CLOSED TO ACCRUAL)

  • 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

Inclusion Criteria Stage IV: (open, still accruing volunteers)

  • 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)
  • Participants must have the laboratory indices as outlined in the protocol
  • Participants must have reliable IV access as determined by the investigator
  • Participants and parents must have the ability to understand and the willingness to sign a written informed consent and assent document
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria Stage I/II/IIb: (COMPLETE AND CLOSED TO ACCRUAL)

  • 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

Exclusion Criteria Stage III: (COMPLETE AND CLOSED TO ACCRUAL)

  • 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 may not be receiving any other study agents or have received a study agent in the past 30 days

Exclusion Criteria Stage IV: (open, still accruing volunteers)

  • 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 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 may not be receiving any other study agents or have received a study agent in the past 30 days
  • 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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
39 participants (actual)

Study arms

  • Experimental
    Stage 1

    12-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.

    Drug: Lexiscan

  • Experimental
    Stage 2

    24-hour infusion to adults with SCD who are not having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.

    Drug: Lexiscan

  • Experimental
    Stage 3

    24-hour infusion to adults with SCD who are having a pain crisis. THIS STAGE IS COMPLETE AND CLOSED TO ACCRUAL.

    Drug: Lexiscan

  • Experimental
    Stage 4

    24-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.

    Drug: Lexiscan

  • Experimental
    Stage 2B

    48-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.

    Drug: Lexiscan

Interventions

  • DrugLexiscan

    Given as an infusion

06

What researchers measure

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.

    Time frame: 30 to 54 hours plus 30-day follow-up

Secondary outcomes

  1. Percentage of Activated iNKT Cells and/or Activation Markers on iNKT Cells in Individuals With SCD.

    Percentage of activated iNKT cells after receiving a 24-hour infusion of Lexiscan was compared to pre-drug. iNKT cell activation was evaluated using antibodies targeting the p65 subunit of nuclear factor-kappa B (phospho-NF-kB p65). Measures are given as percentage of change in phospho-NF-kB p65 activation in iNKT cells compared to pre-drug after a 24-hour infusion. iNKT cell activation in Stages 1, 2b, and 4 was not analyzed (see analysis population description).

    Time frame: pre-drug to 54 hours

  2. Pain Levels During a Vaso-occlusive Event in Children and Adults With SCD.

    Pain was measured using a standardized pain scale. The scale is a 10-cm visual analogue scale (10 cm-long line printed on white paper), where 0 is no pain and 10 is maximum pain. Participants were asked to indicate their pain level by marking on the line prior to each blood draw.

    Time frame: pre-drug to 54 hours

07

Results

Posted Mar 7, 2014
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.

Participant flow

Recruitment began on 4/19/10 and ceased completely on 3/26/13. In Stages 1, 2 and 2b, patients were recruited from the medical clinic. For Stages 3 and 4, in which subjects were treated during a pain crisis hospitalization, patients were first informed about the study in clinic, and reminded about the study after being admitted.

Participant flow — Overall Study
MilestoneStage 1Stage 2Stage 2BStage 3Stage 4
Started187563
Completed156363
Not completed31200
Withdrew: Scheduling conflict10100
Withdrew: Unknown- no study drug20000
Withdrew: Fond ineligible after consent01100

Outcome measures

PrimaryDose 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.

Time frame:
30 to 54 hours plus 30-day follow-up
Reported as:
Number · number of DLT
Dose Limiting Toxicities as a Measure of Whether Infusional Lexiscan is Safe in Individuals With SCD.
number of DLTStage 1 - Dose Levels 0, 1 and 2Stage 2 - Dose Level 2Stage 2B - Dose Level 2Stage 3 - Dose Level 2Stage 4 - Dose Level 2
Dose Limiting Toxicities as a Measure of Whether Infusional Lexiscan is Safe in Individuals With SCD.10000
SecondaryPercentage of Activated iNKT Cells and/or Activation Markers on iNKT Cells in Individuals With SCD.

Percentage of activated iNKT cells after receiving a 24-hour infusion of Lexiscan was compared to pre-drug. iNKT cell activation was evaluated using antibodies targeting the p65 subunit of nuclear factor-kappa B (phospho-NF-kB p65). Measures are given as percentage of change in phospho-NF-kB p65 activation in iNKT cells compared to pre-drug after a 24-hour infusion. iNKT cell activation in Stages 1, 2b, and 4 was not analyzed (see analysis population description).

Time frame:
pre-drug to 54 hours
Reported as:
Median · percentage of change in activation
Percentage of Activated iNKT Cells and/or Activation Markers on iNKT Cells in Individuals With SCD.
percentage of change in activationStage 1 - Dose Levels 0, 1 and 2Stage 2 - Dose Level 2Stage 2B - Dose Level 2Stage 3 - Dose Level 2Stage 4 - Dose Level 2
Percentage of Activated iNKT Cells and/or Activation Markers on iNKT Cells in Individuals With SCD.—-3 ± 0.30—-48 ± 0.30—
SecondaryPain Levels During a Vaso-occlusive Event in Children and Adults With SCD.

Pain was measured using a standardized pain scale. The scale is a 10-cm visual analogue scale (10 cm-long line printed on white paper), where 0 is no pain and 10 is maximum pain. Participants were asked to indicate their pain level by marking on the line prior to each blood draw.

Time frame:
pre-drug to 54 hours
Reported as:
Median · units on a scale
Pain Levels During a Vaso-occlusive Event in Children and Adults With SCD.
units on a scaleStage 1Stage 2Stage 2BStage 3Stage 4
Pain Levels During a Vaso-occlusive Event in Children and Adults With SCD.———5.8 ± 0.87.8 ± 1.1

Adverse events

Collected over 3 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Stage 1 - Dose Levels 0, 1 and 2—0/15 (0%)0/15 (0%)
Stage 2 - Dose Level 2—2/6 (33.3%)0/6 (0%)
Stage 2B - Dose Level 2—0/3 (0%)0/3 (0%)
Stage 3 - Dose Level 2—1/6 (16.7%)0/6 (0%)
Stage 4 - Dose Level 2—0/3 (0%)0/3 (0%)
Most frequent serious events
Most frequent serious events
EventStage 1 - Dose Levels 0, 1 and 2Stage 2 - Dose Level 2Stage 2B - Dose Level 2Stage 3 - Dose Level 2Stage 4 - Dose Level 2
Sickle cell crisis with prolonged hospitalization - Grade 2Blood and lymphatic system disorders0/151/60/30/60/3
Uncomplicated vaso-occlusive crisis requiring hospitalization - Grade 3Blood and lymphatic system disorders0/151/60/31/60/3
Rib pain, leading to hospitalization - Grade 3Musculoskeletal and connective tissue disorders0/150/60/31/60/3

Baseline characteristics

The number of participants was determined per protocol following a 3+3 design. In Stages 2b and 4, we received permission from the FDA, IRB, and DSMB to study only 3 subjects because we did not observe any prior DLT. One patient enrolled in Stage 2b withdrew consent during the infusion due to an unrelated toothache, and was excluded from analysis.

Age, Categorical
Age, Categorical(Participants)Stage 1Stage 2Stage 2BStage 3Stage 4Total
<=18 years000033
Between 18 and 65 years15636030
>=65 years000000
Age, Continuous
Age, Continuous(years)Stage 1Stage 2Stage 2BStage 3Stage 4Total
Mean33.71 ± 10.4933.84 ± 8.7523.68 ± 5.0531.61 ± 6.4216.77 ± 0.8930.9 ± 9.86
Sex: Female, Male
Sex: Female, Male(Participants)Stage 1Stage 2Stage 2BStage 3Stage 4Total
Female8313318
Male7323015
Region of Enrollment
Region of Enrollment(participants)Stage 1Stage 2Stage 2BStage 3Stage 4Total
United States15636333
08

Study locations

7 sites
  • Howard University Hospital
    Washington, 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
09

References and documents

Publications

  • 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. PubMed 23377438 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 7, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01085201
Lead sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Boston Children's Hospital, Washington University School of Medicine, Medical College of Wisconsin, Johns Hopkins University, La Jolla Institute for Allergy & Immunology, National Heart, Lung, and Blood Institute (NHLBI), Astellas Pharma Global Development, Inc.
Responsible party
David G. Nathan, MD (Professor of Pediatrics, Dana-Farber Cancer Institute) — Principal investigator
First posted
Mar 11, 2010
Start date
Apr 2010
Primary completion
Feb 2013
Completion
Mar 2013
Results posted
Mar 7, 2014
Last update
Mar 7, 2014

Study contacts

David Nathan, MD
principal investigator · Dana-Farber Cancer Institute

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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