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

This study has been completed.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Children's Hospital Boston
Washington University School of Medicine
Medical College of Wisconsin
Johns Hopkins University
LaJolla Institute for Allergy and Immunology
Astellas Pharma Global Development, Inc.
Information provided by (Responsible Party):
David G. Nathan, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01085201
First received: March 10, 2010
Last updated: February 5, 2014
Last verified: February 2014
Results First Received: May 2, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Sickle Cell Disease
Intervention: Drug: Lexiscan

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients who were assigned to Stages 1, 2 or 2b, in which subjects were studied at baseline (i.e. not in pain crisis), could be excluded if they experienced a pain crisis in the interim period between enrollment and their scheduled study date.

Reporting Groups
  Description
Stage 1

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

Lexiscan : Given as an infusion

Stage 2

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

Lexiscan : Given as an infusion

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.

Lexiscan : Given as an infusion

Stage 3

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

Lexiscan : Given as an infusion

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.

Lexiscan : Given as an infusion


Participant Flow:   Overall Study
    Stage 1     Stage 2     Stage 2B     Stage 3     Stage 4  
STARTED     18     7     5     6     3  
COMPLETED     15     6     3     6     3  
NOT COMPLETED     3     1     2     0     0  
Scheduling conflict                 1                 0                 1                 0                 0  
Unknown- no study drug                 2                 0                 0                 0                 0  
Fond ineligible after consent                 0                 1                 1                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Stage 1

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

Lexiscan : Given as an infusion

Stage 2

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

Lexiscan : Given as an infusion

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.

Lexiscan : Given as an infusion

Stage 3

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

Lexiscan : Given as an infusion

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.

Lexiscan : Given as an infusion

Total Total of all reporting groups

Baseline Measures
    Stage 1     Stage 2     Stage 2B     Stage 3     Stage 4     Total  
Number of Participants  
[units: participants]
  15     6     3     6     3     33  
Age  
[units: participants]
           
<=18 years     0     0     0     0     3     3  
Between 18 and 65 years     15     6     3     6     0     30  
>=65 years     0     0     0     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  33.71  ± 10.49     33.84  ± 8.75     23.68  ± 5.05     31.61  ± 6.42     16.77  ± 0.89     30.9  ± 9.86  
Gender  
[units: participants]
           
Female     8     3     1     3     3     18  
Male     7     3     2     3     0     15  
Region of Enrollment  
[units: participants]
           
United States     15     6     3     6     3     33  



  Outcome Measures
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1.  Primary:   Dose Limiting Toxicities as a Measure of Whether Infusional Lexiscan is Safe in Individuals With SCD.   [ Time Frame: 30 to 54 hours plus 30-day follow-up ]

2.  Secondary:   Percentage of Activated iNKT Cells and/or Activation Markers on iNKT Cells in Individuals With SCD.   [ Time Frame: pre-drug to 54 hours ]

3.  Secondary:   Pain Levels During a Vaso-occlusive Event in Children and Adults With SCD.   [ Time Frame: pre-drug to 54 hours ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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:  
Name/Title: Dr. Joshua J. Field
Organization: BloodCenter of Wisconsin
phone: 414-937-3848
e-mail: joshua.field@bcw.edu


No publications provided by Dana-Farber Cancer Institute

Publications automatically indexed to this study:

Responsible Party: David G. Nathan, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01085201     History of Changes
Other Study ID Numbers: 09-308, 1RC2HL101367-01
Study First Received: March 10, 2010
Results First Received: May 2, 2013
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration