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

• 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).

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