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

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01085201
• Collaborator: Brigham and Women's Hospital (Other), Boston Children's Hospital (Other), Washington University School of Medicine (Other), Medical College of Wisconsin (Other), Johns Hopkins University (Other), La Jolla Institute for Allergy & Immunology (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH), Astellas Pharma Global Development, Inc. (Industry)
• Enrollment: 39
• Locations: 7
• Arms: 5
• Duration (Months): 35
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Lexiscan	Phase 1

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety of Adenosine 2A Agonist Lexiscan in Children and Adults With Sickle Cell Disease
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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; Given as an infusion
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; Given as an infusion
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; Given as an infusion
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; Given as an infusion
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; Given as an infusion

Outcome Measures

Primary Outcome Measures

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

   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.

Secondary Outcome Measures

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

   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).

2. Pain Levels During a Vaso-occlusive Event in Children and Adults With SCD. [pre-drug to 54 hours]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Howard University Hospital	Washington	District of Columbia	United States
2	Johns Hopkins University	Baltimore	Maryland	United States
3	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
4	Childrens Hospital Boston	Boston	Massachusetts	United States	02115
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
6	Washington University	St. Louis	Missouri	United States
7	Blood Center of Wisconsin	Milwaukee	Wisconsin	United States

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• 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.

Investigators

• Principal Investigator: David Nathan, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David G. Nathan, MD, Professor of Pediatrics, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01085201
• Other Study ID Numbers: 09-308; 1RC2HL101367-01
• First Posted: Mar 11, 2010
• Last Update Posted: Mar 7, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by David G. Nathan, MD, Professor of Pediatrics, Dana-Farber Cancer Institute: lexiscan
• Additional relevant MeSH terms: Anemia, Sickle Cell; Regadenoson

Study Results

Participant Flow

Recruitment Details	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 Detail	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.

Arm/Group Title	Stage 1	Stage 2	Stage 2B	Stage 3	Stage 4
Arm/Group Description	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	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	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	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	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
Period Title: Overall Study
STARTED	18	7	5	6	3
COMPLETED	15	6	3	6	3
NOT COMPLETED	3	1	2	0	0

Baseline Characteristics

Arm/Group Title	Stage 1	Stage 2	Stage 2B	Stage 3	Stage 4	Total
Arm/Group Description	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	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	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	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	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 of all reporting groups
Overall Participants	15	6	3	6	3	33
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	3 100%	3 9.1%
Between 18 and 65 years	15 100%	6 100%	3 100%	6 100%	0 0%	30 90.9%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.71 (10.49)	33.84 (8.75)	23.68 (5.05)	31.61 (6.42)	16.77 (0.89)	30.9 (9.86)
Sex: Female, Male (Count of Participants)
Female	8 53.3%	3 50%	1 33.3%	3 50%	3 100%	18 54.5%
Male	7 46.7%	3 50%	2 66.7%	3 50%	0 0%	15 45.5%
Region of Enrollment (participants) [Number]
United States	15 100%	6 100%	3 100%	6 100%	3 100%	33 100%

Outcome Measures

1. Primary Outcome

Title	Dose Limiting Toxicities as a Measure of Whether Infusional Lexiscan is Safe in Individuals With SCD.
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Stage 1 - Dose Levels 0, 1 and 2	Stage 2 - Dose Level 2	Stage 2B - Dose Level 2	Stage 3 - Dose Level 2	Stage 4 - Dose Level 2
Arm/Group Description	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	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	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	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	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
Measure Participants	15	6	3	6	3
Number [number of DLT]	1	0	0	0	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The number of subjects was determined per protocol. Stage 1 was excluded as the goal was to determine the optimal markers for iNKT cells. Only 4 subjects were analyzed in Stage 2 because 24-hour samples were not obtained for 2 subjects. Stages 2b and 4 were not completely analyzed because these stages were completed early after studying 3 subjects.

Arm/Group Title	Stage 1 - Dose Levels 0, 1 and 2	Stage 2 - Dose Level 2	Stage 2B - Dose Level 2	Stage 3 - Dose Level 2	Stage 4 - Dose Level 2
Arm/Group Description	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	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	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	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	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
Measure Participants	0	4	0	6	0
Median (Standard Deviation) [percentage of change in activation]	-3 (0.30)	-48 (0.30)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The number of participants was determined per protocol following a 3+3 design. Stages 1, 2 and 2b were excluded because this outcome measure is specific to the experience of a vaso-occlusive event, which was studied in Stages 3 and 4.

Arm/Group Title	Stage 1	Stage 2	Stage 2B	Stage 3	Stage 4
Arm/Group Description	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	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	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	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	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
Measure Participants	0	0	0	6	3
Median (Standard Deviation) [units on a scale]	5.8 (0.8)	7.8 (1.1)

Adverse Events

Time Frame	3 years
Arm/Group Title	Stage 1 - Dose Levels 0, 1 and 2		Stage 2 - Dose Level 2		Stage 2B - Dose Level 2		Stage 3 - Dose Level 2		Stage 4 - Dose Level 2
Arm/Group Description	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		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		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		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		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
All Cause Mortality
	Stage 1 - Dose Levels 0, 1 and 2		Stage 2 - Dose Level 2		Stage 2B - Dose Level 2		Stage 3 - Dose Level 2		Stage 4 - Dose Level 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Stage 1 - Dose Levels 0, 1 and 2		Stage 2 - Dose Level 2		Stage 2B - Dose Level 2		Stage 3 - Dose Level 2		Stage 4 - Dose Level 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		2/6 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)
Blood and lymphatic system disorders
Sickle cell crisis with prolonged hospitalization - Grade 2	0/15 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Uncomplicated vaso-occlusive crisis requiring hospitalization - Grade 3	0/15 (0%)	0	1/6 (16.7%)	2	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Rib pain, leading to hospitalization - Grade 3	0/15 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	Stage 1 - Dose Levels 0, 1 and 2		Stage 2 - Dose Level 2		Stage 2B - Dose Level 2		Stage 3 - Dose Level 2		Stage 4 - Dose Level 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/6 (0%)		0/3 (0%)		0/6 (0%)		0/3 (0%)

Limitations/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.

More Information

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.