Bone Marrow Transplantation, Hemoglobinopathies, SCALLOP (SCALLOP)

• ClinicalTrials.gov Identifier: NCT00578344
• Recruitment Status: Terminated
• First Posted: December 21, 2007
• Results First Posted: July 31, 2020
• Last Update Posted: July 31, 2020
• Sponsor: Tami D. John
• Collaborators: Baylor College of Medicine; The Methodist Hospital Research Institute
• Information provided by (Responsible Party): Tami D. John, Baylor College of Medicine

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Sickle Cell Disease; Hemoglobin SC
• Interventions: Drug: Busulfan; Biological: Campath 1H; Drug: Cyclophosphamide and MESNA
• Enrollment: 8

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Allogeneic BMT/SCT Transplant
Arm/Group Description	Busulfan, Campath 1H, Cyclophosphamide and MESNA: Bone marrow infusion with pre-meds as per SOPs to take place on Day 0. Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest. Busulfan: Starting Day -9 / Busulfan 4.0 mg/kg/day IV divided into four doses daily for four days; total dose = 16 mg/kg. Campath 1H: Day -5 through Day -2; Campath-1H dosed as per institutional guidelines. Cyclophosphamide and MESNA: Day -5 through Day -2; Cyclophosphamide 50 mg/kg + MESNA.
Period Title: Overall Study
Started	8
Completed	6
Not Completed	2
Reason Not Completed
Insurance problems	1
Graft failure	1

Baseline Characteristics

Arm/Group Title		Allogeneic BMT/SCT Transplant
Arm/Group Description		Busulfan, Campath 1H, Cyclophosphamide and MESNA: Bone marrow infusion with pre-meds as per SOPs to take place on Day 0. Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest. Busulfan: Starting Day -9 / Busulfan 4.0 mg/kg/day IV divided into four doses daily for four days; total dose = 16 mg/kg. Campath 1H: Day -5 through Day -2; Campath-1H dosed as per institutional guidelines. Cyclophosphamide and MESNA: Day -5 through Day -2; Cyclophosphamide 50 mg/kg + MESNA.
Overall Number of Baseline Participants		8
Baseline Analysis Population Description		All participants underwent allogeneic bone marrow transplantation from human leukocyte antigen (HLA) identical related donors with hemoglobinopathies.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	8 participants
		8.5; (4 to 14)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	Female	4 50.0%
	Male	4 50.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	Hispanic or Latino	1 12.5%
	Not Hispanic or Latino	7 87.5%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	6 75.0%
	White	2 25.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Evaluated for Evidence of Recovery of Organ Function Measured Via MRI or PET Scan.
Description	Assess Number of participants that recovered organ function diagnosed with sickle cell disease (SCD) or sickle hemoglobin variants after undergoing allogeneic SCT/BMT from HLA genotype identical donors.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

Out of eight participants who underwent bone marrow transplant, six participants with positron emission tomography (PET) or magnetic resonance imaging (MRI) at the time of assessment were included in the analysis. The other two were inevaluable due to graft failure or no PET or MRI at the time of assessment. Data were collected at 1 year only.

Arm/Group Title	Allogeneic BMT/SCT Transplant
Arm/Group Description:	Busulfan, Campath 1H, Cyclophosphamide and MESNA: Bone marrow infusion with pre-meds as per SOPs to take place on Day 0. Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest. Busulfan: Starting Day -9 / Busulfan 4.0 mg/kg/day IV divided into four doses daily for four days; total dose = 16 mg/kg. Campath 1H: Day -5 through Day -2; Campath-1H dosed as per institutional guidelines. Cyclophosphamide and MESNA: Day -5 through Day -2; Cyclophosphamide 50 mg/kg + MESNA.
Overall Number of Participants Analyzed	6
Measure Type: Count of Participants; Unit of Measure: Participants
Stable	4 66.7%
Progressive	2 33.3%

2. Primary Outcome

Title	Number of Participants With Pre and Post Transplant PET Scan to Assess Organ Recovery Based on Rate of Acquisition.
Description	Number of participants that did or did not have pre- and post- PET scans.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

All participants who underwent allogeneic bone marrow transplantation from human leukocyte antigen (HLA) identical related donors with hemoglobinopathies were included in the analysis.

Arm/Group Title	Allogeneic BMT/SCT Transplant
Arm/Group Description:	Busulfan, Campath 1H, Cyclophosphamide and MESNA: Bone marrow infusion with pre-meds as per SOPs to take place on Day 0. Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest. Busulfan: Starting Day -9 / Busulfan 4.0 mg/kg/day IV divided into four doses daily for four days; total dose = 16 mg/kg. Campath 1H: Day -5 through Day -2; Campath-1H dosed as per institutional guidelines. Cyclophosphamide and MESNA: Day -5 through Day -2; Cyclophosphamide 50 mg/kg + MESNA.
Overall Number of Participants Analyzed	8
Measure Type: Count of Participants; Unit of Measure: Participants
No pre and post PET scan	6 75.0%
Pre and post PET scan	2 25.0%

3. Primary Outcome

Title	Number of Participants With Immune Response to Immunization After BMT in Participants With SCD, Hemoglobin SC, or Hemoglobin Sb0/+.
Description	Vaccine response will be measured via a humoral immunity panel evaluating streptococcus pneumonia IgG antibodies (microgram/mL). Panels are obtained pre and 1+ month post vaccination. Standard recommendations define a normal responder as having >4 fold increase in antibody level in 50-70% of the serotypes found in the vaccine.
Time Frame	up to 12 months

Outcome Measure Data

Analysis Population Description

Out of eight participants who underwent bone marrow transplant, seven participants engrafted were included in the analysis. The other participant was excluded because he/she did not engraft and received a second transplant.

Arm/Group Title	Allogeneic BMT/SCT Transplant
Arm/Group Description:	Busulfan, Campath 1H, Cyclophosphamide and MESNA: Bone marrow infusion with pre-meds as per SOPs to take place on Day 0. Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest. Busulfan: Starting Day -9 / Busulfan 4.0 mg/kg/day IV divided into four doses daily for four days; total dose = 16 mg/kg. Campath 1H: Day -5 through Day -2; Campath-1H dosed as per institutional guidelines. Cyclophosphamide and MESNA: Day -5 through Day -2; Cyclophosphamide 50 mg/kg + MESNA.
Overall Number of Participants Analyzed	7
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

Adverse Events

Time Frame	Primary BMT studies have a critical toxicity period of 30 days after BMT day 0. During the critical toxicity period the most severe grade of all AE's is captured. Grade 1 and 2 AEs, hematological toxicities, and fevers are excluded. Serious Adverse Events/Unanticipated Problems are reported (excluding hematological toxicities and fevers) until 100 days after BMT day 0.
Adverse Event Reporting Description	All adverse events were collected using CTCAE 2.0 for the study. For reporting purpose, adverse event terms were converted using CTCAE v4.0.
Arm/Group Title	Allogeneic BMT/SCT Transplant
Arm/Group Description	Busulfan, Campath 1H, Cyclophosphamide and MESNA: Bone marrow infusion with pre-meds as per SOPs to take place on Day 0. Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest. Busulfan: Starting Day -9 / Busulfan 4.0 mg/kg/day IV divided into four doses daily for four days; total dose = 16 mg/kg. Campath 1H: Day -5 through Day -2; Campath-1H dosed as per institutional guidelines. Cyclophosphamide and MESNA: Day -5 through Day -2; Cyclophosphamide 50 mg/kg + MESNA.
All-Cause Mortality
	Allogeneic BMT/SCT Transplant
	Affected / at Risk (%)
Total	0/8 (0.00%)
Serious Adverse Events
	Allogeneic BMT/SCT Transplant
	Affected / at Risk (%)	# Events
Total	3/8 (37.50%)
Infections and infestations
Catheter-related infection † 1	1/8 (12.50%)	1
Metabolism and nutrition disorders
Hyponatremia † 1	1/8 (12.50%)	1
Nervous system disorders
Seizure † 1	1/8 (12.50%)	1
Skin and subcutaneous tissue disorders
Erythema multiforme † 1	1/8 (12.50%)	1
Vascular disorders
Hypertension † 1	1/8 (12.50%)	1
1 Term from vocabulary, CTCAE v4.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Allogeneic BMT/SCT Transplant
	Affected / at Risk (%)	# Events
Total	8/8 (100.00%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	1/8 (12.50%)	2
Cardiac disorders
Cardiac disorders - Other: Prolonged QTc interval (QTc > 0.48 seconds) † 1	1/8 (12.50%)	1
Cardiac disorders - Other: Supraventricular arrhythmias (SVT/atrial fibrillation/flutter) † 1	1/8 (12.50%)	1
Gastrointestinal disorders
Abdominal pain † 1	1/8 (12.50%)	1
Anal hemorrhage † 1	1/8 (12.50%)	2
Diarrhea † 1	1/8 (12.50%)	4
Mucositis oral † 1	1/8 (12.50%)	1
Nausea † 1	3/8 (37.50%)	3
Vomiting † 1	3/8 (37.50%)	6
Infections and infestations
Catheter-related infection † 1	1/8 (12.50%)	1
Infections and infestations - Other: BK viremia † 1	1/8 (12.50%)	1
Infections and infestations - Other: Candida Albicans in tongue culture † 1	1/8 (12.50%)	1
Infections and infestations - Other: Parainfluenza 3 respiratory infection † 1	1/8 (12.50%)	1
Investigations
Alanine aminotransferase increased † 1	1/8 (12.50%)	3
Aspartate aminotransferase increased † 1	6/8 (75.00%)	8
Blood bilirubin increased † 1	1/8 (12.50%)	6
GGT increased † 1	1/8 (12.50%)	2
Weight loss † 1	1/8 (12.50%)	1
Metabolism and nutrition disorders
Anorexia † 1	1/8 (12.50%)	1
Hyperglycemia † 1	1/8 (12.50%)	1
Hypocalcemia † 1	1/8 (12.50%)	1
Hyponatremia † 1	1/8 (12.50%)	1
Hypophosphatemia † 1	1/8 (12.50%)	1
Musculoskeletal and connective tissue disorders
Bone pain † 1	1/8 (12.50%)	1
Nervous system disorders
Headache † 1	2/8 (25.00%)	2
Seizure † 1	1/8 (12.50%)	2
Psychiatric disorders
Hallucinations † 1	2/8 (25.00%)	2
Respiratory, thoracic and mediastinal disorders
Hypoxia † 1	1/8 (12.50%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular † 1	1/8 (12.50%)	1
Vascular disorders
Hypertension † 1	2/8 (25.00%)	2
1 Term from vocabulary, CTCAE v4.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Tami D. John
• Organization: Baylor College of Medicine/Texas Children's Hospital
• Phone: 832-824-4723
• EMail: tdjohn@texaschildrens.org

• Responsible Party: Tami D. John, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT00578344
• Other Study ID Numbers: H-16447-SCALLOP; SCALLOP ( Other Identifier: Baylor College of Medicine )
• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Results First Submitted: April 3, 2020
• Results First Posted: July 31, 2020
• Last Update Posted: July 31, 2020