Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies

• ClinicalTrials.gov Identifier: NCT00153985
• Recruitment Status: Completed
• First Posted: September 12, 2005
• Results First Posted: March 12, 2013
• Last Update Posted: July 30, 2013
• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Beth Israel Deaconess Medical Center; Massachusetts General Hospital; Brigham and Women's Hospital; Emory University; Feist-Weiller Cancer Center at Louisiana State University Health Sciences; Ohio State University
• Information provided by (Responsible Party): Catherine Wu, MD, Dana-Farber Cancer Institute

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Hemoglobinopathies; Sickle Cell Disease; Thalassemia
• Interventions: Drug: Busulfex; Drug: Fludarabine; Drug: Alemtuzumab; Procedure: Stem Cell Transfusion
• Enrollment: 2

Participant Flow

Recruitment Details	Activated for enrollment 3/4/2004. Closed to enrollment 4/25/2008. Participating institutions included: Dana-Farber Cancer Institute, Boston, Massachusetts, Feist-Weiller Cancer Center, LSU Health Sciences Center, Shreveport, Louisiana and Winship Cancer Institute, Emory University, Atlanta, Georgia
Pre-assignment Details	All enrolled patients received a stem cell transplant.

Arm/Group Title	Transplant for Severe Hemoglobinopathies
Arm/Group Description	Patients with severe hemoglobinopathies (eg. sickle cell disease, thalassemia major) with related donors who are identical at 6 HLA loci: (HLA-A, HLA-B, HLA-DRB1). The preparative regimen consisted of Busulfex, fludarabine and alemtuzumab.
Period Title: Overall Study
Started	2
Completed	2
Not Completed	0

Baseline Characteristics

Arm/Group Title		Transplant for Severe Hemoglobinopathies
Arm/Group Description		Patients with severe hemoglobinopathies (eg. sickle cell disease, thalassemia major) with related donors who are identical at 6 HLA loci: (HLA-A, HLA-B, HLA-DRB1). The preparative regimen consisted of Busulfex, fludarabine and alemtuzumab.
Overall Number of Baseline Participants		2
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	2 100.0%
	>=65 years	0 0.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	2 participants
		25 (2)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2 participants
	Female	2 100.0%
	Male	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	2 participants
		2

Outcome Measures

1. Primary Outcome

Title	Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy.
Description	Outcome was measured by ANC >500 for three consecutive days prior to day 30 after PBSC infusion, >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods prior to day 45 after PBSC infusion and >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods after day 180 after PBSC infusion.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

All patients enrolled.

Arm/Group Title	Transplant for Severe Hemoglobinopathies
Arm/Group Description:	Patients with severe hemoglobinopathies (eg. sickle cell disease, thalassemia major) with related donors who are identical at 6 HLA loci: (HLA-A, HLA-B, HLA-DRB1). The preparative regimen consisted of Busulfex, fludarabine and alemtuzumab.
Overall Number of Participants Analyzed	2
Measure Type: Number; Unit of Measure: participants
	2

2. Secondary Outcome

Title	Solid Organ Toxicity Related to the Conditioning Regimen.
Description	Outcome was measured by the assessment of organ toxicity related to Busulfex, fludarabine and alemtuzumab.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

All patients enrolled.

Arm/Group Title	Transplant for Severe Hemoglobinopathies
Arm/Group Description:	Patients with severe hemoglobinopathies (eg. sickle cell disease, thalassemia major) with related donors who are identical at 6 HLA loci: (HLA-A, HLA-B, HLA-DRB1). The preparative regimen consisted of Busulfex, fludarabine and alemtuzumab.
Overall Number of Participants Analyzed	2
Measure Type: Number; Unit of Measure: participants
	2

3. Secondary Outcome

Title	The Incidence of Grade II-IV Acute Graft vs. Host Disease.
Description	Outcome was measured by incidence and severity of acute and chronic GVHD following donor stem cell infusion.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

All patients enrolled.

Arm/Group Title	Transplant for Severe Hemoglobinopathies
Arm/Group Description:	Patients with severe hemoglobinopathies (eg. sickle cell disease, thalassemia major) with related donors who are identical at 6 HLA loci: (HLA-A, HLA-B, HLA-DRB1). The preparative regimen consisted of Busulfex, fludarabine and alemtuzumab.
Overall Number of Participants Analyzed	2
Measure Type: Number; Unit of Measure: participants
	2

Adverse Events

Time Frame	Through study completion in 2009 (or patient death)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Transplant for Severe Hemoglobinopathies
Arm/Group Description	Patients with severe hemoglobinopathies (eg. sickle cell disease, thalassemia major) with related donors who are identical at 6 HLA loci: (HLA-A, HLA-B, HLA-DRB1). The preparative regimen consisted of Busulfex, fludarabine and alemtuzumab.
All-Cause Mortality
	Transplant for Severe Hemoglobinopathies
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Transplant for Severe Hemoglobinopathies
	Affected / at Risk (%)	# Events
Total	1/2 (50.00%)
Immune system disorders
Graft versus host disease †	1/2 (50.00%)	1
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Transplant for Severe Hemoglobinopathies
	Affected / at Risk (%)	# Events
Total	1/2 (50.00%)
Infections and infestations
Infection †	1/2 (50.00%)	1
† Indicates events were collected by systematic assessment

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

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.

Results Point of Contact

• Name/Title: Catherine Wu, MD
• Organization: Dana-Farber Cancer Institute
• Phone: 617-632-5943
• EMail: cwu@partners.org

Publications of Results:

Armistead PM, Mohseni M, Gerwin R, Walsh EC, Iravani M, Chahardouli B, Rostami S, Zhang W, Neuberg D, Rioux J, Ghavamzadeh A, Ritz J, Antin JH, Wu CJ. Erythroid-lineage-specific engraftment in patients with severe hemoglobinopathy following allogeneic hematopoietic stem cell transplantation. Exp Hematol. 2008 Sep;36(9):1205-15. doi: 10.1016/j.exphem.2008.04.004. Epub 2008 Jun 11.

• Responsible Party: Catherine Wu, MD, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00153985
• Other Study ID Numbers: 03-338
• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Results First Submitted: December 5, 2012
• Results First Posted: March 12, 2013
• Last Update Posted: July 30, 2013