Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00153985
• Collaborator: Beth Israel Deaconess Medical Center (Other), Massachusetts General Hospital (Other), Brigham and Women's Hospital (Other), Emory University (Other), Feist-Weiller Cancer Center at Louisiana State University Health Sciences (Other), Ohio State University (Other)
• Enrollment: 2
• Locations: 6
• Duration (Months): 64
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if treatment with reduced-dose busulfex, fludarabine and alemtuzumab (CAMPATH) followed by sten cell infusion will allow for donor stem cells to grow in patients with hemoglobinopathies bone marrow and restore circulating blood counts. In addition the incidence and severity of side effects and of graft vs. host disease (GVHD) will be monitored.

Condition or Disease	Intervention/Treatment	Phase
Hemoglobinopathies; Sickle Cell Disease; Thalassemia	Drug: Busulfex; Drug: Fludarabine; Drug: Alemtuzumab; Procedure: Stem Cell Transfusion	Phase 2

Detailed Description

• In order to undergo transplant procedure, patients will be admitted to the hospital for approximately 10-14 days.

• To prepare patient's bone marrow to accept donor stem cells, they will receive fludarabine and busulfex. Fludarabine will be given intravenously once daily for 4 days. Busulfex will be given once daily for the same 4 days.

• One day before patients receive busulfex and fludarabine, they will also be given alemtuzumab intravenously once daily for 5 days.

• Three days after the end of chemotherapy, patients will receive the infusion of donor stem cells.

• If patients have thalassemia, they will receive subcutaneous injections of filgrastim starting on day one after the donor stem cell transfusion and will continue receiving filgrastim every day until it appears that the donor stem cells have been accepted. If the patient has sickle cell disease, filgrastim will not be given,

• Additional drugs will be given to help prevent infection (i.e. antibiotics).

• After stem cell infusion patients will be examined and have blood tests weekly for 1 month. Bone marrow biopsies, and blood work will also be performed 1 month, 3 months, 6 months and 1 year after stem cell infusion.

• Patients will be on the study for about 12 months. After study is completed progress will be monitored on an annual basis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multi-Center Study Using Allogeneic Stem Cell Transplantation Following Reduced Intensity Chemotherapy in Patients With Hemoglobinopathies
• Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Jul 1, 2009

Outcome Measures

Primary Outcome Measures

1. Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy. [3 years]

   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.

Secondary Outcome Measures

1. Solid Organ Toxicity Related to the Conditioning Regimen. [3 years]

   Outcome was measured by the assessment of organ toxicity related to Busulfex, fludarabine and alemtuzumab.

2. The Incidence of Grade II-IV Acute Graft vs. Host Disease. [3 years]

   Outcome was measured by incidence and severity of acute and chronic GVHD following donor stem cell infusion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with sickle cell disease should have one or more of the following: acute chest syndrome requiring hospitalization; nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours; recurrent caso-occlusive pain or recurrent priapism; sickle neuropathy; bilateral proliferative retinopathy and major visual impairment of at least one eye; osteonecrosis of multiple joints; transfusion dependence; vaso-occlusive.

• Patients with thalassemia should have one or more of the following: transfusion dependence; iron overload; presence of 2 or more alloantibodies against red cell antigens.

Exclusion Criteria:

• Pregnancy

• Acute hepatitis

• Cardiac ejection fraction < 30%

• Severe renal impairment

• Severe residual functional neurologic impairment

• Evidence of HIV infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Winship Cancer Institute-Emory University	Atlanta	Georgia	United States	30322
2	Feist-Weiller Cancer Center-LSU	Shreveport	Louisiana	United States	71130
3	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02115
6	Ohio State University College of Medicine	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• 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

Investigators

• Principal Investigator: Catherine J. Wu, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Catherine Wu, MD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00153985
• Other Study ID Numbers: 03-338
• First Posted: Sep 12, 2005
• Last Update Posted: Jul 30, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Catherine Wu, MD, Principal Investigator, Dana-Farber Cancer Institute: Hemoglobinopathies; Sickle cell anemia; sickle cell-hemoglobin C disease; sickle cell-B-thalassemia; transfusion-dependant thalassemia; allogeneic transplant; nonmyeloablative transplant; Stem cell transfusion; graft vs. host disease
• Additional relevant MeSH terms: Anemia, Sickle Cell; Thalassemia; Hemoglobinopathies; Fludarabine; Alemtuzumab; Busulfan

Study Results

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 Detail	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 Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25 (2)
Sex: Female, Male (Count of Participants)
Female	2 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%

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.
Measure Participants	2
Number [participants]	2 100%

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.
Measure Participants	2
Number [participants]	2 100%

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.
Measure Participants	2
Number [participants]	2 100%

Adverse Events

Time Frame	Through study completion in 2009 (or patient death)
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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Transplant for Severe Hemoglobinopathies
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Immune system disorders
Graft versus host disease	1/2 (50%)	1
Other (Not Including Serious) Adverse Events
	Transplant for Severe Hemoglobinopathies
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Infections and infestations
Infection	1/2 (50%)	1

Limitations/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.