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

Tracking Information

• First Submitted Date: September 8, 2005
• First Posted Date: September 12, 2005
• Results First Submitted Date: December 5, 2012
• Results First Posted Date: March 12, 2013
• Last Update Posted Date: July 30, 2013
• Study Start Date: March 2004
• Actual Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 6, 2013)

Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy. [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: September 8, 2005): To determine if the preparative regimen of busulfex, fludarabine and alemtuzumab (CAMPATH) will generate stable engraftment with donor stem cells in patients with severe hemoglobinopathy.

Current Secondary Outcome Measures (submitted: February 6, 2013)

• Solid Organ Toxicity Related to the Conditioning Regimen. [ Time Frame: 3 years ]
  Outcome was measured by the assessment of organ toxicity related to Busulfex, fludarabine and alemtuzumab.
• The Incidence of Grade II-IV Acute Graft vs. Host Disease. [ Time Frame: 3 years ]
  Outcome was measured by incidence and severity of acute and chronic GVHD following donor stem cell infusion.

Original Secondary Outcome Measures (submitted: September 8, 2005)

• To assess the safety of busulfex, fludarabine and alemtuzumab
• to describe the incidence and severity of acute or chronic graft vs. host disease.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies
• Official Title: Multi-Center Study Using Allogeneic Stem Cell Transplantation Following Reduced Intensity Chemotherapy in Patients With Hemoglobinopathies
• 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.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hemoglobinopathies
• Sickle Cell Disease
• Thalassemia

Intervention

• Drug: Busulfex
  Given once daily for 4 days
• Drug: Fludarabine
  Given intravenously once daily for 4 days
• Drug: Alemtuzumab
  One day before fludarabine and busulfex are started, alemtuzumab will be given once daily for 5 days.
  Other Name: CAMPATH
• Procedure: Stem Cell Transfusion
  Performed three days after the end of chemotherapy

• Study Arms: Not Provided
• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 6, 2013): 2
• Original Enrollment (submitted: September 8, 2005): 20
• Actual Study Completion Date: July 2009
• Actual Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00153985
• Other Study ID Numbers: 03-338
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Catherine Wu, MD, Dana-Farber Cancer Institute
• Original Responsible Party: Not Provided
• Current Study Sponsor: Dana-Farber Cancer Institute
• Original Study Sponsor: Same as current

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

Investigators

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

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: July 2013