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Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00709592
First Posted: July 3, 2008
Last Update Posted: September 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Virginia Commonwealth University
  Purpose
One of two different doses of thymoglobulin will allow bone marrow engraftment with minimal Graft-versus-Host Disease and allow adequate immune response to allow the transplanted stem cells to replace the tumor cells.

Condition Intervention Phase
Non-Hodgkin's Lymphoma Leukemia Multiple Myeloma Acute Myeloid Leukemia Hodgkin Lymphoma Chronic Lymphocytic Leukemia Chronic Myelogenous Leukemia Myelodysplastic Syndrome Biological: Thymoglobulin Radiation: Total-Body Irradiation Procedure: Allogeneic PBSCT or BMT Drug: Tacrolimus Drug: Mycophenolate Mofetil Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduced Intensity Myeloablative Total Body Irradiation and Thymoglobulin Followed by Allogeneic Peripheral Blood Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • The Comparison of Functional Immune Reconstitution at 6-9 Months Following Transplant as Measured by Antibody Response to Vaccination With Inactivated Hepatitis A or B Vaccine. [ Time Frame: Up to 9 months following transplant ]
    A positive test result will indicate immune reconstitution, while a negative test results will indicate lack of immune reconstitution. Participants not done (ND) will be counted with the negative (Neg).


Secondary Outcome Measures:
  • Engraftment of Donor Hematopoietic Stem Cells, as Measured by Neutrophil and Platelet Counts [ Time Frame: 12 day median ]
  • Survival [ Time Frame: 2-year survival rate (%) ]
  • Treatment Related Mortality [ Time Frame: Day 100 ]
  • Event-free Survival [ Time Frame: 2 years ]
  • Relapse [ Time Frame: 2 year relapse rate (%) ]
    Patients with different disease relapses was determined according to current clinical standards based on the disease. For example, AML or MDS relapse is determined by a bone marrow biopsy. Multiple myeloma relapse requires a number of labs and/or biopsy to diagnose such as SPEP, UPEP, immunofixation, serum and urine light chains. In lymphoma disease is followed using CT and/or PET scans.

  • Donor Lymphocyte Infusion [ Time Frame: 2 year rate of DLI ]
  • Acute Graft-Versus-Host Disease (GVHD) [ Time Frame: 2 year rate (%) ]
  • Chronic Graft-Versus-Host Disease (GVHD) [ Time Frame: 2 year GVHD rate ]

Enrollment: 42
Actual Study Start Date: July 21, 2008
Study Completion Date: June 28, 2017
Primary Completion Date: February 15, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATG 1.7 mg/kg, TBI, transplant
(Rabbit-ATG;Thymoglobulin,Genzyme) ATG 5.1 mg/kg in three divided doses (1.7 mg/kg/d) given over three days (day -9 to -7) followed by 450 cGy TBI and tacrolimus plus MMF GVHD prophylaxis. Patients receive lower dose anti-thymocyte globulin IV on days -9 to -7. Patients undergo total-body radiation (TBI) twice daily (BID) on day -1 and once daily (QD) on day 0. Patients then undergo peripheral blood stem cells or bone marrow transplant on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: patients receive tacrolimus orally (PO) on days -2 to 90-120 with taper for 2 months, and mycophenolate mofetil (MMF) PO BID on days 0-30.
Biological: Thymoglobulin
Patients eligible for participation in this study will be randomized between receiving rabbit ATG for 3 days. Thymoglobulin will be administered according to VCU BMT standard of care starting day -9 and continued daily through day -7.
Other Names:
  • anti-thymocyte globulin (rabbit)
  • ATG
  • Genzyme
  • anti-thymocyte globulin
  • Rabbit
  • Rabbit-ATG
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Whole-Body Irradiation
  • Total Body Irradiation [TBI]
Procedure: Allogeneic PBSCT or BMT
Undergo allogeneic PBSCT or BMT
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Blood Stem Cell Transplantation [Allogenic PBSCT]
  • Allogeneic Bone Marrow Transplantation [BMT]
  • Allogeneic BMT
  • Allogeneic Hematopoietic Stem Cell Transplantation
  • HSCT
Drug: Tacrolimus
Given PO
Other Names:
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic
Drug: Mycophenolate Mofetil
Given PO
Other Names:
  • CellCept
  • MMF
Experimental: ATG 2.5 mg/kg/d, TBI, transplant
(Rabbit-ATG;Thymoglobulin,Genzyme) ATG 7.5 mg/kg in three divided doses (2.5 mg/kg/d) given over three days (day -9 to -7) followed by 450 cGy TBI and tacrolimus plus MMF GVHD prophylaxis. Patients receive higher dose anti-thymocyte globulin intravenously (IV) on days -9 to -7. Patients undergo total-body radiation (TBI) twice daily (BID) on day -1 and once daily (QD) on day 0. Patients then undergo peripheral blood stem cells or bone marrow transplant on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: patients receive tacrolimus orally (PO) on days -2 to 90-120 with taper for 2 months, and mycophenolate mofetil (MMF) PO BID on days 0-30.
Biological: Thymoglobulin
Patients eligible for participation in this study will be randomized between receiving rabbit ATG for 3 days. Thymoglobulin will be administered according to VCU BMT standard of care starting day -9 and continued daily through day -7.
Other Names:
  • anti-thymocyte globulin (rabbit)
  • ATG
  • Genzyme
  • anti-thymocyte globulin
  • Rabbit
  • Rabbit-ATG
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Whole-Body Irradiation
  • Total Body Irradiation [TBI]
Procedure: Allogeneic PBSCT or BMT
Undergo allogeneic PBSCT or BMT
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Blood Stem Cell Transplantation [Allogenic PBSCT]
  • Allogeneic Bone Marrow Transplantation [BMT]
  • Allogeneic BMT
  • Allogeneic Hematopoietic Stem Cell Transplantation
  • HSCT
Drug: Tacrolimus
Given PO
Other Names:
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic
Drug: Mycophenolate Mofetil
Given PO
Other Names:
  • CellCept
  • MMF

Detailed Description:
This randomized phase II trial studies how well giving low dose total-body irradiation (TBI) with anti-thymocyte globulin followed by donor peripheral blood stem cell transplant (PBSCT) works in treating patients with hematologic malignancies. Giving reduced intensity total-body irradiation and anti-thymocyte globulin before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with antithymocyte globulin before transplant may stop this from happening.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with hematological malignancies for which allogeneic stem cell transplantation indicated including non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute myeloid leukemia (AML), Hodgkin lymphoma (HD), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS)
  • Patients with HLA compatible related or unrelated stem cell donor, willing and able to serve as an allogenic HSC donor. Unrelated donors have to be matched at HLA-A, B, C and DRB1 loci. A single locus mismatch will be tolerated in the event a more closely matched donor is not available.
  • Patients age >/=40 to </=70 with an ECOG performance status < 2
  • Patients between 18 and 40 years of age will be eligible only if they have co-morbidities precluding conventional allogeneic transplantation with full intensity myeloablative conditioning
  • Adequate cardiac, pulmonary, renal and hepatic function for transplant
  • Negative serology for HIV
  • Negative serum pregnancy test
  • Patients who have received therapeutic radiation to a localized field will be eligible, provided critical structure tolerance doses have not been exceeded
  • Patients who have had prior myeloablative autologous transplant will be eligible

Exclusion Criteria:

  • Evidence of uncontrolled viral, fungal, bacterial infection
  • Evidence of active meningeal or CNS disease
  • Prior therapy with rabbit ATG, prior treatment with equine ATG is allowed if more than 3 months ago
  • Breast feeding mothers are excluded
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00709592


Locations
United States, Virginia
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Sponsors and Collaborators
Virginia Commonwealth University
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Amir Toor, MD Massey Cancer Center
  More Information

Additional Information:
Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00709592     History of Changes
Other Study ID Numbers: MCC-11561
NCI-2011-01698 ( Other Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: July 1, 2008
First Posted: July 3, 2008
Results First Submitted: February 1, 2015
Results First Posted: February 12, 2015
Last Update Posted: September 18, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Virginia Commonwealth University:
total body irradiation
Allogeneic Peripheral Blood Stem Cell Transplantation
thymoglobulin

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Myeloid, Acute
Multiple Myeloma
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myeloid
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Leukemia, B-Cell
Myeloproliferative Disorders