search
Back to results

Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT

Primary Purpose

Non-Hodgkin's Lymphoma, Leukemia, Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Thymoglobulin
Total-Body Irradiation
Allogeneic PBSCT or BMT
Tacrolimus
Mycophenolate Mofetil
Sponsored by
Virginia Commonwealth University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma focused on measuring total body irradiation, Allogeneic Peripheral Blood Stem Cell Transplantation, thymoglobulin

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Virginia Commonwealth University/Massey Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

ATG 1.7 mg/kg, TBI, transplant

ATG 2.5 mg/kg/d, TBI, transplant

Arm Description

(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.

(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.

Outcomes

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.
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 Time in Days to Neutrophil and Platelet Count Recovery Following Allogeneic PBSCT.
Survival
Treatment Related Mortality
Event-free Survival
Relapse
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
Acute Graft-Versus-Host Disease (GVHD)
Chronic Graft-Versus-Host Disease (GVHD)

Full Information

First Posted
July 1, 2008
Last Updated
November 7, 2018
Sponsor
Virginia Commonwealth University
Collaborators
Genzyme, a Sanofi Company
search

1. Study Identification

Unique Protocol Identification Number
NCT00709592
Brief Title
Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT
Official Title
Reduced Intensity Myeloablative Total Body Irradiation and Thymoglobulin Followed by Allogeneic Peripheral Blood Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
July 21, 2008 (Actual)
Primary Completion Date
February 15, 2014 (Actual)
Study Completion Date
June 28, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
Collaborators
Genzyme, a Sanofi Company

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, Leukemia, Multiple Myeloma, Acute Myeloid Leukemia, Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Myelodysplastic Syndrome
Keywords
total body irradiation, Allogeneic Peripheral Blood Stem Cell Transplantation, thymoglobulin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ATG 1.7 mg/kg, TBI, transplant
Arm Type
Experimental
Arm Description
(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.
Arm Title
ATG 2.5 mg/kg/d, TBI, transplant
Arm Type
Experimental
Arm Description
(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.
Intervention Type
Biological
Intervention Name(s)
Thymoglobulin
Other Intervention Name(s)
anti-thymocyte globulin (rabbit), ATG, Genzyme, anti-thymocyte globulin, Rabbit, Rabbit-ATG
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Total-Body Irradiation
Other Intervention Name(s)
Whole-Body Irradiation, Total Body Irradiation [TBI]
Intervention Description
Undergo TBI
Intervention Type
Procedure
Intervention Name(s)
Allogeneic PBSCT or BMT
Other Intervention Name(s)
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
Intervention Description
Undergo allogeneic PBSCT or BMT
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Fujimycin, Hecoria, Prograf, Protopic
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
CellCept, MMF
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
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.
Description
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).
Time Frame
Up to 9 months following transplant
Secondary Outcome Measure Information:
Title
Engraftment of Donor Hematopoietic Stem Cells, as Measured by Time in Days to Neutrophil and Platelet Count Recovery Following Allogeneic PBSCT.
Time Frame
Up to 52 weeks post transplant.
Title
Survival
Time Frame
2-year survival rate (%)
Title
Treatment Related Mortality
Time Frame
Day 100
Title
Event-free Survival
Time Frame
2 years
Title
Relapse
Description
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.
Time Frame
2 year relapse rate (%)
Title
Donor Lymphocyte Infusion
Time Frame
2 year rate of DLI
Title
Acute Graft-Versus-Host Disease (GVHD)
Time Frame
2 year rate (%)
Title
Chronic Graft-Versus-Host Disease (GVHD)
Time Frame
2 year GVHD rate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amir Toor, MD
Organizational Affiliation
Massey Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0037
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.massey.vcu.edu/
Description
VCU Massey Cancer Center

Learn more about this trial

Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT

We'll reach out to this number within 24 hrs