Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT

November 7, 2018 updated by: Virginia Commonwealth University

Reduced Intensity Myeloablative Total Body Irradiation and Thymoglobulin Followed by Allogeneic Peripheral Blood Stem Cell Transplantation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Richmond, Virginia, United States, 23298-0037
        • Virginia Commonwealth University/Massey Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Mycophenolate Mofetil
Given PO
Other Names:
  • CellCept
  • MMF
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Whole-Body Irradiation
  • Total Body Irradiation [TBI]
Drug: Tacrolimus
Given PO
Other Names:
  • Prograf
  • Hecoria
  • Fujimycin
  • Protopic
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:
  • ATG
  • Genzyme
  • anti-thymocyte globulin
  • anti-thymocyte globulin (rabbit)
  • Rabbit
  • Rabbit-ATG
Procedure: Allogeneic PBSCT or BMT
Undergo allogeneic PBSCT or BMT
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • HSCT
  • Allogeneic BMT
  • Allogeneic Hematopoietic Stem Cell Transplantation
  • Peripheral Blood Stem Cell Transplantation [Allogenic PBSCT]
  • Allogeneic Bone Marrow Transplantation [BMT]
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.
Drug: Mycophenolate Mofetil
Given PO
Other Names:
  • CellCept
  • MMF
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Whole-Body Irradiation
  • Total Body Irradiation [TBI]
Drug: Tacrolimus
Given PO
Other Names:
  • Prograf
  • Hecoria
  • Fujimycin
  • Protopic
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:
  • ATG
  • Genzyme
  • anti-thymocyte globulin
  • anti-thymocyte globulin (rabbit)
  • Rabbit
  • Rabbit-ATG
Procedure: Allogeneic PBSCT or BMT
Undergo allogeneic PBSCT or BMT
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • HSCT
  • Allogeneic BMT
  • Allogeneic Hematopoietic Stem Cell Transplantation
  • Peripheral Blood Stem Cell Transplantation [Allogenic PBSCT]
  • Allogeneic Bone Marrow Transplantation [BMT]

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Up to 9 months following transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival
Time Frame: 2 years
2 years
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.
Up to 52 weeks post transplant.
Survival
Time Frame: 2-year survival rate (%)
2-year survival rate (%)
Treatment Related Mortality
Time Frame: Day 100
Day 100
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.
2 year relapse rate (%)
Donor Lymphocyte Infusion
Time Frame: 2 year rate of DLI
2 year rate of DLI
Acute Graft-Versus-Host Disease (GVHD)
Time Frame: 2 year rate (%)
2 year rate (%)
Chronic Graft-Versus-Host Disease (GVHD)
Time Frame: 2 year GVHD rate
2 year GVHD rate

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Virginia Commonwealth University

Collaborators

Genzyme, a Sanofi Company

Investigators

  • Principal Investigator: Amir Toor, MD, Massey Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 21, 2008

Primary Completion (Actual)

February 15, 2014

Study Completion (Actual)

June 28, 2017

Study Registration Dates

First Submitted

July 1, 2008

First Submitted That Met QC Criteria

July 2, 2008

First Posted (Estimate)

July 3, 2008

Study Record Updates

Last Update Posted (Actual)

November 9, 2018

Last Update Submitted That Met QC Criteria

November 7, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-11561
  • NCI-2011-01698 (Other Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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