Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT

NCT00709592 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MCC-11561NCI-2011-01698
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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).

  Up to 9 months following transplant

Secondary Outcomes (8)

• Engraftment of Donor Hematopoietic Stem Cells, as Measured by Time in Days to Neutrophil and Platelet Count Recovery Following Allogeneic PBSCT.

  Up to 52 weeks post transplant.

• Survival

  2-year survival rate (%)

• Treatment Related Mortality

  Day 100

• Event-free Survival

  2 years

• Relapse

  2 year relapse rate (%)

Study Arms (2)

ATG 1.7 mg/kg, TBI, transplant

EXPERIMENTAL

(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; Radiation: Total-Body Irradiation; Procedure: Allogeneic PBSCT or BMT; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

ATG 2.5 mg/kg/d, TBI, transplant

EXPERIMENTAL

(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; Radiation: Total-Body Irradiation; Procedure: Allogeneic PBSCT or BMT; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

Interventions

Thymoglobulin BIOLOGICAL

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.

Also known as: anti-thymocyte globulin (rabbit), ATG, Genzyme, anti-thymocyte globulin, Rabbit, Rabbit-ATG

ATG 1.7 mg/kg, TBI, transplant; ATG 2.5 mg/kg/d, TBI, transplant

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: Whole-Body Irradiation, Total Body Irradiation [TBI]

ATG 1.7 mg/kg, TBI, transplant; ATG 2.5 mg/kg/d, TBI, transplant

Allogeneic PBSCT or BMT PROCEDURE

Undergo allogeneic PBSCT or BMT

Also known as: 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

ATG 1.7 mg/kg, TBI, transplant; ATG 2.5 mg/kg/d, TBI, transplant

Tacrolimus DRUG

Given PO

Also known as: Fujimycin, Hecoria, Prograf, Protopic

ATG 1.7 mg/kg, TBI, transplant; ATG 2.5 mg/kg/d, TBI, transplant

Mycophenolate Mofetil DRUG

Given PO

Also known as: CellCept, MMF

ATG 1.7 mg/kg, TBI, transplant; ATG 2.5 mg/kg/d, TBI, transplant

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Related Links

• VCU Massey Cancer Center

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia; Multiple Myeloma; Leukemia, Myeloid, Acute; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes

Interventions

thymoglobulin; Antilymphocyte Serum; Whole-Body Irradiation; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Myeloid; Leukemia, B-Cell; Leukemia, Lymphoid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Radiotherapy; Therapeutics; Investigative Techniques; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Amir A Toor, MD
• Organization: Virginia Commonwealth University

atoor@mcvh-vcu.edu

804-828-4360

Study Officials

• Amir Toor, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2008
• First Posted: July 3, 2008
• Study Start: July 21, 2008
• Primary Completion: February 15, 2014
• Study Completion: June 28, 2017
• Last Updated: November 9, 2018
• Results First Posted: February 12, 2015

Record last verified: 2018-11

Locations

US (1)