Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT

Virginia Commonwealth University (VCU)

Status and phase: Completed; Phase 2

Conditions: Hodgkin Lymphoma; Multiple Myeloma; Non-Hodgkin's Lymphoma; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Myelodysplastic Syndrome; Leukemia; Acute Myeloid Leukemia

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00709592

NCI-2011-01698 (Other Identifier)

MCC-11561

Details and patient eligibility

About

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.

Full 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.

Enrollment: 42 patients

Sex: All

Ages: 40 to 70 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

ATG 1.7 mg/kg, TBI, transplant

Experimental group

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.

Treatment:

Drug: Tacrolimus

Procedure: Allogeneic PBSCT or BMT

Drug: Mycophenolate Mofetil

Biological: Thymoglobulin

Radiation: Total-Body Irradiation

ATG 2.5 mg/kg/d, TBI, transplant

Experimental group

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.

Treatment:

Drug: Tacrolimus

Procedure: Allogeneic PBSCT or BMT

Drug: Mycophenolate Mofetil

Biological: Thymoglobulin

Radiation: Total-Body Irradiation