Track topics on Twitter Track topics that are important to you
RATIONALE: Giving chemotherapy, such as busulfan and fludarabine phosphate, before a 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate, tacrolimus, and antithymocyte globulin before and after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with relapsed hematologic malignancies or secondary myelodysplasia previously treated with high-dose chemotherapy and autologous stem cell transplant .
- To demonstrate the efficacy of performing reduced-intensity conditioning allogeneic hematopoietic cell transplantation in patients with relapsed hematologic malignancies or secondary myelodysplasia after completion of prior high-dose chemotherapy and autologous hematopoietic stem cell transplantation.
- To compare the strategy of this regimen with the strategy used in CALGB-100002.
- To describe the response rate at 6 and 12 months in patients treated with this regimen.
- To describe the time-to-progression in patients treated with this regimen.
- To determine the ability to use pharmacokinetic-directed busulfan to achieve AUC within 20% of target AUC in > 80% of patients.
- To determine percent of donor chimerism in T-cell, myeloid and B-cell populations achieved with this regimen compared with CALGB-100002.
- To determine the risk of acute and chronic graft-versus-host disease and other toxicities of this regimen in these patients.
- To describe the overall survival and disease-free survival of patients treated on this regimen.
- To determine the rate of viral, bacterial, and fungal opportunistic infections occurring in the first year after transplantation compared with CALGB-100002.
OUTLINE: This is a multicenter study.
- Preparative Regimen:
- Busulfan test dose: Patients receive busulfan IV over 45 minutes once during days -14 and -9.
- Busulfan treatment dose: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV over 3 hours on days -6 to -3.
- Graft-vs-Host Disease (GVHD) Prophylaxis:
- HLA-identical donor: Patients receive antithymocyte globulin IV over 6-10 hours on days -6 to -5; oral tacrolimus twice daily on days -2 to 90 followed by a taper* as tolerated until day 150 or 180; and methotrexate IV on days 1, 3, and 6.
NOTE: * Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is < 50% at day 60 or patient has progressive disease.
- Matched-unrelated donor: Patients receive antithymocyte globulin, tacrolimus, and methotrexate as in HLA-identical donor regimen. Patients also receive oral mycophenolate mofetil twice daily on days 0 to 60.
- Allogeneic Stem Cell Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim subcutaneously daily beginning on day 7 and continuing until blood counts recover.
- Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.
Blood samples are collected at baseline and then periodically during study therapy for pharmacokinetic studies.
After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for up to 5½ years.
Masking: Open Label, Primary Purpose: Treatment
anti-thymocyte globulin, donor lymphocytes, filgrastim, therapeutic allogeneic lymphocytes, busulfan, fludarabine phosphate, methotrexate, mycophenolate mofetil, tacrolimus, pharmacological study, reduced-intensity transplant conditioning procedure, allog
Not yet recruiting
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-08-27T03:13:54-0400
RATIONALE: Giving chemotherapy before a donor peripheral blood stem cell transplant helps stop both the growth of cancer cells and the patient's immune system from rejecting the donor's st...
RATIONALE: Giving chemotherapy, such as fludarabine and melphalan, before a donor peripheral blood stem cell transplant helps stop the growth of tumor cells. It also stops the patient's im...
This study was designed to test the safety and efficacy of up to 3 pancreatic alloislet transplants in type 1 diabetic patients with hypoglycemia unawareness. 6 subjects were transplanted...
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It...
RATIONALE: Biological therapies, such as anti-thymocyte globulin, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as ...
Impact of antithymocyte globulin doses in reduced intensity conditioning before allogeneic transplantation from matched sibling donor for patients with acute myeloid leukemia: a report from the acute leukemia working party of European group of Bone Marrow Transplantation.
Antithymocyte globulin (ATG) is commonly used for graft-vs.-host disease (GVHD) prophylaxis in unrelated donor allogeneic transplantation (Allo-HSCT). However, its use is still controversial in matche...
Relapse of cancer remains one of the primary causes of treatment failure and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). A multitude of approaches have been used in the ...
Pure red cell aplasia (PRCS) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many therapeutic options are available to treat this condition, includin...
Utilization of unrelated donors and cord blood units (CBUs) for allogeneic hematopoietic cell transplantation continues to increase. Understanding the practices of donor selection by transplant center...
Immune evasion by tumors includes several different mechanisms, including the inefficiency of antigen presenting cells (APCs) to trigger anti-tumor T cell responses. B lymphocytes may display a pro-tu...
The transfer of lymphocytes from a donor to a recipient or reinfusion to the donor.
Immunizing agent containing IMMUNOGLOBULIN G anti-Rho(D) used for preventing Rh immunization in Rh-negative individuals exposed to Rh-positive red blood cells.
Protection from an infectious disease agent that is mediated by B- and T- LYMPHOCYTES following exposure to specific antigen, and characterized by IMMUNOLOGIC MEMORY. It can result from either previous infection with that agent or vaccination (IMMUNITY, ACTIVE), or transfer of antibody or lymphocytes from an immune donor (IMMUNIZATION, PASSIVE).
A glycoprotein migrating as alpha 1-globulin, molecular weight 70,000 to 120,000. The protein, which is present in increased amounts in the plasma during pregnancy, binds mainly progesterone, with other steroids including testosterone competing weakly.
Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use.
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...