Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Malignancies or Secondary Myelodysplasia Previously Treated With High-Dose Chemotherapy and Autologous Stem Cell Transplant
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 .
Multiple Myeloma and Plasma Cell Neoplasm
Biological: anti-thymocyte globulin
Biological: donor lymphocytes
Biological: therapeutic allogeneic lymphocytes
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Other: pharmacological study
Other: reduced-intensity transplant conditioning procedure
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation as Second Transplantation for Patients With Disease Relapse or Myelodysplasia After Prior Autologous Transplantation|
- Event-free survival (EFS) [ Designated as safety issue: No ]
- Comparison of EFS distribution to that of CALGB-100002 [ Designated as safety issue: No ]
- Complete response rate [ Designated as safety issue: No ]
- Complete (> 90%) or mixed donor chimerism [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Rate of opportunistic infections [ Designated as safety issue: No ]
- Graft-versus-host disease at 6 months [ Designated as safety issue: No ]
|Study Start Date:||December 2010|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01118013
|United States, Delaware|
|Tunnell Cancer Center at Beebe Medical Center|
|Lewes, Delaware, United States, 19958|
|CCOP - Christiana Care Health Services|
|Newark, Delaware, United States, 19713|
|United States, Florida|
|Florida Hospital Cancer Institute at Florida Hospital Orlando|
|Orlando, Florida, United States, 32803-1273|
|United States, Maryland|
|Greenebaum Cancer Center at University of Maryland Medical Center|
|Baltimore, Maryland, United States, 21201|
|Union Hospital of Cecil County|
|Elkton MD, Maryland, United States, 21921|
|United States, Missouri|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis|
|Saint Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Cancer Institute of New Jersey at Cooper - Voorhees|
|Voorhees, New Jersey, United States, 08043|
|United States, New York|
|New York Weill Cornell Cancer Center at Cornell University|
|New York, New York, United States, 10021|
|United States, North Carolina|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|United States, Ohio|
|Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210-1240|
|Principal Investigator:||Asad Bashey, MD, PhD||Blood and Marrow Transplant Group of Georgia|