Intensity-Modulated Radiation Therapy, Fludarabine, and Melphalan Followed by a Donor Stem Cell Transplant in Treating Patients With Hematological Cancer

• Toxicity of helical tomotherapy (HT) in combination with fludarabine and melphalan followed by allogeneic stem cell transplantation [ Time Frame: 100 days post treatment ] [ Designated as safety issue: Yes ]
  
• Safety [ Time Frame: 100 days post treatment ] [ Designated as safety issue: Yes ]
  

• Incidence of neutrophil and platelet engraftment [ Time Frame: 100 days post treatment ] [ Designated as safety issue: No ]
  
• Incidence of relapse [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
  
• Incidence of acute and chronic transplant-related complications, including acute and chronic graft-vs-host disease [ Time Frame: 1 year post treatment ] [ Designated as safety issue: No ]
  
• Secondary malignancy, including treatment-related myelodysplastic syndrome [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
  
• Overall survival on day 180 days post-transplant [ Time Frame: 180 days post-transplant ] [ Designated as safety issue: No ]
  
• Disease-free survival 180 days post-transplant [ Time Frame: 180 days post-transplant ] [ Designated as safety issue: No ]
  

Drug: fludarabine phosphate
25 mg/m2 day -7 through day -3 prior to transplant
Drug: melphalan
140 mg/m2 day -2 prior to transplant
Procedure: allogeneic hematopoietic stem cell transplantation
Cells infused on Day 0 of transplant regimen
Radiation: intensity-modulated radiation therapy
Each fraction is 150 cGy, 2 fractions each day on day -7 through day -4 prior to transplant

OBJECTIVES:

Primary

• To assess the feasibility, in terms of toxicity and safety, of helical tomotherapy (HT) in combination with fludarabine and melphalan as a preparative regimen for allogeneic stem cell transplantation in patients with hematological malignancies.

Secondary

• To evaluate, within the confines of this pilot study, the incidence of neutrophil and platelet engraftment, survival on day +180, overall survival, and disease-free survival in patients with hematological malignancies.
• To evaluate the incidence of primary and secondary engraftment failure, incidence of relapse, incidence of acute and chronic transplant-related complications including veno-occlusion disease of the liver (VOD), organ toxicity, secondary malignancy including treatment-related myelodysplastic syndrome, and acute and chronic graft-versus-host disease(GVHD), as well as post-transplant chimerism.

OUTLINE: Patients undergo intensity-modulated radiotherapy using helical tomotherapy to the bone marrow compartments, major lymph node regions (mediastinal, para-aortic, and pelvic), and spleen twice daily on days -7 to -4 (or days -9 to -6 for patients receiving tacrolimus and sirolimus for graft-vs-host disease [GVHD] prophylaxis). Patients also receive fludarabine IV on days -7 to -3 (or days -9 to -5), and melphalan IV over 2-20 minutes on day -2 (or day -4). Patients then undergo allogeneic hematopoietic stem cell transplantation on day 0.

After completion of study treatment, patients are followed at day 100, 6 months, 1 year, and 2 years.