Total Marrow and Total Lymph Node Irradiation, Fludarabine, and Melphalan Followed By Donor Stem Cell Transplant in Treating Patients With Advanced Hematological Cancer That Has Not Responded to Treatment
RATIONALE: Giving total marrow and total lymph node irradiation together with low doses of chemotherapy before a donor 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. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).
PURPOSE: This phase I trial is studying the side effects and best dose of total marrow and total lymph node irradiation when given together with fludarabine and melphalan followed by donor stem cell transplant in treating patients with advanced hematological cancer that has not responded to treatment.
Chronic Myeloproliferative Disorders
Multiple Myeloma and Plasma Cell Neoplasm
Drug: fludarabine phosphate
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Radiation: intensity-modulated radiation therapy
Radiation: total marrow irradiation
Radiation: total nodal irradiation
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Phase I Study of Escalating Doses of Radiation Therapy Using Helical Tomotherapy in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With Advanced and Hematological Malignancies Who Are Not Eligible for Fully Myeloablative Regimen|
- Maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation using helical tomotherapy [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Frequency of clinical response [ Designated as safety issue: No ]
- Frequency of primary and secondary engraftment failure [ Designated as safety issue: No ]
- Time to neutrophil and platelet engraftment [ Designated as safety issue: No ]
- Incidence of acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: No ]
|Study Start Date:||November 2008|
|Study Completion Date:||October 2010|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
- To determine the maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation (TMLI) using helical tomotherapy in combination with a reduced-intensity preparative regimen comprising fludarabine phosphate and melphalan in patients undergoing allogeneic hematopoietic stem cell transplantation for advanced, relapsed or refractory hematological malignancies.
- To describe the toxicities of escalating doses of TMLI in these patients.
- To describe the frequency of clinical response in patients treated with this regimen.
- To describe the frequency of primary and secondary engraftment failure in patients treated with this regimen.
- To describe the time to neutrophil and platelet engraftment in patients treated with this regimen.
- To describe the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.
- To describe the overall survival of patients treated with this regimen.
- To describe the progression-free survival of patients treated with this regimen.
OUTLINE: This is a dose-escalation study of intensity-modulated total marrow and lymph node irradiation (TMLI).
- Intensity-modulated radiation therapy: Patients undergo TMLI to skeletal bone/marrow, major lymph node chains, spleen, and liver using helical tomotherapy twice daily on days -6 to -3.
- Reduced-intensity preparative regimen: Patients receive fludarabine phosphate IV on days -6 to -2 and melphalan IV on day -1.
- Hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.
After completion of study treatment, patients are followed periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00800150
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010-3000|
|Principal Investigator:||Joseph Rosenthal, MD||Beckman Research Institute|