Helical Tomotherapy, Fludarabine Phosphate, and Melphalan Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
RATIONALE: Giving chemotherapy drugs, such as fludarabine phosphate and melphalan, and HT before a donor stem cell transplant helps stop the growth of cancer cells. It also helps 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 HT together with fludarabine phosphate and melphalan before a transplant may stop this from happening.
PURPOSE: This clinical trial studies helical tomotherapy (HT), fludarabine phosphate, and melphalan followed by donor stem cell transplant in treating patients with hematologic malignancies.
Drug: fludarabine phosphate
Procedure: allogeneic hematopoietic stem cell transplantation
Radiation: intensity-modulated radiation therapy
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Stem Cell Transplant With a Novel Conditioning Therapy Using Helical Tomotherapy, Melphalan, and Fludarabine in Hematological Malignancies|
- 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 ]Descriptive statistics will be used to summarize data outcomes. The type and grade of toxicities during therapy will be tabulated. Toxicities will be evaluated using the modified Bearman Scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
- 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: 2 years 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 ]
|Study Start Date:||June 2006|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor, radiation therapy, transplant)
PREPARATIVE REGIMEN*: Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. Patients also undergo helical tomotherapy twice daily on days -7 to -4. TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. NOTE: *Treatment begins 2 days earlier in patients receive tacrolimus and/or sirolimus for GVHD prophylaxis.
Drug: fludarabine phosphate
25 mg/m2 day -7 through day -3 prior to transplantDrug: melphalan
140 mg/m2 day -2 prior to transplantProcedure: allogeneic hematopoietic stem cell transplantation
Cells infused on Day 0 of transplant regimenRadiation: intensity-modulated radiation therapy
Each fraction is 150 cGy, 2 fractions each day on day -7 through day -4 prior to transplant
PRIMARY OBJECTIVES: I. To assess the feasibility in terms of toxicity and safety of HT in combination with Fludarabine (fludarabine phosphate) and Melphalan as a preparative regimen for allogeneic stem cell transplantation in patients with Hematological Malignancies: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS).
SECONDARY OBJECTIVES: I. To evaluate within the confines of this pilot study, incidence of neutrophil and platelet engraftment, survival on day +180, the overall survival, and disease free survival in patients with Hematological Malignancies: ALL, AML, and MDS.
II. To evaluate incidence of primary and secondary engraftment failure, incidence of relapse, incidence of acute and chronic transplant related complications, including veno-occlusive disease of the liver (VOD), organ toxicity, secondary malignancies, including treatment-related myelodysplastic syndrome, and acute and chronic graft-versus-host disease (GVHD), as well as post-transplant chimerism.
OUTLINE: PREPARATIVE REGIMEN*: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3 and melphalan IV on day -2. Patients also undergo HT twice daily on days -7 to -4.
TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. NOTE: *Treatment begins 2 days earlier in patients receive tacrolimus and/or sirolimus for GVHD prophylaxis.
After completion of study treatment, patients are followed up periodically for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00544466
|United States, California|
|City of Hope Medical Center|
|Duarte, California, United States, 91010-3000|
|Principal Investigator:||Joseph Rosenthal, MD||City of Hope Medical Center|