Total Marrow Irradiation Added to an Alkylator-Intense Conditioning Regimen for Patients With High Risk or Relapsed Solid Tumors
RATIONALE: A peripheral blood stem cell transplant or bone marrow transplant using stem cells from the patient may be able to replace immune cells that were destroyed by chemotherapy and image-guided intensity-modulated radiation therapy used to kill tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bone marrow radiation therapy followed by an autologous stem cell transplant in treating patients with high-risk or relapsed solid tumors.
Brain and Central Nervous System Tumors
Procedure: stem cell transplantation
Radiation: total marrow irradiation
Radiation: Whole lung radiation
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Dose Escalation of Total Marrow Irradiation Added to an Alkylator-Intense Conditioning Regimen for Patients With High Risk or Relapsed Solid Tumors|
- Maximum tolerated dose of tomotherapy up to 12 Gy [ Time Frame: Day 42 ] [ Designated as safety issue: Yes ]is a state-of-the- art means of delivering highly conformal radiation to tumors of targeted volume with high therapeutic gain. Tomotherapy offers unique advantages over total body irridiation and is expected to improve clinical outcome. The MTD is defined as the highest dose studied for which the incidence of dose limiting toxicity is less than 33%.
- Percent of patients who had PET scans and "spot radiation" to PET-positive lesions after transplantation [ Time Frame: Day 60 Post Transplant ] [ Designated as safety issue: No ]PET-CT scan is done prior to and after transplant. Radiation is given before and after transplant.
- Change in bone mineral density [ Time Frame: Baseline, 6 and 12 Months Post Transplantation ] [ Designated as safety issue: Yes ]the change in bone density and turnover in patients exposed to alkylator intensive conditioning regimen followed by tomographic total marrow irradiation (TMI).
- Rate of Treatment Related Mortality in Non-TMI Treated Patients [ Time Frame: Day 100 Post Transplant ] [ Designated as safety issue: Yes ]Determined in patients who were not treated with total marrow irradiation; all deaths without previous relapse or progression are usually considered as related to transplantation.
- Rate of Primary Neutrophil Engraftment [ Time Frame: Day 42 ] [ Designated as safety issue: No ]Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.
- Overall Survival [ Time Frame: From date of enrollment to date of death or censored at the date of last documented contact ] [ Designated as safety issue: No ]Determined in patients not receiving total marrow irradiation. The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate.
- Disease-Free Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]In patients not receiving total marrow irradiation, the length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.
|Study Start Date:||August 2005|
|Estimated Study Completion Date:||June 2014|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
Experimental: Total Marrow Irradiation (MTI) with Tomotherapy
TMI given prior to alkylator intensive conditioning regimen (Busulfan 9.6 mg/kg intravenously (IV) (>4 yrs of age) or 13.2 mg/kg IV (< 4 years of age), Melphalan 100 mg/m^2, Thiotepa 500 mg/m^2 for high risk solid tumor patients, Whole lung radiation 1500cGy in 10 fractions by Day 60, stem cell transplantation on day 0. Ifosfamide, etoposide, and mesna are given Days 0-4 followed by filgrastim for 3 doses. Cohorts of patients (n=3) will be treated with increasing doses of TMI (600, 1000, 1200 cGy) directed toward the bones.
Beginning 24 hours after chemotherapy end: 10 microgram/kg/day subcutaneously (SQ) or intravenously (IV) until absolute neutrophile count (ANC) > 1,000/mm^2.
Starting that day, increase dose to 15 microgram/kg/day SQ or IV given as a single injection for 3 doses.
Other Names:Drug: busulfan
Part of pre-transplant conditioning chemotherapy: Administered as Busulfan 9.6 mg/kg IV (>4 yrs of age) or 13.2 mg/kg IV (< 4 years of age),every 6 hours on Days -8 through -6.
Other Names:Drug: etoposide
Part of Mobilization chemotherapy and Peripheral blood progenitor cell collections (day -100 to -30): Given as 100 mg/m^2/day intravenous (IV) over 1 hour for 5 days.
Other Names:Drug: ifosfamide
Part of Mobilization chemotherapy and Peripheral blood progenitor cell collections (day -100 to -30): Given as 1.8 g/m^2/day intravenous (IV) over 1 hour on for 5 days.
Other Names:Drug: melphalan
Part of pre-transplant conditioning chemotherapy: Administered as 100 mg/m^2 intravenous (IV) over 30 min on Days -5 through -4.
Other Name: AlkeranDrug: thiotepa
Part of pre-transplant conditioning chemotherapy: Administered as 500 mg/m^2 intravenously (IV) over 2 hrs on Days -3 through -2.
Other Name: ThioTEPAProcedure: stem cell transplantation
Regardless of whether the patient will be receiving peripheral cells or bone marrow, infusion will be intravenous on day 0, immediately after thawing.
Other Name: HPC infusionRadiation: tomotherapy
Radiation: total marrow irradiation
We plan to deliver the total marrow irradiation (TMI) to the upper half of the body using Tomotherapy TMI as explained in this protocol. However the lower part of the body will be treated with Anterior/Posterior linac based radiation treatment. Tomotherapy will then be delivered at a dose rate so as to keep the total treatment time to no more than 30 minutes. We anticipate that the dose rate will be around 400 cGy
/minute (instantaneous dose rate).
TMI will be delivered to all bony sites as part of the conditioning. Additional "spot" therapy to PET positive lesions, primary disease (if not previously irradiated to maximum tolerated dose), and lungs will be performed on Day +60. Cohorts of 3 patients will be treated at a total dose of 600 cGy, 900 cGy or 1200 cGy on Days -11 through -9.Drug: Mesna
Part of Mobilization chemotherapy and Peripheral blood progenitor cell collections (day -100 to -30): Given as 1.8 g/m^2/day divided in every 6 hrs dosing for 5 days.
Other Names:Radiation: Whole lung radiation
At Day 60, patients with prior lung metastasis should receive whole lung irradiation (1500cGy in 10 fractions).
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00623077
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Michael R. Verneris, MD||Masonic Cancer Center, University of Minnesota|