Dose Escalation of Total Marrow Irradiation Added to an Alkylator-Intense Conditioning Regimen for Patients With High Risk or Relapsed Solid Tumors
- To determine the maximum tolerated dose of tomographic total marrow irradiation (TMI)
when given prior to an alkylator-intensive conditioning regimen in patients with
high-risk or relapsed solid tumors.
- To determine the feasibility of performing positron emission tomography (PET) scans and
spot radiation to PET-positive lesions after transplantation.
- To determine the change in bone mineral density and turnover in patients treated with
an alkylator-intensive conditioning regimen and TMI.
- Mobilization chemotherapy and peripheral blood progenitor cell (PBPC) collection:
Patients receive ifosfamide intravenously (IV) and etoposide IV on days -100 through
Beginning 24 hours after completion of chemotherapy, patients receive filgrastim (G-CSF)
subcutaneously (SC) or IV until blood counts recover. Patients then receive an increased
dose of G-CSF SC or IV once daily for 3 consecutive days. Beginning on day -97, patients
undergo up to 4 collections of PBPCs. Patients who do not yield an adequate number of cells
undergo bone marrow harvest.
- Bone marrow harvest: Patients undergo bone marrow aspirate and biopsy 2 weeks after the
last dose of G-CSF. If the aspirate or biopsy is morphologically free of tumor cells
and demonstrates > 20% cellularity, then patients receive sargramostim (GM-CSF) daily
for 5 days followed by bone marrow harvest.
- Total marrow irradiation (TMI) with tomotherapy: Patients undergo escalating doses of
TMI* to all bony sites using helical tomotherapy image-guided intensity-modulated
radiotherapy on days -11 to -9.
NOTE: *Patients with primary CNS tumors do not receive TMI but are eligible to receive
chemotherapy and hematopoietic progenitor cell rescue in accordance with the protocol.
- Conditioning regimen: Patients receive busulfan IV over 2 hours four times daily on
days -8 to -6, high-dose melphalan IV over 30 minutes on days -5 to -4, and thiotepa IV
over 2 hours on days -3 to -2.
- Autologous CD34+ hematopoietic progenitor cell transplantation: Patients undergo
reinfusion of autologous G-CSF-mobilized peripheral blood or bone marrow progenitor
cells on day 0. Patients also receive G-CSF support beginning on day 0 and continuing
until blood counts recover for 2 consecutive days.
- Post-transplantation radiotherapy: Patients may receive additional radiotherapy to
areas of known metastatic disease, PET-positive lesions, primary disease (if not
previously irradiated to maximum tolerated dose), and lungs beginning on day 60 post
transplantation. Patients with prior lung metastasis may receive up to 10 fractions of
Patients may also receive additional radiotherapy to primary disease if maximum tolerated
dose has not yet been reached.
Patients undergo bone mineral density studies at baseline and at days 60, 120, and 180 post
transplantation. Patients also undergo blood sample collection periodically during study for
pharmacokinetic analysis of busulfan.
Patients undergo PET scans at baseline and on day 60.
After completion of study therapy, patients are followed at days 180 and 365 and then
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of tomotherapy up to 12 Gy
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%.
Michael R. Verneris, MD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
|Masonic Cancer Center at University of Minnesota||Minneapolis, Minnesota 55455|