Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Total Marrow Irradiation Added to an Alkylator-Intense Conditioning Regimen for Patients With High Risk or Relapsed Solid Tumors

This study has been terminated.
(Replaced by another study)
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00623077
First received: February 22, 2008
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Kidney Cancer
Liver Cancer
Retinoblastoma
Sarcoma
Biological: filgrastim
Drug: busulfan
Drug: etoposide
Drug: ifosfamide
Drug: melphalan
Drug: thiotepa
Procedure: stem cell transplantation
Radiation: tomotherapy
Radiation: total marrow irradiation
Drug: Mesna
Radiation: Whole lung radiation
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • 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%.


Secondary Outcome Measures:
  • 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.


Enrollment: 23
Study Start Date: August 2005
Estimated Study Completion Date: June 2014
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: filgrastim

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:
  • G-CSF
  • Sargramostim
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:
  • Busulfex
  • Myleran
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:
  • Eposin
  • VP-16
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:
  • Mitoxana
  • Ifex
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: Alkeran
Drug: 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: ThioTEPA
Procedure: 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 infusion
Radiation: tomotherapy

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).

Radiation: total marrow irradiation
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:
  • Uromitexan®
  • Mesnex
Radiation: Whole lung radiation
At Day 60, patients with prior lung metastasis should receive whole lung irradiation (1500cGy in 10 fractions).

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis Patients must have had histologic verification of malignancy at original diagnosis. Diseases included are:

    • Ewing's Family Tumors (ES/PNET/DSRCT): metastatic at the time of diagnosis and/or relapsed after therapy
    • Renal tumors: relapsed (all histology-Wilm's tumor) or at diagnosis (clear cell sarcoma and Rhabdoid tumor),
    • Hepatoblastoma: metastatic at the time of diagnosis and/or relapsed after therapy
    • Rhabdomyosarcoma: metastatic at the time of diagnosis and/or relapsed after therapy
    • Soft tissue sarcomas: chemotherapy responsive metastatic disease or chemotherapy responsive relapsed disease
    • Primary Malignant Brain Neoplasms at diagnosis and/or relapse
    • Retinoblastoma: disseminated at diagnosis and/or relapsed
    • Other High Risk Metastatic or Relapsed Solid Tumors: To be approved by two or more physicians on the study committee
  • Disease Status: Patients must have either: 1) no evidence of disease or 2) stable, non-progressive disease (defined as non-progressive abnormalities on physical exam or computated tomography (CT) and/or magnetic resonance imaging [MRI]) within 4 weeks of study entry.
  • Age: Patients must be 0-70 years of age at the time of study entry.
  • Performance Level: Karnofsky > or = 50% for patients > 10 years of age and Lansky > or = 50% for patients < or = 10 years of age. Note: Neurologic deficits in patients with central nervous system (CNS) tumors must be stable for a minimum of 1 week prior to study entry.
  • Organ Function:

    • Hematologic: prior to receiving total marrow irradiation (TMI) patients should have a hemoglobin of >10 gm/dl and a platelet count > 20,000/μl. Patients may receive transfusions as necessary.
    • Renal: glomerular flow rate (GFR) ≥ 50 ml/min/1.73m^2 or serum creatinine ≤ 2.5 x upper limit of normal (ULN) for age
    • Hepatic: aspartate aminotransferase/alanine aminotransferase (AST or ALT) ≤ 5 x ULN and bilirubin ≤ 5 x ULN
    • Cardiac: ejection fraction > 45% or no clinical evidence of heart failure
    • Pulmonary: oxygen saturation > 92% at rest (on room air)

Exclusion Criteria:

  • Disease Status: patients with progressive, non-therapy responsive disease will not be eligible.
  • Infection: patients who have active, uncontrolled infections or those who are HIV+.
  • Pregnancy or Breast-Feeding: pregnant or breast-feeding women will not be entered on this study.
  • Prior Radiation Therapy: patients must be eligible to receive TMI via tomographic radiation therapy (as determined by radiation oncology staff). If not eligible (due to extensive prior radiation or other circumstances), patients can be treated on study but will not receive radiation and will be analyzed on a separate arm.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00623077

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Michael R. Verneris, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00623077     History of Changes
Other Study ID Numbers: 2005LS023, UMN-MT2004-30, 0504M69306
Study First Received: February 22, 2008
Last Updated: June 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
childhood hepatoblastoma
recurrent childhood liver cancer
stage IV childhood liver cancer
adult primary liver cancer
previously treated childhood rhabdomyosarcoma
recurrent childhood rhabdomyosarcoma
previously untreated childhood rhabdomyosarcoma
metastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma
recurrent adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
recurrent Wilms tumor and other childhood kidney tumors
stage IV Wilms tumor
stage V Wilms tumor
rhabdoid tumor of the kidney
stage IV renal cell cancer
childhood mixed glioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood ependymoma
recurrent childhood medulloblastoma
recurrent childhood pineoblastoma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway glioma
untreated childhood brain stem glioma
untreated childhood cerebellar astrocytoma
childhood infratentorial ependymoma
childhood supratentorial ependymoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Central Nervous System Neoplasms
Kidney Neoplasms
Liver Neoplasms
Neoplasms
Nervous System Neoplasms
Retinoblastoma
Sarcoma
Adenocarcinoma
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Eye Diseases
Eye Neoplasms
Kidney Diseases
Liver Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Connective and Soft Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Retinal Diseases
Retinal Neoplasms
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on November 25, 2014