Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01505569
First received: January 4, 2012
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

This is a standard of care treatment guideline for high risk or relapsed solid tumors or CNS tumors consisting of a busulfan, melphalan, thiotepa conditioning (for solid tumors) or carboplatin and thiotepa conditioning (for CNS tumors) followed by an autologous peripheral blood stem cell transplant. For solid tumors, if appropriate, disease specific radiation therapy at day +60. For CNS tumors, the conditioning regimen and autologous peripheral blood stem cell transplant will be given for 3 cycles.


Condition Intervention
Hematopoietic Stem Cell Transplantation
Solid Tumor
Transplantation, Autologous
Drug: Ifosfamide
Drug: Etoposide phosphate
Drug: Mesna
Biological: Granulocyte colony-stimulating factor
Drug: Busulfan
Drug: Melphalan
Drug: Thiotepa
Biological: Autologous stem cell infusion
Radiation: Radiation
Drug: Caboplatin

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Alkylator-Intense Conditioning Followed by Autologous Transplantation for Patients With High Risk or Relapsed Solid or CNS Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Number of patients who have received autologous transplant for high risk or relapsed solid tumor and certain CNS tumors and are alive at 1 year.


Secondary Outcome Measures:
  • Number of Patients Who Achieved Transplant Engraftment [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Engraftment is defined as absolute neutrophil recovery > 500 cells/ul.

  • Disease Free Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Number of patients who do not have evidence of disease returning after transplant (alive and in remission).

  • Treatment-Related Mortality [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Number of patients died due to treatment received.

  • Disease Free Survival [ Time Frame: 3 Years ] [ Designated as safety issue: No ]
    Number of patients who do not have evidence of disease returning after transplant (alive and in remission).


Estimated Enrollment: 20
Study Start Date: October 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm A: Patients with High Risk or Relapsed Solid Tumor
Treatment consists of a mobilization chemotherapy (ifosfamide 1.8 g/m^2/day intravenously [IV], etoposide 100 mg/mg^2 IV, mesna 1.8 g/m^2 divided in every 6 hours dosing, and granulocyte colony stimulating factor 10 mcg/kg subcutaneously or IV until absolute neutrophils > 1,000/mm^2) for 5 days in a 30-100 day pretransplant window, busulfan (1.1 mg/kg IV every 6 hours on days -8 through -6), melphalan (50 mg/mg^2 on days -5 and -4), thiotepa conditioning (250 mg/m^2 IV over 2 hours on days -3 and -2) followed by an autologous peripheral blood stem cell transplant (infusion on Day 0) and, if appropriate, disease specific radiation therapy at day +60.
Drug: Ifosfamide

Ifosfamide 1.8 g/m^2/day intravenously (IV) over

1 hour; given in a window of 30-100 days before transplant for 5 days before conditioning regimen

Other Names:
  • Mitoxana
  • Ifex
Drug: Etoposide phosphate
Etoposide 100 mg/m^2/day intravenously (IV) over 1 hour; given in a window of 30-100 days before transplant for 5 days prior to conditioning regimen.
Other Names:
  • Eposin
  • Etopophos
  • Vepesid
  • VP-16
Drug: Mesna
Mesna 1.8 g/m^2/day divided in every 6 hrs dosing; given in a window of 30-100 days before transplant for 5 days prior to conditioning regimen.
Other Names:
  • Uromitexan
  • Mesnex
Biological: Granulocyte colony-stimulating factor
Beginning 24 hours after treatment with ifosfamide, etoposide and mesna, administer 10 mcg/kg/day subcutaneously (SQ) or intravenously (IV) until absolute neutrophil count (ANC) is greater than (>) 1,000/mm^2. Starting that day, increase dose to 15 mcg/kg/day SQ or IV given as a single injection for 3 doses. All patients should receive G-CSF, 5 ug/kg/day IV as a bolus injection each evening beginning on day 0 until the ANC is >2500 x 10^9/L for 2 consecutive days. G-CSF will subsequently be restarted at 5 ug/kg/day SC or IV if the ANC falls below 1000/mm^3.
Other Name: G-CSF
Drug: Busulfan
Pretransplant conditioning regimen: if <12 kg, 1.1 mg/kg intravenously (IV) every 6 hours,if ≥ 12 kg, 0.8 mg/kg IV every 6 hours on Days 6-8 pretransplant.
Other Name: Busulfex
Drug: Melphalan
Pretransplant conditioning regimen: 50 mg/m^2 intravenously (IV) over 30 min on Days 4 and 5 pretransplant.
Other Name: 50 mg/m2 IV over 30 min
Drug: Thiotepa
Pretransplant conditioning regimen: 250 mg/m^2 intravenously (IV) over 2 hrs on days 2 and 3 before transplant.
Other Name: Thioplex
Biological: Autologous stem cell infusion
On Day 0, stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.
Radiation: Radiation
If a patient is considered for post-transplant irradiation, a disease appropriate full tumor restaging should be done prior to starting. Whole lung irradiation (1500cGy in 10 fractions) may be given in patients with prior lung metastasis. Areas of known metastatic disease or PET areas may receive "spot" irradiation using a dose and method determined to be tolerable by radiation oncology staff. Additional radiation will be given if primary disease has not been irradiated to maximum tolerated dose.
Arm B: Certain CNS Tumors
Treatment consists of a mobilization chemotherapy (ifosfamide 1.8 g/m^2/day intravenously [IV], etoposide 100 mg/mg^2 IV, mesna 1.8 g/m^2 divided in every 6 hours dosing, and granulocyte colony stimulating factor 10 mcg/kg subcutaneously or IV until absolute neutrophils > 1,000/mm^2) for 5 days in a 30-100 day pretransplant window, carboplatin (dose based on GFR and age 17 mg/kg/day IV or 510 mg/m^2/day IV) , thiotepa conditioning (10 mg/kg/day or 300 mg/m^2 IV on days -3 and -2) followed by an autologous peripheral blood stem cell transplant (infusion on Day 0). This will be repeated up to 2 additional 30 day cycles.
Drug: Ifosfamide

Ifosfamide 1.8 g/m^2/day intravenously (IV) over

1 hour; given in a window of 30-100 days before transplant for 5 days before conditioning regimen

Other Names:
  • Mitoxana
  • Ifex
Drug: Etoposide phosphate
Etoposide 100 mg/m^2/day intravenously (IV) over 1 hour; given in a window of 30-100 days before transplant for 5 days prior to conditioning regimen.
Other Names:
  • Eposin
  • Etopophos
  • Vepesid
  • VP-16
Drug: Mesna
Mesna 1.8 g/m^2/day divided in every 6 hrs dosing; given in a window of 30-100 days before transplant for 5 days prior to conditioning regimen.
Other Names:
  • Uromitexan
  • Mesnex
Biological: Granulocyte colony-stimulating factor
Beginning 24 hours after treatment with ifosfamide, etoposide and mesna, administer 10 mcg/kg/day subcutaneously (SQ) or intravenously (IV) until absolute neutrophil count (ANC) is greater than (>) 1,000/mm^2. Starting that day, increase dose to 15 mcg/kg/day SQ or IV given as a single injection for 3 doses. All patients should receive G-CSF, 5 ug/kg/day IV as a bolus injection each evening beginning on day 0 until the ANC is >2500 x 10^9/L for 2 consecutive days. G-CSF will subsequently be restarted at 5 ug/kg/day SC or IV if the ANC falls below 1000/mm^3.
Other Name: G-CSF
Drug: Thiotepa
Pretransplant conditioning regimen: 250 mg/m^2 intravenously (IV) over 2 hrs on days 2 and 3 before transplant.
Other Name: Thioplex
Biological: Autologous stem cell infusion
On Day 0, stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.
Drug: Caboplatin
For the CNS arm, depending on age and GFR 17mg/kg/day IV over 4 hours or 510 mg/m^2/day IV over 4 hours

  Eligibility

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

Inclusion Criteria:

All patients must have histological verification of malignancy at original diagnosis.

  • Eligible Diseases: Arm A Solid Tumor

    • Ewing's Family Tumors (ES/PNET/DSRCT) - metastatic at 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 time of diagnosis and/or relapsed after therapy
    • Rhabdomyosarcoma - metastatic at time of diagnosis and/or relapsed after therapy
    • Soft Tissue Sarcoma - chemotherapy responsive metastatic disease or chemotherapy responsive relapsed disease
    • Primary Malignant Brain Neoplasms <18 years of age - at diagnosis and/or relapse
    • Retinoblastoma - disseminated at diagnosis and/or relapsed
    • Other High Risk Metastatic or Relapsed Solid Tumors - to be approved by 2 or more pediatric hematology/oncology and bone marrow transplant (BMT) physicians
  • Eligible Diseases: Arm B Certain CNS tumors

    • Medulloblastoma: Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) who have high risk Medulloblastoma, defined as any one of the following:
  • > 1.5 cm2 residual disease following resection for any Medulloblastoma histology
  • lumbar CSF cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery
  • MRI evidence of (a) gross nodular seeding in the intracranial subarachnoid space or ventricular system distant from primary tumor site, M2; or (b) gross nodular seeding in the spinal subarachnoid space +/- evidence of intracranial seeding, M3; or (c) extraneural metastases, M4,
  • Anaplastic Histologic Variant Medulloblastoma: less than 70 years of age, any metastatic stage, with total or sub-total resection.
  • Infant Medulloblastoma: Children less than 8 months of age at the time of definitive surgery (for histopathologic diagnosis), any histology, any metastatic state, with total or sub-total resection.
  • Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET): Children less than 36 months (3 years) of age at time of definitive surgery (for histopathologic diagnosis) with or without metastatic disease
  • Atypical Teratoid/Rhabdoid Tumor (AT/RT): less than 70 years of age with CNS AT/RT (with or without metastatic disease).
  • Other High Risk CNS Tumors - to be approved by 2 or more physicians (at least one oncologist and one BMT physician).
  • Disease Status at Enrollment must have fit one of the following:

    • no evidence of disease or
    • stable, non-progressive disease (defined as non-progressive abnormalities on physical exam or CT and/or MRI) within 4 weeks of study entry
  • Age and Performance Status

    • Age: 0 - 70 years
    • Performance status: Karnofsky Performance Status at least 50% for patients > 16 years of age or Lansky Play Score at least 50 for patients less than or equal to 16 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: hemoglobin of >9 gm/dl and platelet count > 20,000/μl. Patients may receive transfusions as necessary.
    • Renal: Glomerular Filtration Rate (GFR) ≥ 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x upper limit of normal (ULN) for age
    • Hepatic: aspartate aminotransferase or 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:

  • Pregnant or breastfeeding
  • Active, uncontrolled infection and/or human immunodeficiency virus (HIV) positive
  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: NCT01505569

Contacts
Contact: Patricia Kleinke, RN 612-273-2800 pkleink1@fairview.org

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Michael Verneris, M.D.    612-626-2961    verneris@umn.edu   
Contact: Patricia Kleinke, RN    612-273-2800    pkleink1@fairview.org   
Principal Investigator: Michael Verneris, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Michael Verneris, M.D. Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01505569     History of Changes
Other Study ID Numbers: 2011OC057, MT2011-09C
Study First Received: January 4, 2012
Last Updated: March 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
autologous transplantation
high risk solid tumor
relapsed solid tumor

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Mesna
Busulfan
Ifosfamide
Isophosphamide mustard
Melphalan
Thiotepa
Etoposide phosphate
Etoposide
Lenograstim
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on August 21, 2014