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Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 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: August 15, 2016
Last verified: August 2016
  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
Ewing's Family Tumors
Renal Tumors
Hepatoblastoma
Rhabdomyosarcoma
Soft Tissue Sarcoma
Primary Malignant Brain Neoplasms
Retinoblastoma
Medulloblastoma
Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET)
Atypical Teratoid/Rhabdoid Tumor (AT/RT)
CNS Tumors
Germ Cell Tumors
Drug: Ifosfamide
Drug: Etoposide
Drug: Mesna
Biological: G-CSF
Drug: Busulfan
Drug: Melphalan
Drug: Thiotepa
Biological: Autologous stem cell infusion
Radiation: Radiation
Drug: Carboplatin
Drug: Paclitaxel
Procedure: Leukapheresis

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: January 2019
Estimated Primary Completion Date: January 2017 (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
  • Arms A&B: 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
  • Arm C: 2000 mg/m^2 IV daily on Days 1-3 every 14 days for 2 cycles
Other Names:
  • Mitoxana
  • Ifex
Drug: Etoposide
  • Arms A&B: 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.
  • Arm C: 400 mg/m^2 daily on days -4, -3, and -2 every 21 days
Other Names:
  • Eposin
  • Etopophos
  • Vepesid
  • VP-16
Drug: Mesna
  • Arms A&B: 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.
  • Arm C: 2000 mg/m^2 IV daily on Days 1-3 every 14 days for 2 cycles
Other Names:
  • Uromitexan
  • Mesnex
Biological: G-CSF
  • Arms A&B: 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.
  • Arm C: 10 μg/kg subcutaneously daily beginning 6 hours after completion of ifosfamide on day 3 until adequate CD34+ cell collection or day 15, whichever occurs first.
Other Name: Granulocyte colony-stimulating factor
Drug: Busulfan
Arm A: 1.1 mg/kg IV every 6 hours on days -8 through -6
Other Name: Busulfex
Drug: Melphalan
Arm A: 50 mg/m^2 intravenously (IV) over 30 min on Days -4 and -5
Other Name: 50 mg/m2 IV over 30 min
Drug: Thiotepa
Arm A: 250 mg/m^2 intravenously (IV) over 2 hrs on days -2 and -3 Arm B: 10 mg/kg/day or 300 mg/m^2 IV on days -3 and -2
Other Name: Thioplex
Biological: Autologous stem cell infusion
Arms A, B & C: On Day 0, stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.
Radiation: Radiation

Arm A: 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
  • Arms A&B: 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
  • Arm C: 2000 mg/m^2 IV daily on Days 1-3 every 14 days for 2 cycles
Other Names:
  • Mitoxana
  • Ifex
Drug: Etoposide
  • Arms A&B: 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.
  • Arm C: 400 mg/m^2 daily on days -4, -3, and -2 every 21 days
Other Names:
  • Eposin
  • Etopophos
  • Vepesid
  • VP-16
Drug: Mesna
  • Arms A&B: 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.
  • Arm C: 2000 mg/m^2 IV daily on Days 1-3 every 14 days for 2 cycles
Other Names:
  • Uromitexan
  • Mesnex
Biological: G-CSF
  • Arms A&B: 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.
  • Arm C: 10 μg/kg subcutaneously daily beginning 6 hours after completion of ifosfamide on day 3 until adequate CD34+ cell collection or day 15, whichever occurs first.
Other Name: Granulocyte colony-stimulating factor
Drug: Thiotepa
Arm A: 250 mg/m^2 intravenously (IV) over 2 hrs on days -2 and -3 Arm B: 10 mg/kg/day or 300 mg/m^2 IV on days -3 and -2
Other Name: Thioplex
Biological: Autologous stem cell infusion
Arms A, B & C: On Day 0, stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.
Drug: Carboplatin
Arm B: depending on age and GFR 17mg/kg/day IV over 4 hours or 510 mg/m^2/day IV over 4 hours Arm C: AUC=8 daily on days -4, -3, and -2 every 21 days
Other Name: Paraplatin
Arm C: Germ Cell Tumors
  1. High-Dose Chemotherapy (3 cycles)

    • Carboplatin AUC=8 & Etoposide 400 mg/m^2 daily, days -4, -3, and -2 every 21 days
  2. Autologous Stem Cell Infusion ≥ 3 x 106 CD34+ cells/kg Day 0 Cycles 1, 2 and 3
  3. TI Chemotherapy & PBSC Collection.

    • Paclitaxel 200mg/m^2 IV over 3 hours on Day 1 every 14 days for 2 cycles
    • Ifosfamide 2000 mg/m^2 IV daily on Days 1-3 every 14 days for 2 cycles
    • Mesna 2000 mg/m^2 on Days 1-3 every 14 days for 2 cycles
    • G-CSF 10 μg/kg sub q daily on day 3 until adequate CD34+ cell collection or day 15, whichever occurs first
    • Leukapheresis starting on approx. day 11 and continued daily until reaching the collection goal of ≥ 8 x 106 CD34+ cells/kg) or day 15, whichever occurs first
Drug: Ifosfamide
  • Arms A&B: 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
  • Arm C: 2000 mg/m^2 IV daily on Days 1-3 every 14 days for 2 cycles
Other Names:
  • Mitoxana
  • Ifex
Drug: Etoposide
  • Arms A&B: 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.
  • Arm C: 400 mg/m^2 daily on days -4, -3, and -2 every 21 days
Other Names:
  • Eposin
  • Etopophos
  • Vepesid
  • VP-16
Drug: Mesna
  • Arms A&B: 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.
  • Arm C: 2000 mg/m^2 IV daily on Days 1-3 every 14 days for 2 cycles
Other Names:
  • Uromitexan
  • Mesnex
Biological: G-CSF
  • Arms A&B: 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.
  • Arm C: 10 μg/kg subcutaneously daily beginning 6 hours after completion of ifosfamide on day 3 until adequate CD34+ cell collection or day 15, whichever occurs first.
Other Name: Granulocyte colony-stimulating factor
Biological: Autologous stem cell infusion
Arms A, B & C: On Day 0, stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.
Drug: Carboplatin
Arm B: depending on age and GFR 17mg/kg/day IV over 4 hours or 510 mg/m^2/day IV over 4 hours Arm C: AUC=8 daily on days -4, -3, and -2 every 21 days
Other Name: Paraplatin
Drug: Paclitaxel
Arm C: 200 mg/m2 IV over 3 hours on Day 1 every 14 days for 2 cycles
Other Names:
  • Taxol
  • Onxal
Procedure: Leukapheresis
Arm C: Blood will be taken by a needle placed in one arm and processed through a machine, which spins the blood so that the white blood cells will be separated out in the machine for purposes of this research and the rest of the blood will be returned through a needle in the other arm.

  Eligibility

Ages Eligible for Study:   up to 70 Years   (Child, Adult, Senior)
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
    • 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. > 1.5 cm2 residual disease following resection for any Medulloblastoma histology
        2. lumbar CSF cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery
        3. 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).
    • Arm C: Germ Cell Tumors

      • Confirmation of germ cell tumor (GCT) histology (both seminoma and nonseminoma). Tumor may have originated in any primary site. NOTE: In rare circumstances, patients will be allowed to enroll even if a pathologic diagnosis may not have been established. This would require a clinical situation consistent with the diagnosis of GCT (testicular, peritoneal, retroperitoneal or mediastinal mass, elevated tumor marker levels {HCG ≥ 500; AFP ≥ 500} and typical pattern of metastases).

        1. One or more unfavorable prognostic features for achieving a CR with conventional-dose chemotherapy. Unfavorable prognostic features include:
        2. extragonadal primary site
        3. PD following an incomplete response (IR) to first-line therapy,
        4. PD after a conventional-dose salvage (cisplatin + ifosfamide -based) regimen
  • Disease Status at Enrollment:

    • Arms A & B, 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
    • Arm C

      • Evidence of progressive or recurrent GCT (measurable or non-measurable) following one or more cisplatin-based chemotherapy, defined as meeting at least one of the following criteria:

        1. Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT. Patients with incomplete gross resection where viable GCT is found are considered eligible.
        2. Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease.
        3. Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase.
  • Age and Performance Status

    • Arms A & B

      • 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
    • Arm C

      • Age: 0-70 years of age
      • Performance status: Karnofsky Performance Status ≥ 70% for patients > 16 years of age or Lansky Play Score ≥ 70 for patients ≤ 16 years of age
  • Organ Function

    • Arm A

      • 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/1.73m^2 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)
    • Arm B

      • Timing: patients must be fully recovered from radiation, induction chemotherapy or surgery prior to receiving consolidation, with minimum elapsed time of 2 weeks.
      • Hematologic: ANC > 750/µl, hemoglobin of >8 gm/dl (may receive PRBC transfusions) and platelet count > 75,000/µl (transfusion independent).
      • Renal: GFR ≥ 50 ml/min/1.73m^2
      • Hepatic: AST or ALT ≤ 2.5 x ULN and bilirubin ≤ 1.5 x ULN
      • Cardiac: ejection fraction ≥ 45% or no clinical evidence of heart failure
      • Pulmonary: oxygen saturation > 94% at rest (on room air)
      • Central Nervous System: patients with seizure history are allowed if on anti-convulsants and well controlled; patients must not be in status epilepticus, coma or require assisted ventilation
    • Arm C

      • Hematologic: ANC ≥ 750/mm^3, platelets ≥ 75,000/mm^3
      • Renal: GFR ≥ 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
      • Hepatic: AST or ALT ≤ 2.5 x upper limits of normal (ULN), if hepatic involvement < 5 x ULN; bilirubin ≤ 2.0 x upper limits of normal (ULN)
  • Arms A and C: Patients with a history of CNS tumor involvement are eligible if they have completed treatment for CNS disease (radiotherapy or surgery or chemotherapy), have recovered from or stabilization of the side effects associated with the therapy and have no evidence of progressive CNS disease at the time of enrollment

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Active, uncontrolled infection and/or human immunodeficiency virus (HIV) positive constitute progressive disease.
  • Concomitant enrollment on clinical study (such as COG study) that does not allow co-enrollment on this standard of care protocol (Arm B only)
  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

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: August 15, 2016
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:
Neoplasms
Neoplasms, Germ Cell and Embryonal
Sarcoma
Rhabdomyosarcoma
Medulloblastoma
Retinoblastoma
Brain Neoplasms
Rhabdoid Tumor
Central Nervous System Neoplasms
Kidney Neoplasms
Hepatoblastoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Glioma
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Retinal Diseases
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on September 23, 2016