High Dose Chemotherapy and Autologous Transplant for Neuroblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01526603
First received: January 31, 2012
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

This is a standard of care document, outlining the therapy for children with high risk neuroblastoma who are not eligible for Children's Oncology Group (COG) studies.


Condition Intervention
Neuroblastoma
Drug: Carboplatin
Biological: Autologous stem cell infusion
Biological: Granulocyte colony stimulating factor
Radiation: Radiation therapy
Drug: Isotretinoin (13-cis-retinoic acid)
Drug: Melphalan
Drug: Etoposide

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell (PBSC) Rescue for Neuroblastoma: Standard of Care Considerations

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Patients with Successful Engraftment [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    The time to neutrophil engraftment will be assessed by standard statistical approaches.


Secondary Outcome Measures:
  • Number of Patients with Disease Free Survival [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    The number of patients alive and disease free will be assessed using standard statistical approaches.

  • Overall Survival [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    The number of patients alive will be assessed by standard statistical approaches.

  • Number of Patients with Treatment Related Death [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    The rate of treatment related mortality will be assessed by cumulative incidence approach.

  • Number of Patients with Disease Free Survival [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    The number of patients alive and disease free will be assessed using standard statistical approaches.

  • Overall Survival [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    The number of patients alive will be assessed by standard statistical approaches.


Estimated Enrollment: 20
Study Start Date: March 2012
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Patients Treated for Neuroblastoma
According to patient weight and renal function, consolidation chemotherapy using various doses of Melphalan, Etoposide, and Carboplatin followed by autologous stem cell infusion and serial post-transplant Granulocyte Colony Stimulating Factor, radiation therapy and Isotretinoin maintenance therapy.
Drug: Carboplatin
Carboplatin intravenously (IV), 425 mg/m2/dose (or if ≤ 12kg, 14.2 mg/kg/dose) once daily x 4 doses on days 7 through 4 pretransplant.
Other Name: Paraplatin
Biological: Autologous stem cell infusion
On day 0 the stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.
Biological: Granulocyte colony stimulating factor
Beginning on day 0 after infusion of the PBSC, patients will receive G-CSF subcutaneously (SQ) or IV (SQ preferred) 5 micrograms/kg once daily and continuing once daily until post-nadir absolute neutrophil count (ANC) > 2000/μL for 3 consecutive days.
Other Name: G-CSF
Radiation: Radiation therapy
It is suggested that patients who have a complete surgical resection of the primary tumor receive 21.6 Gy external beam radiation therapy (EBRT) to the post-induction chemotherapy, pre-operative primary tumor volume. It is suggested that patients who have an incomplete surgical resection of the primary tumor (residual soft tissue mass measuring >1 cm3) will receive 21.6 Gy EBRT to the postinduction chemotherapy, pre-operative primary tumor volume and an additional boost of 14.4 Gy EBRT to the gross residual tumor (total dose 36 Gy to gross residual tumor volume). Radiation should be given after stem cell transplantation and should start no sooner than 28 days post transplant.
Drug: Isotretinoin (13-cis-retinoic acid)
Post-transplant maintenance therapy with cis-RA daily for 14 days every 28 days repeated for 6 months. This phase of the therapy can be initiated by the BMT team and continued by the referring physician. It is recommended to begin Isotretinoin at day 66 post-transplant and no later than day 100. For patients ≤12 kg, isotretinoin (accutane) should be administered at 5.33 mg/kg/dose divided twice daily. For patients >12 kg isotretinoin (accutane) should be administered at 160 mg/m^2/day divided twice a day. Patients should be considered for monoclonal antibody therapy against GD2, such as ch14.18 if such trials are available.
Other Name: Accutane
Drug: Melphalan
Melphalan Intravenously (IV), 70 mg/m2/dose (or if ≤ 12 kg, 2.3 mg/kg/dose) once daily x 3 doses on days 7 through 5 pretransplant
Other Name: Alkeran
Drug: Etoposide
Etoposide intravenously (IV), 338 mg/m2/dose (or if ≤ 12kg, 11.3 mg/kg/dose) once daily x 4 doses on days 7 through 4 pretransplant
Other Names:
  • Eposin
  • VP-16

Detailed Description:

This therapy involves the use of melphalan, etoposide, and carboplatin (consolidation chemotherapy); autologous stem cell rescue, post-transplant radiation therapy and a maintenance phase with Isotretinoin (Accutane, 13-cis-retinoic acid) therapy. If available, patients should also consider post-transplant therapy with cytokines and monoclonal antibody (ch14.18) on a COG or New Approaches to Neuroblastoma Therapy (NANT) trial.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Less than 30 years of age at diagnosis of neuroblastoma
  • No evidence of disease progression: defined as increase in tumor size of >25% or new lesions
  • Recovery from last induction course of chemotherapy (absolute neutrophil count > 500 and platelet > 20,000)
  • No uncontrolled infection
  • Minimum frozen peripheral blood stem cells (PBSCs) of 2 x 10^6 CD34 cells/kg for transplant are mandatory and 2 x 10^6 CD34 cells/kg for back-up are strongly recommended (thus, PBSC of 4 x 106 CD34 cells/kg is encouraged)
  • Adequate organ function defined as:

    • Hepatic: aspartate aminotransferase (AST) < 3 x upper limit of institutional normal 8 Cardiac: shortening fraction ≥ 27% or ejection fraction ≥ 50%, no clinical congestive heart failure 8 Renal: Creatinine clearance or glomerular filtration rate (GFR) > 60 mL/min/1.73m^2 If a creatinine clearance is performed at end induction and the result is < 100 ml/min/1.73m^2, a GFR must then be performed using a nuclear blood sampling method or iothalamate clearance method. Camera method is NOT allowed as measure of GFR prior to or during Consolidation therapy for patients with GFR or creatinine clearance of < 100 ml/min/1.73m^2

Exclusion Criteria

  • Patients with progressive disease should consider participating in phase I studies since consolidation therapy using the regimen outlined in this document have not been determined to be useful.
  • Patients who are delayed in consolidation chemotherapy beyond 8 weeks, and don't meet organ function criteria.
  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: NCT01526603

Contacts
Contact: Patricia Kleinke 612-273-0857 pkleink1@fairview.org

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Michael R. Verneris, M.D.    612-626-2961    verneris@umn.edu   
Principal Investigator: Michael R. Verneris, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Michael R. 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: NCT01526603     History of Changes
Other Study ID Numbers: 2011OC072, MT2011-11C
Study First Received: January 31, 2012
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
peripheral blood stem cell transplantation
autologous stem cell transplant

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Etoposide
Etoposide phosphate
Melphalan
Tretinoin
Carboplatin
Isotretinoin
Lenograstim
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Keratolytic Agents

ClinicalTrials.gov processed this record on July 23, 2014