High Dose Chemotherapy and Autologous Transplant for Neuroblastoma

• ClinicalTrials.gov Identifier: NCT01526603
• Recruitment Status: Recruiting
• First Posted: February 6, 2012
• Last Update Posted: March 16, 2023
• Sponsor: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
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	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell (PBSC) Rescue for Neuroblastoma: Standard of Care Considerations
• Actual Study Start Date: March 28, 2012
• Estimated Primary Completion Date: February 2024
• Estimated Study Completion Date: February 2024

Arms and Interventions

Arm

Intervention/treatment

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

Outcome Measures

Primary Outcome Measures :

1. Number of Patients with Successful Engraftment [ Time Frame: Day 42 ]
   The time to neutrophil engraftment will be assessed by standard statistical approaches.

Secondary Outcome Measures :

1. Number of Patients with Disease Free Survival [ Time Frame: 2 Years ]
   The number of patients alive and disease free will be assessed using standard statistical approaches.
2. Overall Survival [ Time Frame: 2 Years ]
   The number of patients alive will be assessed by standard statistical approaches.
3. Number of Patients with Treatment Related Death [ Time Frame: 1 Year ]
   The rate of treatment related mortality will be assessed by cumulative incidence approach.
4. Number of Patients with Disease Free Survival [ Time Frame: 5 Years ]
   The number of patients alive and disease free will be assessed using standard statistical approaches.
5. Overall Survival [ Time Frame: 5 Years ]
   The number of patients alive will be assessed by standard statistical approaches.

Eligibility Criteria

• Ages Eligible for Study: up to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

Contacts

Contact: Lisa Burke; 612-273-8482; lburke3@Fairview.org

Locations

United States, Minnesota

Masonic Cancer Center, University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Lisa Burke 612-273-8482 lburke3@Fairview.org

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Ashish Gupta, MBBS, MPH; Masonic Cancer Center, University of Minnesota

More Information

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT01526603
• Other Study ID Numbers: 2011OC072; MT2011-11C ( Other Identifier: Blood and Marrow Transplantation Program )
• First Posted: February 6, 2012
• Last Update Posted: March 16, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

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; Carboplatin; Etoposide; Melphalan; Tretinoin; Isotretinoin; Lenograstim; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic; Keratolytic Agents