High Dose Chemotherapy and Autologous Transplant for Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell (PBSC) Rescue for Neuroblastoma: Standard of Care Considerations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01526603
• Other study ID #: 2011OC072
• Secondary ID: MT2011-11C
• Status: Completed
• Phase: N/A
• Start date: March 28, 2012
• Est. completion date: May 30, 2023

Study information

• Verified date: February 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: May 30, 2023
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

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.

Biological:
• Autologous stem cell infusion
On day 0 the stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.
• 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.

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.
• 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
• 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

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients with Successful Engraftment	The time to neutrophil engraftment will be assessed by standard statistical approaches.	Day 42
Secondary	Number of Patients with Disease Free Survival	The number of patients alive and disease free will be assessed using standard statistical approaches.	2 Years
Secondary	Overall Survival	The number of patients alive will be assessed by standard statistical approaches.	2 Years
Secondary	Number of Patients with Treatment Related Death	The rate of treatment related mortality will be assessed by cumulative incidence approach.	1 Year
Secondary	Number of Patients with Disease Free Survival	The number of patients alive and disease free will be assessed using standard statistical approaches.	5 Years
Secondary	Overall Survival	The number of patients alive will be assessed by standard statistical approaches.	5 Years