High Dose Chemotherapy and Autologous Transplant for Neuroblastoma

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Recruiting

CT.gov ID

NCT01526603

Collaborator

(none)

Enrollment

Location

Arm

130.2

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

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	N/A

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

Anticipated 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 :

Mar 28, 2012

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: 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 Names: 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 Names: 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 Names: 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 Names: 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

Arm

Intervention/Treatment

Other: 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 Names:

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 Names:

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 Names:

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 Names:

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

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.