Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00004188
Status:
COMPLETED
Last Update Posted:
2013-05-17
First Post:
2000-01-21
Brief Title:
Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Neuroblastoma
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
A Randomized Study of Purged Versus Unpurged Peripheral Blood Stem Cell Transplant Following Dose Intensive Induction Therapy for High Risk Neuroblastoma
Status:
COMPLETED
Status Verified Date:
2013-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells
PURPOSE This randomized phase III trial is studying peripheral stem cell transplantation with treated peripheral stem cells following combination chemotherapy to see how well it works compared to peripheral stem cell transplantation with untreated peripheral stem cells following combination chemotherapy in treating patients with neuroblastoma
PURPOSE This randomized phase III trial is studying peripheral stem cell transplantation with treated peripheral stem cells following combination chemotherapy to see how well it works compared to peripheral stem cell transplantation with untreated peripheral stem cells following combination chemotherapy in treating patients with neuroblastoma
Detailed Description:
OBJECTIVES
Primary
Compare the event-free survival in patients with newly diagnosed high risk neuroblastoma or ganglioneuroblastoma treated with myeloablative consolidation chemotherapy and autologous purged versus unpurged peripheral blood stem cells PBSC
Compare the time to engraftment and CD34 content and tumor content by reverse transcriptase polymerase chain reaction RT-PCR of purged versus unpurged PBSC in patients treated with these regimens
Determine event-free survival of patients treated with dose intensive induction chemotherapy comprising cyclophosphamide doxorubicin and vincristine alternating with cisplatin and etoposide
Determine the toxicity of this dose-intensive induction chemotherapy regimen in these patients
Evaluate tumor resectability at second look or delayed surgery response complete response and very good partial response at completion of induction therapy tumor content of peripheral blood and bone marrow and the comparison of historical data from CCG-3891 induction therapy in these patients
Secondary
Compare the toxicity of this myeloablative consolidation regimen using purged vs unpurged PBSC in these patients
Determine if event-free survival is predictable by RT-PCR positivity of the stem cell minimal residual disease in bone marrow and peripheral blood after transplantation by immunocytology and extent of disease as measured by MIBG after transplantation in patients treated with these regimens
Evaluate the prognostic impact of tumor biology on event free survival in patients treated with these regimens
Determine the incidence of relapse in the primary site after radiotherapy and in irradiated versus unirradiated metastatic sites in these patients
Assess the toxicity and tolerability of maintenance therapy with topotecan and cyclophosphamide after intensive induction therapy in patients who decline or are unable to receive myeloablative therapy
Determine the health-related quality of life of patients treated with these regimens
Compare late effects of these regimens on the growth endocrine pulmonary and cardiac function of these patients vs general population standards
Determine the incidence of second malignant neoplasms in patients treated with these regimens
Determine the variability of isotretinoin pharmacokinetics and relationship to pharmacogenomic parameters in these patients
Correlate the isotretinoin pharmacokinetics and pharmacogenomic parameters andor genetic variations in isotretinoin metabolic enzymes with event-free survival or systemic toxicity in these patients
OUTLINE This is a randomized study Patients are randomized to one of two treatment arms for peripheral blood stem cell PBSC collection
All patients receive induction chemotherapy comprising cyclophosphamide IV over 6 hours on days 0 and 1 doxorubicin IV and vincristine IV continuously over 72 hours on days 0-2 and filgrastim G-CSF subcutaneously SC or IV beginning on day 3 and continuing until blood counts recover for courses 1 2 4 and 6 Treatment alternates with courses 3 and 5 comprising etoposide IV over 2 hours on days 0-2 cisplatin IV over 1 hour on days 0-3 and G-CSF SC or IV beginning on day 4 and continuing until blood counts recover Induction chemotherapy repeats every 3 weeks or when blood counts recover in the absence of disease progression or unacceptable toxicity
After course 2 or 3 of induction chemotherapy patients undergo PBSC collection either purged or unpurged depending on randomization Patients continue on daily G-CSF until cell collection is complete
Arm I Patients undergo unpurged PBSC collection until the target cell count is reached
Arm II Patients undergo purged PBSC collection until the target cell count is reached
Patients with immunocytology positive PBSC undergo purged autologous bone marrow collection or repeat purged or unpurged PBSC collection depending on individual patient characteristics
All patients undergo delayed surgical resection of the residual tumor after course 5 of induction chemotherapy
After induction therapy patients achieving complete response very good partial response or partial response receive consolidation therapy comprising melphalan IV on days -7 to -5 followed by carboplatin IV and etoposide IV continuously over days -7 to -4 Patients receive purged or unpurged PBSC infusion or purged autologous bone marrow transplantation on day 0 followed by G-CSF SC or IV beginning 4 hours after completion of transplantation and continuing until blood counts recover Beginning on day 66 patients receive oral isotretinoin twice daily for 14 days Isotretinoin therapy repeats every 4 weeks for 6 courses
After completion of consolidation at least 28 days from stem cell infusion all patients receive local radiotherapy daily over 7 days
Patients not undergoing transplantation or who are ineligible for consolidation therapy receive maintenance therapy comprising cyclophosphamide IV over 30 minutes followed by topotecan IV over 30 minutes on days 0-4 Patients receive G-CSF SC or IV beginning on day 5 and continuing until blood counts recover Maintenance therapy repeats every 3 weeks for 3 courses After completion of maintenance therapy patients receive radiotherapy as outlined above Patients then receive oral isotretinoin twice daily for 14 days Isotretinoin therapy repeats every 4 weeks for 6 courses
Quality of life is assessed at 1 and 5 years
Patients are followed every 3 months for 1 year every 6 months for 4 years and then annually thereafter or until disease progression
NOTE Patients under 5 years of age at 1 year are not assessed until 5 years
PROJECTED ACCRUAL A total of 486 patients will be accrued for this study within 4 years
Primary
Compare the event-free survival in patients with newly diagnosed high risk neuroblastoma or ganglioneuroblastoma treated with myeloablative consolidation chemotherapy and autologous purged versus unpurged peripheral blood stem cells PBSC
Compare the time to engraftment and CD34 content and tumor content by reverse transcriptase polymerase chain reaction RT-PCR of purged versus unpurged PBSC in patients treated with these regimens
Determine event-free survival of patients treated with dose intensive induction chemotherapy comprising cyclophosphamide doxorubicin and vincristine alternating with cisplatin and etoposide
Determine the toxicity of this dose-intensive induction chemotherapy regimen in these patients
Evaluate tumor resectability at second look or delayed surgery response complete response and very good partial response at completion of induction therapy tumor content of peripheral blood and bone marrow and the comparison of historical data from CCG-3891 induction therapy in these patients
Secondary
Compare the toxicity of this myeloablative consolidation regimen using purged vs unpurged PBSC in these patients
Determine if event-free survival is predictable by RT-PCR positivity of the stem cell minimal residual disease in bone marrow and peripheral blood after transplantation by immunocytology and extent of disease as measured by MIBG after transplantation in patients treated with these regimens
Evaluate the prognostic impact of tumor biology on event free survival in patients treated with these regimens
Determine the incidence of relapse in the primary site after radiotherapy and in irradiated versus unirradiated metastatic sites in these patients
Assess the toxicity and tolerability of maintenance therapy with topotecan and cyclophosphamide after intensive induction therapy in patients who decline or are unable to receive myeloablative therapy
Determine the health-related quality of life of patients treated with these regimens
Compare late effects of these regimens on the growth endocrine pulmonary and cardiac function of these patients vs general population standards
Determine the incidence of second malignant neoplasms in patients treated with these regimens
Determine the variability of isotretinoin pharmacokinetics and relationship to pharmacogenomic parameters in these patients
Correlate the isotretinoin pharmacokinetics and pharmacogenomic parameters andor genetic variations in isotretinoin metabolic enzymes with event-free survival or systemic toxicity in these patients
OUTLINE This is a randomized study Patients are randomized to one of two treatment arms for peripheral blood stem cell PBSC collection
All patients receive induction chemotherapy comprising cyclophosphamide IV over 6 hours on days 0 and 1 doxorubicin IV and vincristine IV continuously over 72 hours on days 0-2 and filgrastim G-CSF subcutaneously SC or IV beginning on day 3 and continuing until blood counts recover for courses 1 2 4 and 6 Treatment alternates with courses 3 and 5 comprising etoposide IV over 2 hours on days 0-2 cisplatin IV over 1 hour on days 0-3 and G-CSF SC or IV beginning on day 4 and continuing until blood counts recover Induction chemotherapy repeats every 3 weeks or when blood counts recover in the absence of disease progression or unacceptable toxicity
After course 2 or 3 of induction chemotherapy patients undergo PBSC collection either purged or unpurged depending on randomization Patients continue on daily G-CSF until cell collection is complete
Arm I Patients undergo unpurged PBSC collection until the target cell count is reached
Arm II Patients undergo purged PBSC collection until the target cell count is reached
Patients with immunocytology positive PBSC undergo purged autologous bone marrow collection or repeat purged or unpurged PBSC collection depending on individual patient characteristics
All patients undergo delayed surgical resection of the residual tumor after course 5 of induction chemotherapy
After induction therapy patients achieving complete response very good partial response or partial response receive consolidation therapy comprising melphalan IV on days -7 to -5 followed by carboplatin IV and etoposide IV continuously over days -7 to -4 Patients receive purged or unpurged PBSC infusion or purged autologous bone marrow transplantation on day 0 followed by G-CSF SC or IV beginning 4 hours after completion of transplantation and continuing until blood counts recover Beginning on day 66 patients receive oral isotretinoin twice daily for 14 days Isotretinoin therapy repeats every 4 weeks for 6 courses
After completion of consolidation at least 28 days from stem cell infusion all patients receive local radiotherapy daily over 7 days
Patients not undergoing transplantation or who are ineligible for consolidation therapy receive maintenance therapy comprising cyclophosphamide IV over 30 minutes followed by topotecan IV over 30 minutes on days 0-4 Patients receive G-CSF SC or IV beginning on day 5 and continuing until blood counts recover Maintenance therapy repeats every 3 weeks for 3 courses After completion of maintenance therapy patients receive radiotherapy as outlined above Patients then receive oral isotretinoin twice daily for 14 days Isotretinoin therapy repeats every 4 weeks for 6 courses
Quality of life is assessed at 1 and 5 years
Patients are followed every 3 months for 1 year every 6 months for 4 years and then annually thereafter or until disease progression
NOTE Patients under 5 years of age at 1 year are not assessed until 5 years
PROJECTED ACCRUAL A total of 486 patients will be accrued for this study within 4 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CDR0000067429 | OTHER | Clinical Trialsgov | None |
| COG-A3973 | OTHER | None | None |
| CCG-A3973 | OTHER | None | None |
| POG-A3973 | OTHER | None | None |
| CCG-39703 | OTHER | None | None |
| FHCRC-163100 | None | None | None |