Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma
Overview[ - collapse ][ - ]
Purpose | This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma. Giving chemotherapy to the entire body before a stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. |
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Condition | Neuroblastoma |
Intervention | Drug: Cisplatin Drug: Cyclophosphamide Drug: Doxorubicin Drug: Etoposide Drug: Topotecan Drug: Vincristine Radiation: external beam radiation therapy Procedure: PBSC Procedure: ASCT: autologous stem cell transplant (busulfan, melphalan) Drug: Busulfan Drug: Melphalan Drug: Mesna |
Phase | N/A |
Sponsor | Children's Oncology Group |
Responsible Party | Children's Oncology Group |
ClinicalTrials.gov Identifier | NCT01798004 |
First Received | January 6, 2013 |
Last Updated | February 5, 2014 |
Last verified | February 2014 |
Tracking Information[ + expand ][ + ]
First Received Date | January 6, 2013 |
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Last Updated Date | February 5, 2014 |
Start Date | April 2013 |
Estimated Primary Completion Date | Not Provided |
Current Primary Outcome Measures | Number of patients who experience one or more unacceptable toxicities (severe sinusoidal obstruction syndrome [SOS] or grade 4-5 pulmonary toxicity per Common Toxicity Criteria [CTC] v.4.0) during the consolidation phase of therapy [Time Frame: Up to 28 days post-consolidation therapy] [Designated as safety issue: Yes]The primary study endpoint is the tolerability of the BuMel regimen, which will be quantified as the number of patients who experience one or more unacceptable toxicities (severe SOS (Sinusoidal obstruction syndrome) or Grade 4-5 pulmonary toxicity per CTCv.4.0) during the Consolidation phase of therapy. |
Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma |
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Official Title | Pilot Study Using Myeloablative Busulfan/Melphalan (BuMel) Consolidation Following Induction Chemotherapy for Patients With Newly Diagnosed High-Risk Neuroblastoma |
Brief Summary | This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma. Giving chemotherapy to the entire body before a stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. |
Detailed Description | This groupwide pilot study examines the toxicity profile of the Busulfan-Melphalan (BuMel) myeloablative preparative regimen in children and young adults with newly diagnosed high-risk neuroblastoma. The primary objective of the proposed study will be to examine the toxicity profile of this regimen in the context of COG therapy, with specific focus on the incidence and severity of pulmonary and hepatic toxicity. The Induction regimen will be 5 cycles of Induction. Consolidation therapy will consist of 4 doses of busulfan IV given once daily followed by a single dose of melphalan with a rest day prior to and following the melphalan dose. After recovery from Consolidation radiation therapy, patients will be encouraged to participate in clinical trials of ch14.18 immunotherapy (ie, ANBL0032 or other). Additional examinations will include pharmacokinetic measurements of busulfan and melphalan that will be collected and correlated with toxicity and survival. We will examine the ability to perform Curie scoring in real time, within 21 days of scan acquisition. This will be the first prospective use of Curie scoring in a cooperative group setting. This study will examine our ability to perform ALK gene testing prospectively, within 4 to 6 weeks of sample acquisition, by a centralized lab. Aberrations of the ALK gene in neuroblastoma tumors have been reported by multiple investigators, with potential therapeutic implications. Potential targeted inhibitors of ALK aberrations are now available, and may impact future clinical trial designs. In addition, molecular profiling of MYCN non-amplified tumors with a 14-gene signature panel will be performed. This study will test our ability to obtain tumor samples prospectively and identify molecular profiles within 6-8 weeks of sample acquisition which may also impact future clinical trial design. |
Study Type | Interventional |
Study Phase | N/A |
Study Design | Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
Condition | Neuroblastoma |
Intervention | Drug: Cisplatin Cycle 3 and 5: CISplatin: IV over 1 hour Dose: 50 mg/m2/dose. For patients ≤ 12 kg the dose is 1.67 mg/kg/dose. Days: 1-4. Other Names: NSC# 119875Drug: Cyclophosphamide Cycle 1: IV over 15-30 mins - 400 mg/m2/dose or 13.3 mg/kg/dose if pt ≤ 12 kg Cycle 2: IV over 15-30 mins - 400 mg/m2/dose or 13.3 mg/kg/dose if pt ≤ 12 kg Cycle 4: IV over 1- 6 hours - 2100 mg/m2/dose or 70 mg/kg/dose if pt ≤ 12 kg Other Names: NSC# 26271Drug: Doxorubicin IV over 24 hours Dose: 25 mg/m2/dose. For patients ≤ 12 kg the dose administered is 0.83 mg/kg/dose. Days: 1-3 Continuous infusions require administration through a central venous access. Protect diluted solution from sun light. Other Names: NSC# 123127Drug: Etoposide IV over 1- 2 hours Dose: 200 mg/m2/dose. For patients ≤ 12 kg the dose is 6.67 mg/kg/dose. Days: 1-3 Infuse diluted solution (concentration ≤ 0.4 mg/mL) over at least 1-2 hours; slow rate of administration if hypotension occurs. The use of an in-line filter during the infusion is suggested. Other Names: NSC # 141540Drug: Topotecan IV over 30 minutes Dose: 1.2 mg/m2/dose Days: 1-5 Topotecan dosing is based on BSA regardless of age or weight. Other Names: NSC# 609699Drug: Vincristine IV push over 1 minute or infusion via minibag as per institutional policy. Age-based dosing: Age (in months) < 12 Dose 0.017 mg/kg/dose. Age (in months) ≥ 12 and weight > 12 kg Dose 0.67 mg/m2/dose or 0.022 mg/kg/dose [whichever is lower] Age (in months) ≥ 12 and weight ≤ 12 kg Dose 0.022 mg/kg/dose Note: Total dose may NOT exceed 2 mg in 72 hours or 0.67 mg/day for any patient. Administer prior to start of DOXOrubicin infusion and then daily for 3 total doses. Other Names: NSC# 67574Radiation: external beam radiation therapy Radiation will be given after recovery from BuMel transplant. Treatment volumes will be based on post-Induction imaging (MIBG, CT and/or MRI) and operative reports. Organ toxicity within the radiation field should have resolved. It is desirable to start radiation therapy no sooner than Day +28 and by Day +42 following ASCR of the BuMel transplant. Other Names: EBRTProcedure: PBSC Stem cells will be infused on Day 0 of Consolidation therapy. Where the DMSO volume in the stem cell product would exceed accepted level for infusion within a 24 hour period, stem cell products may be infused over 2 days to meet this standard Other Names: PBSC harvest: Peripheral blood stem cell harvest.Procedure: ASCT: autologous stem cell transplant (busulfan, melphalan) Chemotherapy also destroys healthy bone marrow. The blood stem cells that were stored during the Induction phase are given back to the patient after the high-dose chemotherapy. When these cells are given back, the procedure is called an Autologous Stem Cell Transplant (ASCT). Drug: Busulfan Consolidation therapy will consist of 4 doses of busulfan IV given once daily Other Names:
Short IV infusion to be completed in not more than 30 minutes Other Names: NSC#8806Drug: Mesna Mesna is a supportive care drug which is given to help protect your bladder from the side effects of chemotherapy. Induction Cycle 4 (Weeks 10-12) - Mesna: IV over 15 - 30 minutes or by continuous infusion. Other Names:
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Study Arm (s) | Experimental: Treatment (induction therapy, consolidation therapy, ASCT) INDUCTION THERAPY: COURSES 1-2: Cyclophosphamide IV over 15-30 mins and topotecan hydrochloride IV over 30 mins on days 1-5. Day 6 Filgrastim dose. Treatment repeats every 3 wks for 2 courses. COURSES 3 & 5: Cisplatin IV over 1 hr on days 1-4 and etoposide IV over 1-2 hrs on days 1-3. Treatment repeats every 3 wks for 2 courses. COURSE 4: Cyclophosphamide IV over 1-6 hrs days 1-2, vincristine sulfate IV over 1 min days 1-3, & doxorubicin hydrochloride IV over 24 hrs days 1-3. MESNA after chemo. Treatment repeats every 3 wks for 1 course. Treatment continues in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: 4-8 wks following the 5th course of induction therapy, busulfan IV over 3 hrs days -6 to -3 & melphalan IV day -1. Radiation Therapy & ASCT: autologous stem cell transplant (busulfan, melphalan) day 0. PBSC infusion 24 hrs after melphalan infusion. Some patients undergo external beam radiation therapy (EBRT) after induction & consolidation. |
Recruitment Information[ + expand ][ + ]
Recruitment Status | Recruiting |
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Estimated Enrollment | 138 |
Estimated Completion Date | Not Provided |
Estimated Primary Completion Date | January 2015 |
Eligibility Criteria | Inclusion Criteria: - Patients must have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria - Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 are eligible with the following: - MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features - Age > 18 months (> 547 days) regardless of biologic features - Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or any biologic feature that is indeterminate/unsatisfactory/unknown - Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following: - MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features - Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status - Patients with newly diagnosed neuroblastoma with INSS stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features - Patients with newly diagnosed neuroblastoma with INSS Stage 4S with MYCN amplification (> 4-fold increase in MYCN expression signals as compared to reference signals), regardless of additional biologic features - Patients >= 365 days initially diagnosed with neuroblastoma INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; study enrollment on ANBL12P1 must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S - Patients must not have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification status and histology - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows: - Age 1 month to < 6 months: 0.4 mg/dL - Age 6 months to < 1 year: 0.5 mg/dL - Age 1 to < 2 years: 0.6 mg/dL - Age 2 to < 6 years: 0.8 mg/dL - Age 6 to < 10 years: 1 mg/dL - Age 10 to < 13 years: 1.2 mg/dL - Age 13 to < 16 years: 1.5 mg/dL (males), 1.4 mg/dL (females) - Age >= 16 years: 1.7 mg/dL (males), 1.4 mg/dL (females) - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age - Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide evaluation - No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure. Exclusion Criteria: - Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (ie, nonamplified MYCN, favorable pathology, and DNA index > 1) are not eligible - Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events - Lactating females are not eligible unless they have agreed not to breastfeed their infants - Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained - Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation. |
Gender | Both |
Ages | N/A |
Accepts Healthy Volunteers | No |
Contacts | Contact: Meera Raman, MS, PMP, CCRP (626) 241-1532 mraman@childrensoncologygroup.org |
Location Countries | United States |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01798004 |
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Other Study ID Numbers | ANBL12P1 |
Has Data Monitoring Committee | Yes |
Information Provided By | Children's Oncology Group |
Study Sponsor | Children's Oncology Group |
Collaborators | National Cancer Institute (NCI) |
Investigators | Study Chair: Meaghan Granger, MD Cook Children's Medical Center |
Verification Date | February 2014 |
Locations[ + expand ][ + ]
Children's Oncology Group | Arcadia, California, United States, 91006-3776 Contact: Mary M Granger | 215-590-6359Principal Investigator: Mary M Granger Recruiting |
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