Open / Closed to Recruitment. POSCU Involvement. Diagnosis Trial Oral Chemo Protocol Title Bone

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This list covers the Principal Treatment Centre (Alder Hey) and POSCUs including community services. It covers solid tumour oncology and haemato oncology clinical management protocols and agreed chemotherapy protocols/regimens and specifies those that are deliverable in the community. (Measures 14 7A 113, 14 7B 129, 14 6A 201, 14 7C 122, 14 7C 222). List is correct May 2016 More detailed regimen specific information is available from, R & D Alder Hey approved Trust protocols and the Alder Hey PTC Trial Protocols Diagnosis Trial Oral Chemo Protocol Title Bone Ewing sarcoma Euro Ewing 2012 International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing's Sarcoma Family of Tumours reecur Temozolomide International Randomised Controlled Trial of Chemotherapy for the Treatment Relapsed/refractory Ewing of Recurrent and Primary Refractory Ewing Sarcoma sarcoma CNS Low Grade Glioma LGG 2 Cooperative Multicentre Study for Children And Adolescents With Low Grade Glioma Intracranial Germ Cell SIOP CNS GCT II, Prospective trial for the diagnosis and treatment of children, adolescents and Tumour young adults with Intracranial Germ Cell Tumour. Ependymoma SIOP Ependymoma II An international clinical program for the diagnosis and treatment of children, adolescents and young adults with ependymoma POSCU Involvement Supportive Care Level 1 G CSF administration? G CSF administration? G CSF administration at Referral to Outside CCN Surgery at Royal Orthopaediac Hospital Birmingham / Closed to Recruitment Closed to Recruitment HODGKINS dular lymphocytepredominant Hodgkin s LEUKAEMIA Acute Lymphoblastic Leukaemia (ALL) and lymphoma EuroNet PHL LP1 Prednisolone EuroNet Paediatric Hodgkin s Group. First international Inter Group Study for nodular lymphocyte predominant Hodgkin s in Children and Adolescents UKALL 2011 Methotrexate, Infant ALL Interfant 06 Methotrexate, Tioguanine, Busulfan, NEUROBLASTOMA United Kingdom National Randomised Trial for Children and Young Adults with Acute Lymphoblastic Leukaemia and 2011 Cytarabine administration Interfant 06 Cytarabine administration High Risk Neuroblastoma HRNBL Isotretinoin High Risk Neuroblastoma Study 1 of SIOP Europe (SIOPEN) G CSF administration Relapsed / Refractory GD2 Isotretinoin Long term continuous infusion ch14.18/cho plus s.c. aldesleukin (IL 2) Neuroblastoma B CELL NHL OR B AL: HIGH Protocol Inter B Prednisolone INTERGROUP TRIAL FOR CHILDREN OR ADOLESCENTS RISK PATIENTS NHL ritux 2010 WITH B CELL NHL OR B AL: EVALUATION OF RITUXIMAB EFFICACY AND SAFETY IN HIGH RISK PATIENTS SOFT TISSUE SARCOMA n Soft Tissue Sarcoma / Malignant Rhabdoid Tumour n Metastatic Metastatic Relapsed / Refractory NRSTS 2005 STS 2006 03 EpSSG NRSTS 2005 A protocol for n Soft Tissue Sarcomas G CSF administration RMS 2005 Cyclophosphamide RMS 2005 A protocol for n Metastatic G CSF administration at STS 2006 04 RMS 2005 Information in RMS 2005 A protocol for n Metastatic. G CSF administration at STS 2006 04 Phase III VIT 0910 Temozolomide International Randomized Phase II Trial of the Combination of Vincristine and Irinotecan with or without Temozolomide (VI or VIT) in Children and Adults with Refractory or Relapsed Closed to recruitment Ratified: vember 2011, Updated August 2012, Updated May 2013,updated May 2014

Clinical Management Protocols Incorporating the Agreed List of Chemotherapy Regimens (continued) n Trial Protocols Diagnosis Regimen Oral Chemo POSCU Involvement Supportive Care Level 1 Referral to Outside CCN Approval Method BONE Relapsed / Refractory Ewings Irinotecan / Temozolomide Temozolomide Approved CDEG Osteosarcoma, localised Guidelines Standard Chemotherapy Osteosarcoma plus mifamurtide mifamurtide Recommendation to Use Closed Euramos Protocol administration Metastatic Osteosarcoma Guidelines Standard Chemotherapy Osteosarcoma CDEG Approved Relapsed Osteosarcoma Ifosfamide & etoposide (as per EURAMOS) GCSF administration CDEG APPROVED CNS Atypical Teratoid Rhabdoid Tumour (ATRT) Guidelines for Management of ATRT advise EURHAB Protocol Guidelines advise EURHAB closed trial Low Grade Glioma LGG 2 Cooperative Multicentre Study for Children And Adolescents With Low Grade Glioma Closed trial High Grade Glioma High Grade Glioma Guidelines Temozolomide Relapsed/refractory High Grade Glioma PCV (Lomustine,Procarbazine and Vincristine Lomustine, Procarbazine Historical approved at chemo group approval Recurrent high grade glioma Carmustine wafers CDEG May 2015. Funding agreed alert pharmacist NWest Hub (helenpotter1@nhs.net). IFR Wales,IOM Infant High Grade Glioma HIT HGG 2013. International cooperative Phase III trial of the HIT HGG study group for the treatment of high grade glioma, diffuse intrinsic pontine glioma, Proposed trial as guidelines. ITC/Intrventricular chemoherapy at consulatnts discretion and gliomatosis cerebri in children and adolescents < 18 years. Trial not open draft. Refractory Low Grade Glioma Bevacizumab and Irinotecan CDEG Approved. Funding via CDF. Welsh patients IFR WHSCC,IOM Refractory Low Grade Glioma vinblastine weekly Historical High Risk Medulloblastoma M1 M4 >3Yrs Use ST Jude s MB03 with risk adapted standard craniospinal RT post surgery Recommendation. and 4 courses of HD cyclophosphamide/cisplatin. High Risk Medulloblastoma M1 M4 >3Yrs POG 9031 Cisplatin Etoposide Recommendation. n Meta Medulloblastoma M0 >3yrs Standard Risk Medulloblastoma Guideline Lomustine Medulloblastoma < 3 yrs M+ OR R+ Headstart II modified. Includes infants with non desmoplastic phenotype on Temozolomide, Etoposide GCSF administration morphology Relapsed Medulloblastoma / PNET guidelines includes treatment detailed in closed trial CNS 2000 01 closed trial Supratentorial PNET <3yrs (including infants with non desmoplastic phenotype on morphology) Headstart II modified Temozolomide, Etoposide GCSF administration CDEG Infant Medulloblastoma Proposed Infant Medulloblastoma based on SIOP YC MB proposal, Paris 2014 Temozolamide CDEG Ratified: vember 2011, Updated August 2012, Updated May 2013,updated May 2014

Recurrent/progressive medulloblastoma MEMMAT metronomic and targeted anti angiogenesis therapy for children with recurrent/progressive medulloblastoma Thalidomide Etoposide Cyclophosphamide CDEG March 2016. t funded require IFR. IFR Wales,IOM Ependymoma < 3 yrs UKCCSG Infant Ependymoma Interim Guidelines Version 1 May 2006 Ependymoma > 3 yrs guidelines (Ependymoma 99) Relapsed Ependymoma Closed trial Phase II Study of Intravenous Etoposide in Patients with Relapsed Ependymoma (CNS 2001 04) Closed trial Recurrent ependymoma Carmustine wafers CDEG May 2015. t funded require IFR. IFR Wales,IOM n metastatic Pineoblastoma > 3YEARS New guidelines n metastatic Pineoblastoma in Children more than 3 years Sep 2013 Choroid Plexus Tumours CNS SIG v 2015. 6 cycles of CarbEV:Carboplatin,Vincristine, Etoposide v 2015,. Palliative brain tumour chemotherapy Oral temozolomide Temozolomide Published Protocol Palliative brain tumour chemotherapy Oral Etoposide Etoposide NAG 8 Historical Protocol High Risk, unresponsive, progressive or relapsed High dose carboplatin and thiotepa +/ etoposide with stem cell rescue malignant brain tumours in patients up to 19 years CDEG Approved July 2012 GERM CELL Extra cranial Germ Cell tumours Interim Guidelines for the Treatment of Extracranial Germ Cell Tumours Resistant Germ cell Oxaliplatin & Gemcitabine HISTIOCYTOSIS HLH HLH 2004 Protocol, Ciclosporin Historical Protocol (Trial Closed) LCH Guidelines Langerhans Cell Histiocytosis Prednisolone Relapsed / Resistant LCH LCH S 2005 Protocol Cladrabine +/ Cytarabine Methotrexate Historical Protocol (Trial Closed) LCH progression HODGKINS Classical Hodgkin`s Treatment based on Stratum 2 of the upcoming trial protocol LCH IV (Vincristine, Prednisolone,cytarabine) EuroNet Paediatric Hodgkin s Group. Recommendations for the Diagnostics and Treatment of children and adolescents with a classical Hodgkin`s during the Interim phase between the end of the EuroNet PHL C1 Study and the start of the EuroNet PHL C2 Study Prednisolone Prednisolone new as per guideline Relapsed / Refractory Hodgkins Brentuximab CDEG Approved. Funding via CDF, Welsh patients IFR (OFF Euronet PHL C1) WHSCC/IOM Classical Hodgkin`s alternative Tx ABVD doses as per MCCN protocol LEUKAEMIA ALL Interim Guidelines for the Treatment of CYA with ALL and LBL cytarabine administration Relapsed ALL An International Collaborative Trial for Relapsed and Refractory Acute Lymphoblastic Leukaemia (ALL) follow standard arm Methotrexate, Tioguanine, Relapsed/Refractory ALL FLA(+/ G) or FLA IDA Historical Relapsed/Refractory ALL Clofarabine with cyclophosphamide, etoposide, Peg aspasaginase and CDEG Approved. Funding via CDF or check WALES/IOM dexamethasone (see closed R3) as a bridge to transplant Relapsed/Refractory T cell ALL Guidelines based on Nectar 2015 : Nelarabine and modified R3 therapy. Nelarabine funded on CDF or Check WALES/IOM Advice Ratified: vember 2011, Updated August 2012, Updated May 2013,updated May 2014

Philadelphia Positive ALL Philadelphia Positive ALL second line Tx Interim Recommendations for Ph+ ALL in Children utilising closed trial EsPhALL Dasatinib. Dosing in accordance with closed trial : A Phase 2 Multi Center, Historically Controlled Study of Dasatinib Added to Standard Chemotherapy in Pediatric Patients with Newly Diagnosed Philadelphia ChromosomePositive Acute Lymphoblastic Leukemia Imatinib, Methotrexate, cytarabine administration UK Guidance Dasatinib cytarabine administration IFR to CDF.Welsh patients IFR WHSCC/IOM Chronic Myeloid Leukaemia Guidelines for the Management of Chronic Myeloid Leukaemia in Children Imatinib UK Childhood Leukaemia Working Party Acute Promyeloctic Leukaemia APL Protocol UK V1 Management Guidelines ATRA, Methotrexate, Mercaptopurine Acute Myeloid Leukaemia or High Risk Myelodysplastic Syndrome Acute Myeloid Leukaemia in Down's Syndrome Treatment Guidelines for AML or High Risk Myelodysplastic Syndrome Jan 2016 ML DS 2007 A Treatment Recommendation for Acute Myeloid Leukaemia of Down syndrome for adoption by the Children s Cancer and Leukaemia Group () and the United Kingdom and Republic Of Ireland Childhood Leukaemia Clinicians Network Leukaemia Subgroup NCRI Children s Cancer and Leukaemia Clinical Studies Group WEBSITE Guideline Chronic Myeloproliferative Disorders Treatment Recommendations for Chronic Myeloproliferative Disorders in Aspirin, Hydroxycarbamide, UK Childhood Leukaemia Working Party Childhood Anegrilide Relapsed AML Relapsed non APL AML 2010 Historical. Daunoxome requires IFR. Relapsed/Refractory AML FLA(+/ G) or FLA IDA Historical Relapsed/Refractory AML Clofarabine with chemotherapy as a bridge to transplant CDEG Approved. Funding via CDF or WHSCC JMML Leukaemias with ABL Translocations in Patients with Imatinib RESISTANCE OR INTOLERANCE APLASTIC ANAEMIA IV cytarabine, ITC (cytarabine, hydrocortisone), progressing Mercaptopurine to AML type treatment and BMT if required. Dasatinib Dasatinib CDEG Approved Relapsed/Refractory ALL. IFR required. Aplastic Anaemia in Childhood Treatment Aplastic Anaemia in Childhood Treatment Recommendations Version 3.1 4th July 2013 LIVER Hepatoblastoma Standard Risk Cisplatin monotherapy arm of the SIOPEL 3 and 6 Hepatoblastoma High Risk Draft Guidance for treating HR HB: eg superplado arm of the SIOPEL 3. SIOPEL Group Consider SIOPEL IV patient > 8 years Metastatic SIOPEL 4 SIOPEL Group. NEUROBLASTOMA Relapsed/Progressive High Risk Neuroblastoma NEUROBLASTOMA SPECIAL INTEREST GROUP Options for the Treatment of Patients with Relapsed/Progressive High Risk Neuroblastoma March 15 Relapsed Neuroblastoma In house metronomic chemotherapy Cis retinoic acid, etoposide, celecoxib, temozolomide, Imatinib solid tumour Ratified: vember 2011, Updated August 2012, Updated May 2013,updated May 2014

Low and Intermediate Risk Neuroblastoma Guidelines Treatment of Patients with Low/Intermediate Risk Neuroblastoma Jan 2015 Burkitt/Burkitt like and B large cell n Hodgkin Interim Guidelines for the Management of Burkitt/Burkitt like and B large cell n Hodgkin Prednisolone T cell and B cell lymphoblastic lymphoma Interim Guidelines for treatment of Children and Young Persons with Acute Prednisolone, dexamethasone, Cytarabine administration co to check with JH IS THIS EuroLB Lymphoblastic Leukaemia and Lymphoblastic mercaptopurine Anaplastic Large Cell Guidelines Recommending ALCL 99 Relapsed Anaplastic Large Cell NHL 2006 01 ALCL Relapse Protocol Closed Trial Lomustine Recommendation RARE TUMOURS (Miscellaneous) Intracranial Meningioma Guidelines for the Management of Intracranial Meningioma Melanotic Neuroectodermal Tumour of Infancy Nasopharyngeal Carcinoma Adrenocortical Tumours (ACT) & Adrenocortical Carcinoma (ACC) Pancreatic Tumours Endocrine Tumours Craniopharyngioma / Adrenocortical Tumours / Differentiated Thyroid Carcinoma / Phaeochromocytoma / MTC / Hyperparathyroidism & Pituitary Tumours (MEN) Kaposiform Haemangioendothelioma & Kasabach Merritt Syndrome RENAL Guidelines for the Management of Melanotic Neuroectodermal Tumour of Infancy Guidelines for the Investigation and Management of Nasopharyngeal Carcinoma Guidelines on the Management of Adrenocortical Tumours ACT and Mitotane Adrenocortical Carcinoma ACT Guidelines for the Investigation and Management of Pancreatic Tumours Guidelines Paediatric Endocrine Tumour Guidelines GCSF administration Guidelines Sirolimus Sirolimus Wilms Tumour SIOP Wilms UK Protocol SIOP Follow Closed Trial Relapsed / Refractory Wilms and Clear Cell Sarcoma of Kidney RETIBLASTOMA Intraoccular Retinoblastoma I Chemotherapy Unilateral Retinoblastoma following primary enucleation SOFT TISSUE SARCOMA Relapsed Refractory Wilms Tumour and CCSK UKW R Protocol Follow Closed Trial Guidelines for the Management of Children with Intraocular Retinoblastoma I Chemotherapy Guidelines for the Management of Children with Advanced unilateral Retinoblastoma following primary enucleation Metastatic Metastatic (RMS) Treatment Recommendations Cyclophosphamide Relapsed Chemotherapy recommendations for relapsed RMS EpSSG Phase II committee EpSSG Phase II committee RELAPSED and REFRACTORY TUMOURS Generic palliative chemotherapy solids and brain tumours Relapsed and Refractory Extra Cranial Solid Tumours Relapsed and Refractory Extra Cranial Solid Tumours and CNS Tumours STEM CELL TRANSPLANT oral etoposide Etoposide Gemcitabine and docetaxel temozolomide and irinotecan +/ Vincristine (VIT) Temozolomide no no Published Protocol Ratified: vember 2011, Updated August 2012, Updated May 2013,updated May 2014