Protocol AML 03-08

The Thai Pediatric Oncology Group Study Protocol National Protocol for Acute Non-Lymphoblastic Leukemia Protocol name Protocol TPOG-AML-03-08 Protocol for Acute nonlymphoblastic leukemia Modified from Protocol AML-BFM 98: J Clin Oncol 2006: 24: 4499-4516 Open Date 20 May 2008 Patients eligibility 􀂉 Acute nonlymphoblastic leukemia Exclusion criteria 􀂉 Relapsed ANLL Patient’s name Age Sex HN BW Ht BSA Phase I INDUCTION (8 days) Date start //day 1 2 3 4 5 6 7 8 Date given Alkalinization + prophylactic medication + sterile bowel Cytosine Arabinoside _____ mg IV infusion in 24 hr Cytosine Arabinoside _____ mg IV q 12 hr 􀂿􀂿 􀂿􀂿 􀂿􀂿 􀂿􀂿 􀂿􀂿 Idarubicin ___ ___ mg IV Δ Δ Δ Etoposide _______ mg IV drip in I hr 􀂋 􀂋 􀂋 MTX____ _ mg* IT T# BMA aspiration at Day 21 ____/____/____ results : ____________________________________________________ #CNS disease – MTX IT at week 1; then followed by Ara-C IT weekly until CSF -ve Drug Dosage Day Cytosine Arabinoside 100 mg/m2 /day IV infusion in 24 hr 1, 2 Cytosine Arabinoside 50 mg/m2/dose IV q 12 hr x 10 doses 3, 4, 5, 6, 7 Idarubicin 8-12 mg/m2 IV drip in 4 hr 3, 4, 5 Etoposide 100 mg /m2 IV drip in 1 hr 6, 7, 8 Methotrexate IT age adjusted dose intrathecal 1 Prophylactic drugs & Sterile Bowel 􀂃 Sodamint 1 tab PO BID (<5yr) or TID (>5yr) First 2 weeks 􀂃 Zyloric (100 mg) 10 mg/kg/day divided BID-QID First 2 weeks 􀂃 Clotrimazole troche (10 mg) or nystatin suspension 1 tab PO TID (>5yr) or nystatin 2 ml PO QID (<5yr) 1-28 BMA at Day 21 of protocol -If blast > 5% : proceed to phase I-2 (induction 2) regardless of ANC -If blast < 5% : continue phase II (consolidation 1) when WBC >2000 and ANC > 500 -If blast can not evaluate : wait until WBC >2000, then repeat BMA to evaluate remission statusThe Thai Pediatric Oncology Group Study Protocol Patient’s name Age Sex HN BW Ht BSA Phase I-2 INDUCTION 2 (HAM) (5 days) Date start //_ [For patient who failed induction only (Blast >5% from BMA Day 21)] • Start at day 21 of Phase I day 1 2 3 4 5 Date given Alkalinization + prophylactic medication + sterile bowel Cytosine Arabinoside _____ mg IV drip in 3 hr q 12 hr 􀂿􀂿 􀂿􀂿 􀂿􀂿 Mitoxantrone ________ mg IV drip in 30 min 􀂋 􀂋 Decadron eye drops q 4 hr BMA aspiration at Day 21 ____/____/____ results : ____________________________________________________ Drug Dosage Day Cytosine Arabinoside 3 gm/m2 /dose IV drip in 3 hr q 12 hr 1, 2, 3 Mitoxantrone 8-10 mg/m2/dose IV drip in 3 hr 4, 5 Decadron eye drops apply to both eyes before, during and 1 day after Ara-C infusion Prophylactic drugs & Sterile Bowel 􀂃 Sodamint 1 tab PO BID (<5yr) or TID (>5yr) First 2 weeks 􀂃 Zyloric (100 mg) 10 mg/kg/day divided BID-QID First 2 weeks 􀂃 Clotrimazole troche (10 mg) or nystatin suspension 1 tab PO TID (>5yr) or nystatin 2 ml PO QID (<5yr) 1-28 The Thai Pediatric Oncology Group Study Protocol Patient’s name Age Sex HN BW Ht BSA Phase II CONSOLIDATION 1 (AI) (6 days) Date start //• Start at Day 21 of previous phase • Keep WBC > 2000 /mm3 and ANC > 500 /mm3 before start chemotherapy day 1 2 3 4 5 6 Date given Cytosine Arabinoside _____ mg IV infusion in 24 hr Idarubicin ___ ___ mg IV Δ Δ Ara-C____ _ mg* IT T T Drug Dosage Day Cytosine Arabinoside 500 mg/m2 /day IV infusion in 24 hr 1, 2, 3, 4 Idarubicin 7 mg/m2 IV 3, 5 Ara-C intrathecal Age-adjusted dose 0, 6 Co-trimoxazole 5 mg/kg/day divided BID Fri-Sat-Sun Drug <1 yr 1-2 yr 2-3 yr >3 yr Methotrexate 6 8 10 12 * age adjusted dose intrathecal chemotherapy Ara-C 15 20 30 50 The Thai Pediatric Oncology Group Study Protocol Patient’s name Age Sex HN BW Ht BSA Phase III CONSOLIDATION 2 (hAM) (15 days) Date start //• Start at Day 21 of previous phase • Keep WBC > 2000 /mm3 and ANC > 500 /mm3 before start chemotherapy day 1 2 3 4 5 6 7-14 15 Date given Cytosine Arabinoside ___ mg IV drip in 2 hr q 12 hr 􀂿􀂿 􀂿􀂿 􀂿􀂿 Mitoxantrone* ________ mg IV drip in 30 min 􀂋 􀂋 Decadron eye drops q 4 hr Ara-C ______ mg IT T T Drug Dosage Day Cytosine Arabinoside 1 gm/m2 IV drip in 2 hr q 12 hr 1, 2, 3 Mitoxantrone* 8-10 mg/m2/dose IV drip in 3 hr 4, 5 Decadron eye drops apply to both eyes at before, during and 1 day after Ara-C infusion Ara-C intrathecal Age-adjusted dose* 6, 15 Co-trimoxazole 5 mg/kg/day divided BID Fri-Sat-Sun *Mitoxantrone can be omitted, if there is evidence of grade IV myelotoxicity and/or serious infection from the previous phase Drug <1 yr 1-2 yr 2-3 yr >3 yr Methotrexate 6 8 10 12 * age adjusted dose intrathecal chemotherapy Ara-C 15 20 30 50 The Thai Pediatric Oncology Group Study Protocol Patient’s name Age Sex HN BW Ht BSA Phase IV INTENSIFICATION (HAE) (5 days) Date start //_ (This phase can be omitted, if there is evidence of grade IV myelotoxicity or serious infection in the previous phase) • Start at Day 21 of previous phase • Keep WBC > 2000 /mm3 and ANC > 1000 /mm3 before start chemotherapy day 1 2 3 4 5 Date given Cytosine Arabinoside _____ mg IV drip in 3 hr q 12 hr 􀂿􀂿 􀂿􀂿 􀂿􀂿 Etoposide _______ mg IV drip in I hr 􀂋 􀂋 􀂋 􀂋 Decadron eye drops q 4 hr Drug Dosage Day Cytosine Arabinoside 3 gm/m2 /dose IV drip in 3 hr q 12 hr 1, 2, 3 Etoposide 125 mg /m2 IV drip in 1 hr 2, 3, 4, 5 Decadron eye drops apply to both eyes at before, during and 1 day after Ara-C infusion Cotrimoxazole 5 mg/kg/day divided BID Fri-Sat-Sun Phase V CNS PROPHYLAXIS ** 4 weeks Date start //**Only for Patients with initial CNS involvement and age > 2 years only Week 1 2 3 4 Date 6-TG ___________________ (60 mg/m2 day PO) Cranial Irradiation _______ cGy x 10 fractions MTX ___________ mg IT x 4 times T T T T Date given CSF examination: Gross appearance Pandy /Nonne ////Benedict test Cells (RBC /WBC) ////Day 1-14The Thai Pediatric Oncology Group Study Protocol Patient’s name Age Sex HN BW Ht BSA Phase VI MAINTENANCE PHASE (Total duration 12 months) Date Start ____/____/___ Give the following courses q 4 weeks Drug Dose Day Cytosine Arabinoside 40 mg/m2 /day SC or IV x 4 days _________________ Day 1-4 6-Thioguanine 40 mg/m2 /day PO _________________ Daily Co-trimoxazole 5 mg/kg/day divided BID _________________ Fri-Sat-Sun LP + Ara-C IT Age adjusted dose _________________ Day 1 of month 1, 2, 3, 4 BM aspiration (Optional for individual institute) q 6 months Month 1 2 3 4 Date given Chemotherapy 􀃀 􀃀 􀃀 􀃀 BMA, blood chem. 􀂄 LP+ Ara C____ mg IT 􀂋 􀂋 􀂋 􀂋 Month 5 6 7 8 Date given Chemotherapy 􀃀 􀃀 􀃀 􀃀 BMA, blood chem. 􀂄 Month 9 10 11 12 Date given Chemotherapy 􀃀 􀃀 􀃀 􀃀 BMA, blood chem. 􀂄 Drug <1 yr 1-2 yr 2-3 yr >3 yr Methotrexate 6 8 10 12 * age adjusted dose intrathecal chemotherapy Ara-C 15 20 30 50 The Thai Pediatric Oncology Group Study Protocol Phase VII STOP THERAPY after finished maintenance phase ____/____/___ POST TREATMENT GUIDELINES Guidelines for follow up patients post treatment 1. 1st year : 􀂃 PE, CBC q 2 months. 2. 2nd year : 􀂃 PE, CBC q 3 months. 3. 3rd year : 􀂃 PE, CBC q 6 months 4. After 3rd year : 􀂃 PE, CBC q 12 months Bone marrow aspiration 1. Before discontinue chemotherapy 2. Unexplained cytopenia 3. Sign & symptom of relapse Guideline for bactrim prophylaxis 1. Start when consolidation 2. Bactrim is given 5 mg of TMP /kg/day divided bid 2-3 times per week (M-W-F, Fri-Sat-Sun, or Sat-Sun) 3. Stop bactrim prophylaxis 1 week before and during CNS prophylaxis with high-dose methotrexate Reimmunization -post off treatment 1 yr. Evaluation for long term side effects yearly 1. Growth chart 2. Learning problems 3. Endocrine evaluation and consultant when enter adolescent 4. Secondary malignancy