ARM A (3xR-CHOP/3xR-DHAP + ASCT + 2 års vedligehold med observation)

Transkript

1 ARM A (xr-chp/xr-dhap + ASCT + års vedligehold med observation) R-CHP bs. Behandlingen gives skiftevis R-CHP / R-DHAP (R-DHAP se andet skema) SERIE ++ Serie nr. (gives med ugers interval) SERIE SERIE SERIE Behandlingsdag nr: Dags nr. pr. serie DAT: Rituximab mg/m I.V. Cyclofosfamid 0 mg/m i.v. Doxorubicin 0 mg/m i.v. Vincristin.4 mg/m (max.0 mg) T. Prednisolon 00 mg/dag p.o dgl. T. Paracetamol g + T. Clemastin mg eller T. Cetirizin 0 mg T. Allopurinol 00 mg x i dage KVALMEBEHANDLING MM: T. ndansetron efter vægt x T. Motilium 0 mg x dgl. BLDPRØVER: Hæm + diff. Nyre/væske tal () () Lever + koag. Tal () () Medicin status B-symp + PS bjektiv undersøgelse AE registrering 4 P:\FIN\Lukkede Mapper\44\Hjemmesiden\Protokoller og diverse skemaer til hjemmesiden\lymfomer og CLL\Aktive\Triangle\Beh.skema ARM_A_vers_jan0.docx Side af

2 ARM A (xr-chp/xr-dhap + ASCT + års vedligehold med observation) R-DHAP SERIE +4+ Serie nr. (gives med ugers interval) Behandlingsdag nr: 4 Dags nr. pr. serie 4 8 DAT: bs. Behandlingen gives skiftevis R-CHP / R-DHAP (R-CHP, se andet skema) SERIE SERIE 4 SERIE * EI Rituximab mg/m i.v. Cisplatin 00 mg/m kont. i.v. over 4 timer (Start dag kl. 0.00) Ara-C g/m i.v. o t. hver.time (Start dag kl. 0.00) T. Dexametason 40 mg T. Panodil g + T. Cetirizin 0 mg Hydrering start kl dag : Se DHAP (CADD-Pumpe) væskeskema på hj.side T. Furix 40 mg x + P.N. max x (kl og 4.00) T. Kaleorid 0 mg x + P.N. T. Mablet x T. Allopurinol 00 mg x i dage Inj. GCSF KVALMEBEHANDLING: T. Aloxi 00 µg T. Emend mg + 80 mg +80 mg T. Motilium 0 mg x T. lanzapin 0 mg P.N BLDPRØVER: Hæm + diff. Nyre/væske tal Lever + koag. tal HCG, kun fertile kvinder Medicin status* B-symp + PS bjektiv undersøgelse CT skanning (hals, thorax, abd.,pelvis) PET (ikke obligatorisk) Knoglemarvsundersøg else inkl. MRD til afd. 404 EKG (evt. EKK) 8 MUGA Vægt + væskebalance EDTA Clearance Høst /Leukaferese 9 AE registrering 4 Gå til _BEAM skemaet. BEAM DAG 0 (ASCT) SKAL LIGGE 4- UGER EFTER DHAP CD. P:\FIN\Lukkede Mapper\44\Hjemmesiden\Protokoller og diverse skemaer til hjemmesiden\lymfomer og CLL\Aktive\Triangle\Beh.skema ARM_A_vers_jan0.docx Side af

3 ARM A (xr-chp/xr-dhap + ASCT + års vedligehold med observation) *Vigtigt CYD skal startsen fredag iht. høst (der skal startes om mandagen) ) Rituximab iflg. afdelingen procedure. Må gives dag 0 eller dag. ) Kun i safety Run-in fasen, de første 0 patienter der indgår i. ) A complete physical examination should include an evaluation of head, eye, ear, nose, and throat and the cardiovascular, dermatological, musculoskeletal, respiratory, gastrointestinal, and neurological systems. Changes from baseline abnormalities should be recorded at each subsequent physical examination. New or worsened abnormalities should be recorded as adverse events if appropriate. As part of tumor assessment, physical examinations should also include the evaluation of the presence and degree of enlarged lymph nodes, hepatomegaly, and splenomegaly. A targeted physical examination should be limited to systems of primary relevance that is, cardiovascular, respiratory, those associated with symptoms, and those associated with tumor assessment (lymph nodes, liver, and spleen). 4) AE + SAE assessment: From the time of randomization up to 0 days after last visit with the last individual specific examination of the subject. Side I protokollen. ) G-CSF mandatory in R-DHAP from D daily μg/kgkg until recovery of WBC >. G/l. Alternatively pegfilgastrim may be applied once at D. For the regeneration of granulopoiesis and mobilisation of peripheral stem cells G-CSF will be started on day of the third DHAP cycle (treatment cycle ) at a dose of 0 μg/kg body weight and will be continued until the completion of stem cell harvest. Lonquex mg CY+4. Nivestim 0 mikrogram/kg CY. ) BM biopsy mandatory if BM was involved at screening, optional if BM was free of lymphoma at screening, but strongly recommended. For flere detaljer se appendix på side 9 i protokollen. 8) ECG or Echocadiography: If clinically indicated. 9) Høst startes om mandagen. P:\FIN\Lukkede Mapper\44\Hjemmesiden\Protokoller og diverse skemaer til hjemmesiden\lymfomer og CLL\Aktive\Triangle\Beh.skema ARM_A_vers_jan0.docx Side af

4 ARM A+I (xr-chp/xr-dhap + ASCT + år vedligehold R-CHP SERIE ++ bs. Behandlingen gives skiftevis R-CHP / R-DHAP (R-DHAP, se andet skema) Serie nr. (gives med ugers interval) SERIE SERIE SERIE Behandlingsdag nr: Dags nr. pr. serie DAT: Rituximab mg/m I.V. Cyclofosfamid 0 mg/m i.v. Doxorubicin 0 mg/m i.v. Vincristin.4 mg/m (max.0 mg) T. Prednisolon 00 mg/dag p.o dgl. T. Ibrutinib 0 mg dgl dag -9 T. Paracetamol g + T. Clemastin mg eller T. Cetirizin 0 mg T. Allopurinol 00 mg x i dage KVALMEBEHANDLING MM: T. ndansetron efter vægt x T. Motilium 0 mg x dgl. BLDPRØVER: Hæm + diff. Nyre/væske tal () () Lever + koag. tal () () Medicin status 4 B-symp + PS bjektiv undersøgelse AE registrering P:\FIN\Lukkede Mapper\44\Hjemmesiden\Protokoller og diverse skemaer til hjemmesiden\lymfomer og CLL\Aktive\Triangle\Beh.skema ARM_A+I_vers_jan0.docx Side af

5 ARM A+I (xr-chp/xr-dhap + ASCT + år vedligehold R-DHAP SERIE +4+ bs. Behandlingen gives skiftevis R-CHP / R-DHAP (R-CHP, se andet skema) Serie nr. (gives med ugers interval) SERIE SERIE 4 SERIE * Behandlingsdag nr: 4 Dags nr. pr. serie 4 8 DAT: Rituximab mg/m i.v. Cisplatin 00 mg/m kont. i.v. over 4 timer (Start dag kl. 0.00) Ara-C g/m i.v. o t. hver.time (Start dag kl. 0.00) T. Dexametason 40 mg T. Panodil g + T. Cetirizin 0 mg Hydrering start kl dag : Se DHAP (CADD-Pumpe) væskeskema på hj.side T. Furix 40 mg x + P.N. max x (kl og 4.00) + p.n T. Kaleorid 0 mg x + P.N. T. Mablet x T. Allopurinol 00 mg x i dage Inj. GCSF s.c KVALMEBEHANDLING : T. Aloxi 00 µg T. Emend mg + 80 mg +80 mg T. Motilium 0 mg x T. lanzapin 0 mg P.N BLDPRØVER: Hæm + diff. Nyre/væske tal Lever + koag. tal Medicin status 4 B-symp + PS bjektiv undersøgelse CT skanning (hals, thorax, abd,pelvis) PET (ikke obligatorisk) Knoglemarvsundersøg else inkl. MRD til afd EKG (evt. EKK) 9 MUGA Vægt + væskebalance EDTA Clearance Høst /Leukaferese 0 AE registrering Gå til _BEAM skemaet. BEAM DAG 0 (ASCT) SKAL LIGGE 4- UGER EFTER DHAP CD. P:\FIN\Lukkede Mapper\44\Hjemmesiden\Protokoller og diverse skemaer til hjemmesiden\lymfomer og CLL\Aktive\Triangle\Beh.skema ARM_A+I_vers_jan0.docx Side af

6 ARM A+I (xr-chp/xr-dhap + ASCT + år vedligehold *Vigtigt CYD skal startsen fredag iht. høst (der skal startes om mandagen) ) Rituximab iflg. afdelingen procedure. Må gives dag 0 eller dag. ) pbevares og udleveres af KAT (-98) During the study, subjects receiving Ibrutinib should avoid consuming food and beverages containing grapefruit or Seville oranges as these contain certain ingredients that inhibit CYPA4/ enzymes. For flere detaljer se protokol side 4. ) Kun i safety Run-in fasen, de første 0 patienter der indgår i. 4) Ibrutinib is metabolized primarily by CYPA4/ (Section..). Co-administration of ibrutinib with strong CYPA4/ inducers (such as carbamazepine and rifampin) can decrease ibrutinib plasma concentrations and should be avoided. Since no exposure data are available in patients treated concomitantly with strong inhibitors of CYPA4/ (eg, ketoconazole, indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, telithromycin, itraconazole, and nefazadone), these inhibitors should be avoided. If ibrutinib must be administered with a strong inhibitor the national coordinating investigator should be consulted before use, and a dose reduction of ibrutinib to 40 mg daily or a temporary hold of ibrutinib should be considered. Patients should be monitored for signs of ibrutinib toxicity. If the benefit outweighs the risk and a moderate CYPA4/ inhibitor must be used, monitor patient for toxicity and follow dose modification guidance as needed. Avoid grapefruit and Seville oranges during ibrutinib treatment, as these contain moderate inhibitors of CYPA4/. ) A complete physical examination should include an evaluation of head, eye, ear, nose, and throat and the cardiovascular, dermatological, musculoskeletal, respiratory, gastrointestinal, and neurological systems. Changes from baseline abnormalities should be recorded at each subsequent physical examination. New or worsened abnormalities should be recorded as adverse events if appropriate. As part of tumor assessment, physical examinations should also include the evaluation of the presence and degree of enlarged lymph nodes, hepatomegaly, and splenomegaly. A targeted physical examination should be limited to systems of primary relevance that is, cardiovascular, respiratory, those associated with symptoms, and those associated with tumor assessment (lymph nodes, liver, and spleen). ) AE + SAE assessment: From the time of randomization up to 0 days after last visit with the last individual specific examination of the subject. Side I protokollen. ) G-CSF mandatory in R-DHAP from D daily μg/kgkg until recovery of WBC >. G/l. Alternatively pegfilgastrim may be applied once at D. For the regeneration of granulopoiesis and mobilisation of peripheral stem cells G-CSF will be started on day of the third DHAP cycle (treatment cycle ) at a dose of 0 μg/kg body weight and will be continued until the completion of stem cell harvest. Lonquex mg CY+4. Nivestim 0 mikrogram/kg CY. 8) BM biopsy mandatory if BM was involved at screening, optional if BM was free of lymphoma at screening, but strongly recommended. For flere detaljer se appendix på side 9 i protokollen. 9) ECG or Echocadiography: If clinically indicated. 0) Høst starts om mandagen.. P:\FIN\Lukkede Mapper\44\Hjemmesiden\Protokoller og diverse skemaer til hjemmesiden\lymfomer og CLL\Aktive\Triangle\Beh.skema ARM_A+I_vers_jan0.docx Side af

7 ARM I (xr-chp/xr-dhap + års vedligehold R-CHP SERIE ++ bs. Behandlingen gives skiftevis R-CHP / R-DHAP (R-DHAP, se andet skema) Serie nr. (gives med ugers interval) SERIE SERIE SERIE Behandlingsdag nr: Dags nr. pr. serie DAT: Rituximab mg/m I.V. Cyclofosfamid 0 mg/m i.v. Doxorubicin 0 mg/m i.v. Vincristin.4 mg/m (max.0 mg) T. Prednisolon 00 mg/dag p.o dgl. T. Ibrutinib 0 mg dgl dag -9 T. Paracetamol g + T. Cetirizin 0 mg KVALMEBEHANDLING T. ndansetron efter vægt x T. Motilium 0 mg x dgl. BLDPRØVER: Hæm + diff. Nyre/væske tal () () Lever + koag. Tal () () Medicin status 4 B-symp + PS bjektiv undersøgelse AE registrering P:\FIN\Lukkede Mapper\44\Hjemmesiden\Protokoller og diverse skemaer til hjemmesiden\lymfomer og CLL\Aktive\Triangle\Beh.skema ARM_I_vers_jan0.docx Side af

8 ARM I (xr-chp/xr-dhap + års vedligehold R-DHAP SERIE +4+ Serie nr. (gives med ugers interval) Behandlingsdag nr: 4 Dags nr. pr. serie 4 8 DAT: bs. Behandlingen gives skiftevis R-CHP / R-DHAP (R-CHP, se andet skema) SERIE SERIE 4 SERIE * EI Rituximab mg/m i.v. Cisplatin 00 mg/m kont. i.v. over 4 timer (Start dag kl. 0.00) Ara-C g/m i.v. o t. hver.time (Start dag kl. 0.00) T. Dexametason 40 mg T. Panodil g + T. Cetirizin 0 mg Hydrering start kl dag : Se DHAP (CADD-Pumpe) væskeskema på hj.side T. Furix 40 mg x + P.N. max x (kl og 4.00) T. Kaleorid 0 mg x + P.N. T. Mablet x T. Allopurinol 00 mg x i dage Inj. GCSF s.c KVALMEBEHANDLING: T. Aloxi 00 µg T. Emend mg + 80 mg +80 mg T. Motilium 0 mg x T. lanzapin 0 mg P.N BLDPRØVER: Hæm + diff. Nyre/væske tal Lever + koag. Tal Medicin status 4 B-symp + PS bjektiv undersøgelse CT skanning (hals, thorax, abd.,pelvis) PET (ikke obligatorisk) Knoglemarvsundersøg else inkl. MRD til afd EKG (evt. EKK) 9 MUGA Vægt + væskebalance EDTA Clearance Høst /Leukaferese 0 AE registrering ET besøg svarer til vedligeholdelsesskema måned 0. Gå videre til vedligeholdelsesskema. P:\FIN\Lukkede Mapper\44\Hjemmesiden\Protokoller og diverse skemaer til hjemmesiden\lymfomer og CLL\Aktive\Triangle\Beh.skema ARM_I_vers_jan0.docx Side af

9 ARM I (xr-chp/xr-dhap + års vedligehold *Vigtigt CYD skal startsen fredag iht. høst (der skal startes om mandagen) ) Rituximab iflg. afdelingen procedure. Må gives dag 0 eller dag. ) pbevares og udleveres af KAT (-98) During the study, subjects receiving Ibrutinib should avoid consuming food and beverages containing grapefruit or Seville oranges as these contain certain ingredients that inhibit CYPA4/ enzymes. For flere detaljer se protokol side 4. ) Kun i safety Run-in fasen, de første 0 patienter der indgår i. 4) Ibrutinib is metabolized primarily by CYPA4/ (Section..). Co-administration of ibrutinib with strong CYPA4/ inducers (such as carbamazepine and rifampin) can decrease ibrutinib plasma concentrations and should be avoided. Since no exposure data are available in patients treated concomitantly with strong inhibitors of CYPA4/ (eg, ketoconazole, indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, telithromycin, itraconazole, and nefazadone), these inhibitors should be avoided. If ibrutinib must be administered with a strong inhibitor the national coordinating investigator should be consulted before use, and a dose reduction of ibrutinib to 40 mg daily or a temporary hold of ibrutinib should be considered. Patients should be monitored for signs of ibrutinib toxicity. If the benefit outweighs the risk and a moderate CYPA4/ inhibitor must be used, monitor patient for toxicity and follow dose modification guidance as needed. Avoid grapefruit and Seville oranges during ibrutinib treatment, as these contain moderate inhibitors of CYPA4/. ) A complete physical examination should include an evaluation of head, eye, ear, nose, and throat and the cardiovascular, dermatological, musculoskeletal, respiratory, gastrointestinal, and neurological systems. Changes from baseline abnormalities should be recorded at each subsequent physical examination. New or worsened abnormalities should be recorded as adverse events if appropriate. As part of tumor assessment, physical examinations should also include the evaluation of the presence and degree of enlarged lymph nodes, hepatomegaly, and splenomegaly. A targeted physical examination should be limited to systems of primary relevance that is, cardiovascular, respiratory, those associated with symptoms, and those associated with tumor assessment (lymph nodes, liver, and spleen). ) AE + SAE assessment: From the time of randomization up to 0 days after last visit with the last individual specific examination of the subject. Side I protokollen. ) G-CSF mandatory in R-DHAP from D daily μg/kgkg until recovery of WBC >. G/l. Alternatively pegfilgastrim may be applied once at D. For the regeneration of granulopoiesis and mobilisation of peripheral stem cells G-CSF will be started on day of the third DHAP cycle (treatment cycle ) at a dose of 0 μg/kg body weight (and will be continued until the completion of stem cell harvest. 8) BM biopsy mandatory if BM was involved at screening, optional if BM was free of lymphoma at screening, but strongly recommended. For flere detaljer se appendix på side 9 i protokollen. 9) ECG or Echocadiography: If clinically indicated 0) Patienten skal høstes selvom ASCT ikke indgår i ARM I. P:\FIN\Lukkede Mapper\44\Hjemmesiden\Protokoller og diverse skemaer til hjemmesiden\lymfomer og CLL\Aktive\Triangle\Beh.skema ARM_I_vers_jan0.docx Side af