Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (Closed to Accrual 4-22-2011)
Condition: Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Study type: Interventional
Phase: Phase 1

Summary: 
      This pilot clinical trial studies the side effects of pegaspargase when given together with
      combination chemotherapy in treating patients with newly diagnosed high-risk acute
      lymphoblastic leukemia. Pegaspargase may stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop
      the growth of cancer cells, either by killing the cells, by stopping them from dividing, or
      by stopping them from spreading. Giving more than one drug (combination chemotherapy)
      together with pegaspargase may kill more cancer cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To demonstrate that biweekly intravenous (IV) pegaspargase beginning with Consolidation
      and ending with completion of delayed intensification (DI) in combination with hemi-augmented
      BFM therapy (hABFM) is feasible and safe in children with high risk (HR) acute lymphoblastic
      leukemia (ALL).

      OUTLINE: Patients are stratified according to risk assignment (high-risk [HR]-average [day 29
      minimal residual disease (MRD) < 0.01%] vs HR-high [MRD >= 0.01%, presence of central nervous
      system [CNS]3 leukemia, testicular disease, myeloid/mixed lineage leukemia [MLL]
      rearrangement, hypodiploidy, or steroid therapy within the past month]). Patients are
      assigned to 1 of 2 treatment groups.*

      (Note: *Amendment 2 [4-22-2011] requires changes in the regimens. See the changes below,
      after Maintenance therapy.)

      INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine
      sulfate IV on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days
      1-28; daunorubicin hydrochloride IV over 15 minutes on days 1, 8, 15, and 22; methotrexate IT
      on days 8 and 29*; and pegaspargase IV over 1-2 hours on day 4.

      (Note: *Patients with CNS3 disease [white blood cells [(WBC)] >= 5/uL and positive for blasts
      on cytospin] also receive methotrexate IT on days 15 and 22.)

      CONSOLIDATION THERAPY (begins on day 36 of induction therapy):

      GROUP A (HR-AVERAGE): Patients receive cyclophosphamide IV over 1 hour on days 1 and 29;
      cytarabine IV over 15 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39;
      mercaptopurine PO once daily (QD) on days 1-14 and 29-42; vincristine sulfate IV on days 15,
      22, 43, and 50; methotrexate IT on days 1, 8, 15*, and 22*; and pegaspargase IV over 1-2
      hours on days 15 and 43.

      GROUP B (HR-HIGH): Patients receive cyclophosphamide, cytarabine, mercaptopurine, vincristine
      sulfate, and methotrexate as in Group A. Beginning on day 1, patients also receive
      pegaspargase IV over 1-2 hours every 2 weeks. Patients with CNS3 disease undergo cranial
      radiotherapy QD for 10 days and patients with testicular disease undergo testicular
      radiotherapy QD for 12 days, beginning on day 1 of consolidation.

      (Note: *Patients with CNS3 disease [WBC >= 5/uL and positive for blasts on cytospin] do not
      receive methotrexate IT on days 15 and 22.)

      Interim maintenance (IM) therapy (begins on day 57 of consolidation):

      GROUP A: Patients receive vincristine sulfate IV on days 1, 11, 21, 31, and 41; methotrexate
      IV over 10-15 minutes on days 1, 11, 21, 31, and 41; methotrexate IT on days 1 and 31; and
      pegaspargase IV over 1-2 hours on days 2 and 22.

      GROUP B: Patients receive vincristine sulfate and methotrexate as in Group A. Beginning on
      day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks.

      DI therapy (begins on day 57 of IM):

      GROUP A: Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone
      IV or PO BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 15 minutes on days 1,
      8, and 15; cyclophosphamide IV over 1 hour on day 29; cytarabine IV over 15 minutes or SC on
      days 29-32 and 36-39; thioguanine PO on days 29-42; methotrexate IT on days 1, 29, and 36;
      and pegaspargase IV over 1-2 hours on days 4 and 43.

      GROUP B: Patients receive vincristine sulfate, dexamethasone, doxorubicin hydrochloride,
      cyclophosphamide, cytarabine, thioguanine, and methotrexate as in Group A. Beginning on day
      1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks.

      MAINTENANCE THERAPY (MT; begins on day 57 of DI): All patients receive vincristine sulfate IV
      on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO on
      days 1-84; methotrexate IT on day 1; and methotrexate PO BID on days 8, 15, 22, 29*, 36, 43,
      50, 57, 64, 71, and 78.

      In both groups, MT repeats every 12 weeks until total duration of therapy is 2 years from the
      start of IM for female patients and 3 years from the start of IM for male patients. Patients
      in Group B who did not undergo radiotherapy to the brain during consolidation therapy undergo
      prophylactic cranial radiotherapy (CR) daily for 8 days.

      ([Note: *Patients in Group A also receive methotrexate IT on day 29 of courses 1-4 [no oral
      methotrexate]).

      REVISED MT (RMT): The regimen is the same as standard MT, but 2 of the doses of IT
      methotrexate are omitted (day 29 of courses 3 and 4).
    

Intervention name(s): Cyclophosphamide; Cytarabine; Daunorubicin Hydrochloride; Dexamethasone; Doxorubicin Hydrochloride; Laboratory Biomarker Analysis; Mercaptopurine; Methotrexate; Pegaspargase; Prednisone; Prophylactic Cranial Irradiation; Thioguanine; Vincristine Sulfate
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Other; Drug; Drug; Drug; Drug; Radiation; Drug; Drug
Intervention description(s): Given IV; Given IT and IV or SC; Given IV; Given IV; Given IV; Correlative studies; Given PO; Given IT and PO; Given IV; Given IV or PO; Undergo radiation; Given PO; Given IV
Other intervention name(s): (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Dxevo; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin HCl; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; 3H-Purine-6-thiol; 6 MP; 6 Thiohypoxanthine; 6 Thiopurine; 6-Mercaptopurine; 6-Mercaptopurine Monohydrate; 6-MP; 6-Purinethiol; 6-Thiopurine; 6-Thioxopurine; 6H-Purine-6-thione, 1,7-dihydro- (9CI); 7-Mercapto-1,3,4,6-tetrazaindene; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; Purinethol; U-4748; WR-2785; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate; Mexate-AQ; MTX; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; L-Asparaginase with Polyethylene Glycol; Oncaspar; Oncaspar-IV; PEG-Asparaginase; PEG-L-Asparaginase; PEG-L-Asparaginase (Enzon - Kyowa Hakko); PEGLA; Polyethylene Glycol L-Asparaginase; Polyethylene Glycol-L-Asparaginase; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltasone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Orasone; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; PCI; 2-Amino 6MP; 2-Amino-1,7-dihydro-6H-purine-6-thione; 2-Amino-6-mercaptopurine; 2-Amino-6-purinethiol; 2-Aminopurin-6-thiol; 2-Aminopurine-6(1H)-thione; 2-Aminopurine-6-thiol; 2-Aminopurine-6-thiol Hemihydrate; 2-Mercapto-6-aminopurine; 6-Amino-2-mercaptopurine; 6-Mercapto-2-aminopurine; 6-Mercaptoguanine; 6-TG; 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI); BW 5071; Lanvis; Tabloid; Thioguanine Hemihydrate; Thioguanine Hydrate; Tioguanin; Tioguanine; Wellcome U3B; WR-1141; X 27; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate
Intervention MeSH terms: Cytarabine; Dexamethasone; Dexamethasone acetate; Prednisone; Cortisone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Pegaspargase; Thioguanine; BB 1101; 2-Aminopurine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment