Personalized Kinase Inhibitor Therapy Combined With Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia
Condition: Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase IB trial studies the feasibility of using a functional laboratory based study to
      determine how well the test can be used to select personalized kinase inhibitor therapy in
      combination with standard chemotherapy in treating patients with newly diagnosed acute
      myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It also evaluates safety and
      potential efficacy. Kinase inhibitor is a type of substance that blocks an enzyme called a
      kinase. Human cells have many different kinase enzymes, and they help control important cell
      functions. Certain kinases are more active in some types of cancer cells and blocking them
      may help keep the cancer cells from growing. Testing samples of blood from patients with AML
      and ALL in the laboratory with kinase inhibitors may help determine which kinase inhibitor
      has more activity against cancer cells and which one should be combined with standard of care
      chemotherapy. 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 a personalized kinase inhibitor therapy combined with standard chemotherapy
      may be a better treatment for AML and ALL.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. Determine feasibility of using an in vitro small molecule inhibitor screen to select
      kinase inhibitors to add to standard chemotherapy induction in AML or ALL.

      SECONDARY OBJECTIVES:

      I. Determine the safety and tolerability of the addition of the kinase inhibitors when added
      to standard chemotherapy induction.

      II. Evaluate overall objective response rates at completion of induction therapy.

      III. Evaluate need for re-induction at day 14 (+/- 3 days) for AML. IV. Evaluate sensitivity
      to kinase inhibitors using our in vitro small molecule inhibitor screen in newly diagnosed
      AML/ALL.

      V. Determine twelve-month overall survival.

      TERTIARY OBJECTIVES:

      I. Perform next-generation mutational analysis in primary leukemia samples from study
      subjects at baseline to establish a panel of known mutations for each subject and at the time
      of bone marrow recovery after induction chemotherapy to measure residual disease and evaluate
      utility of next-generation sequencing as a method compared to flow cytometry for minimal
      residual disease (MRD).

      II. Evaluate pharmacokinetics for each individual kinase inhibitor. III. Determine if there
      is a cytogenetic or other risk group that has a higher rate of treatment failure or inability
      to obtain results from the small molecule inhibitor screen.

      OUTLINE: Patients are assigned to 1 of 2 arms.

      ARM I (AML): Patients receive cytarabine intravenously (IV) continuously over 24 hours on
      days 1-7, and idarubicin IV over 30 minutes on days 1-3.

      ARM II (ALL) CYCLE A: Patients receive cyclophosphamide IV over 3 hours twice daily (BID) on
      days 1-3, vincristine sulfate IV on days 4 and 11, doxorubicin hydrochloride IV on day 4,
      dexamethasone PO on days 1-4 and 11-14, and rituximab IV on day 1 and 11 (day 11 only of
      course 1). Treatment repeats every 28 days for up to 4 courses in the absence of disease
      progression or unacceptable toxicity.

      ARM II (ALL) CYCLE B: Patients receive cytarabine IV over 2 hours BID on days 2-3,
      methotrexate IV over 2-22 hours on day 1, methylprednisolone sodium succinate IV BID on days
      1-3, leucovorin calcium IV every 6 hours until methotrexate level is < 0.05 uM and rituximab
      IV on days 1 and 8. Treatment repeats every 28 days for up to 4 courses in the absence of
      disease progression or unacceptable toxicity.

      In all arms, based on the results of the kinase inhibitor assay, patients receive either
      sorafenib tosylate PO BID, sunitinib malate PO daily, dasatinib PO daily, ponatinib
      hydrochloride PO daily, ruxolitinib phosphate or idelalisib PO BID on days 8-28 in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 4-6 weeks, and then for a
      minimum of 1 year.
    

Intervention name(s): Cyclophosphamide; Cytarabine; Dasatinib; Dexamethasone; Doxorubicin Hydrochloride; Idarubicin; Idelalisib; In Vitro Kinase Inhibitor Assay; Leucovorin Calcium; Methotrexate; Methylprednisolone Sodium Succinate; Ponatinib Hydrochloride; Rituximab; Ruxolitinib Phosphate; Sorafenib Tosylate; Sunitinib Malate; Vincristine Sulfate
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Device; Drug; Drug; Drug; Drug; Biological; Drug; Drug; Drug; Drug
Intervention description(s): Given IV; Given IV; Given PO; Given PO; Given IV; Given IV; Given PO; Correlative studies; Given IV; Given IV; Given IV; Given PO; Given IV; Given PO; Given PO; 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; 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; BMS-354825; Sprycel; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron; 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; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; Visumetazone; 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; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; 4-Demethoxydaunomycin; 4-demethoxydaunorubicin; 4-DMDR; CAL-101; GS 1101; GS-1101; Phosphoinositide-3 Kinase Delta Inhibitor CAL-101; Zydelig; Laboratory Biomarker Analysis; Adinepar; Calcifolin; Calcium (6S)-Folinate; Calcium Folinate; Calcium Leucovorin; Calfolex; Calinat; Cehafolin; Citofolin; Citrec; citrovorum factor; Cromatonbic Folinico; Dalisol; Disintox; Divical; Ecofol; Emovis; Factor, Citrovorum; Flynoken A; Folaren; Folaxin; FOLI-cell; Foliben; Folidan; Folidar; Folinac; Folinate Calcium; folinic acid; Folinic Acid Calcium Salt Pentahydrate; Folinoral; Folinvit; Foliplus; Folix; Imo; Lederfolat; Lederfolin; Leucosar; leucovorin; Rescufolin; Rescuvolin; Tonofolin; Wellcovorin; 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; A-MethaPred; Asmacortone; Cryosolona; Medrate; Metypred; Prednilem; Solu Moderin; Solu-Medrol; Solu-Medrone; AP24534 HCl; Iclusig; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; MabThera; Monoclonal Antibody IDEC-C2B8; PF-05280586; Rituxan; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; RTXM83; INCB-18424 Phosphate; Jakafi; BAY 43-9006 Tosylate; BAY 54-9085; Nexavar; sorafenib; SU011248; SU11248; sunitinib; Sutent; Kyocristine; Leurocristine sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Cytarabine; Dexamethasone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Dexamethasone acetate; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Sorafenib; Sunitinib; Dasatinib; Idarubicin; Ponatinib; Idelalisib; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Prednisolone hemisuccinate; Prednisolone phosphate; BB 1101; Calcium; Levoleucovorin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment