Clinical Trials /

Personalized Kinase Inhibitor Therapy Combined With Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia

NCT02779283

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Personalized Kinase Inhibitor Therapy Combined With Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia
  • Official Title: A Phase Ib Feasibility Study of Personalized Kinase Inhibitor Therapy Combined With Induction in Acute Leukemias Who Exhibit In Vitro Kinase Inhibitor Sensitivity

Clinical Trial IDs

  • ORG STUDY ID: IRB00011766
  • SECONDARY ID: NCI-2016-00083
  • SECONDARY ID: IRB00011766
  • SECONDARY ID: P30CA069533
  • NCT ID: NCT02779283

Conditions

  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Cyclophosphamide(-)-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- 138719Arm II (ALL)
Cytarabine.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-28453Arm I (AML)
DasatinibBMS-354825, SprycelArm I (AML)
DexamethasoneAacidexam, 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, VisumetazoneArm II (ALL)
Doxorubicin Hydrochloride5,12-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, RubexArm II (ALL)
Idarubicin4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDRArm I (AML)
IdelalisibCAL-101, GS 1101, GS-1101, Phosphoinositide-3 Kinase Delta Inhibitor CAL-101, ZydeligArm I (AML)
Leucovorin CalciumAdinepar, 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, WellcovorinArm II (ALL)
MethotrexateAbitrexate, 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-19039Arm II (ALL)
Methylprednisolone Sodium SuccinateA-MethaPred, Asmacortone, Cryosolona, Medrate, Metypred, Prednilem, Solu Moderin, Solu-Medrol, Solu-MedroneArm II (ALL)
Ponatinib HydrochlorideAP24534 HCl, IclusigArm I (AML)
RituximabABP 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, RTXM83Arm II (ALL)
Ruxolitinib PhosphateINCB-18424 Phosphate, JakafiArm I (AML)
Sorafenib TosylateBAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenibArm I (AML)
Sunitinib MalateSU011248, SU11248, sunitinib, SutentArm I (AML)
Vincristine SulfateKyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfateArm II (ALL)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (AML)ExperimentalPatients receive cytarabine IV continuously over 24 hours on days 1-7, and idarubicin IV over 30 minutes on days 1-3.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. Based on the results of the kinase inhibitor assay (In Vitro 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.
  • Cytarabine
  • Dasatinib
  • Idarubicin
  • Idelalisib
  • Ponatinib Hydrochloride
  • Ruxolitinib Phosphate
  • Sorafenib Tosylate
  • Sunitinib Malate
Arm II (ALL)ExperimentalPatients 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. Based on the results of the kinase inhibitor assay (In Vitro 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.
  • Cyclophosphamide
  • Cytarabine
  • Dasatinib
  • Dexamethasone
  • Doxorubicin Hydrochloride
  • Idelalisib
  • Leucovorin Calcium
  • Methotrexate
  • Methylprednisolone Sodium Succinate
  • Ponatinib Hydrochloride
  • Rituximab
  • Ruxolitinib Phosphate
  • Sorafenib Tosylate
  • Sunitinib Malate
  • Vincristine Sulfate

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically confirmed AML or ALL, excluding acute promyelocytic
             leukemia (APL); for histological confirmation, a bone marrow biopsy and aspirate must
             be reviewed at Oregon Health & Science University (OHSU)

          -  Patients must have newly diagnosed AML or ALL without previous treatment; hydroxyurea
             will be allowed to control peripheral blast count as clinically indicated but would
             need to be stopped prior to initiation of tyrosine kinase inhibitor [TKI]); all-trans
             retinoic acid (ATRA) is permitted during the period prior to ruling out a diagnosis of
             APL; previous radiation treatment is allowable; patients must be deemed eligible for
             treatment with cytotoxic induction chemotherapy with cytarabine and idarubicin for AML
             or hyper-cyclophosphamide, dexamethasone, doxorubicin, vincristine sulfate (CVAD) for
             ALL; patients newly diagnosed with ALL must have received no prior treatment for their
             ALL with the exception of steroids (i.e. prednisone, dexamethasone); intrathecal
             methotrexate or cytarabine, allowed prior to and throughout the enrollment period for
             AML and ALL

          -  Subjects must be aged between >= 18 years and =< 64 for AML and > 40 and =< 64 for ALL

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Total bilirubin < 2.0 x institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
             institutional ULN and thought to be due to hepatocellular dysfunction

          -  Potassium > lower limit of normal (LLN) or correctable with supplements prior to first
             dose of study medication

          -  Magnesium > LLN or correctable with supplements prior to first dose of study
             medication

          -  Total calcium (corrected for serum albumin) >= LLN or correctable with supplements
             prior to first dose of study medication

          -  Serum amylase and lipase =< 1.5 x institutional ULN

          -  International normalized ratio (INR) =< 2.0 or correctable to 2.0 with vitamin K
             therapy

          -  Corrected QT (QTc) =< 450 msec. for men or QTc =< 470 msec. for women

          -  Creatinine < 2.0 x ULN

          -  No clinically significant uncontrolled infections as determined by investigator

          -  Patients must be able to take oral medications

          -  Persons of reproductive potential must agree to an adequate method of contraception
             throughout treatment and for at least 4 weeks after study drug is stopped

               -  Women of childbearing potential must have a negative serum or urine pregnancy
                  test within 8 days prior to start of study drug administration

          -  Patients must be willing to accept blood product transfusions

          -  Ability to understand and the willingness to sign a written informed consent document
             and Health Insurance Portability and Accountability Act (HIPAA) documentation

          -  DRUG-SPECIFIC INCLUSION CRITERIA

          -  DASATINIB

               -  Women of childbearing potential (WOCBP) must have a negative serum or urine
                  pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human
                  chorionic gonadotropin [HCG]) within 24 hours prior to the start of study drug

               -  Women must not be breastfeeding

               -  WOCBP must agree to follow instructions for method(s) of contraception for the
                  duration of treatment with study drug, plus 30 days (duration of ovulatory cycle)
                  for a total of 30 days post-treatment completion

               -  Men who are sexually active with WOCBP must agree to follow instructions for
                  method(s) of contraception for the duration of treatment with study drug plus 90
                  days (duration of sperm turnover) for a total of 90 days post-treatment
                  completion

               -  Azoospermic males and WOCBP, who are not heterosexually active, are exempt from
                  contraceptive requirements; however, WOCBP must still undergo pregnancy testing

               -  Investigators shall counsel WOCBP and male subjects who are sexually active with
                  WOCBP on the importance of pregnancy prevention and the implications of
                  unexpected pregnancy; investigators shall advise WOCBP and male subjects who are
                  sexually active with WOCBP on the use of highly effective contraception; highly
                  effective methods of contraception have a failure rate of < 1% when used
                  consistently and correctly

               -  At a minimum, subjects must agree to the use of two methods of contraception,
                  with one method being highly effective and the other method being either highly
                  effective or less effective

        Exclusion Criteria:

          -  Newly diagnosed AML patients who are identified with FLT3-ITD or tyrosine kinase
             domain (TKD) point mutation in the codon for an aspartate (D835) or an isoleucine
             (I836) residue

          -  Patients with a diagnosis of Philadelphia chromosome (Ph)+ ALL are not eligible

          -  Subjects who are currently receiving any other investigational agents

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to study agent or other agents used in the study

          -  Drugs that affect the cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4)
             systems are allowed but should be used with caution depending on specific kinase
             inhibitor used

          -  All outside study medications and supplements will be reviewed and monitored by the
             inpatient pharmacy team; patients will be discouraged from taking herbals and
             additional supplements

          -  Patients should not be prescribed concomitant medications that may contribute to
             prolonged QTc without consultation with the chemotherapy pharmacist; additional ECGs
             should be done at the investigator?s discretion to ensure the subject?s safety; drugs
             that are generally accepted to increase the risk of Torsades de Pointes, include (but
             not limited to):

               -  Quinidine, procainamide, disopyramide

               -  Amiodarone, ibutilide, dofetilide, sotalol

               -  Erythromycin, clarithromycin

               -  Chlorpromazine, mesoridazine, thioridazine, pimozide

               -  Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
                  halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine

          -  Left ventricular ejection fraction < 50%

          -  Uncontrolled intercurrent illness including but not limited to, symptomatic New York
             Heart Association (NYHA) class III congestive heart failure, uncontrolled angina
             pectoris, myocardial infarction or stroke within 6 months prior to enrollment, or
             psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Patients with a known human immunodeficiency virus (HIV) diagnosis are excluded from
             the study

          -  History of hypersensitivity to any of the kinase inhibitors included in this study

          -  Pregnant or lactating women are excluded from the study

          -  Diagnosed congenital long QT syndrome

          -  Any history of significant bleeding disorder unrelated to cancer, including any
             congenital bleeding disorder or any acquired bleeding disorder within one year of
             start of study

          -  Any history of clinically significant ventricular arrhythmia (such as ventricular
             tachycardia, ventricular fibrillation or torsade de pointes)

          -  Patients must not have clinically significant malabsorption syndrome or history

          -  All patients must discontinue anti-platelet agents or anticoagulants 7 days prior to
             initiation of study drug

          -  All patients with unhealed wounds or fistulas should not be given vascular endothelial
             growth factor (VEGF) inhibiting TKIs

          -  DRUG-SPECIFIC EXCLUSION CRITERIA

          -  PONATINIB

               -  Patients with cytogenetically ?favorable risk' AML (core-binding factor
                  leukemias) will not be enrolled on the ponatinib arm; testing with cytogenetics
                  and fluorescence in situ hybridization (FISH) can establish this subtype within 7
                  days of the diagnostic bone marrow biopsy

               -  History of acute pancreatitis within 1 year of study or history of chronic
                  pancreatitis

               -  Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)

               -  Any history of myocardial infarction, stroke, or revascularization

                    -  Any history of venous thromboembolism including deep venous thrombosis or
                       pulmonary embolism with the exception of upper Extremity/Line associated
                       deep vein thrombosis (DVTs) which are adequately treated (line removed
                       and/or patient anti-coagulated)

               -  Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm
                  Hg); patients with hypertension should be under treatment on study entry to
                  effect blood pressure control

          -  DASATINIB

               -  Any history of second or third degree heart block (may be eligible if the subject
                  currently has a pacemaker)

               -  Known pulmonary arterial hypertension

               -  Patients may not have clinically significant pleural or pericardial effusion per
                  provider discretion

          -  SORAFENIB

               -  Major surgery, open biopsy, or significant traumatic injury within 30 days

               -  Non-healing wound, ulcer, or bone fracture

               -  Thrombotic or embolic venous or arterial events, such as cerebrovascular
                  accident, including transient ischemic attacks, arterial thrombosis, deep vein
                  thrombosis and pulmonary embolism within the past 6 months

               -  Upper Extremity/Line associated DVTs which are adequately treated (line removed
                  and/or patient anticoagulated) are eligible

               -  Uncontrolled hypertension

               -  Active bleeding during screening

               -  Hypersensitivity to sorafenib

          -  Idelalisib

               -  Ongoing drug-induced liver injury, chronic active hepatitis C (hepatitis C virus
                  [HCV]), chronic active hepatitis B (hepatitis B virus [HBV]), alcoholic liver
                  disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic
                  obstruction caused by cholelithiasis, cirrhosis of the liver, portal
                  hypertension, or history of autoimmune hepatitis

               -  Ongoing symptomatic pneumonitis

               -  Ongoing inflammatory bowel disease or autoimmune colitis

               -  Ongoing cytomegalovirus (CMV) infection, treatment, or prophylaxis within the
                  past 28 days prior to the screening test for active CMV

               -  History of serious allergic reaction including anaphylaxis and epidermal
                  necrolysis

          -  Ruxolitinib

               -  Chronic active hepatitis C (HCV)
      
Maximum Eligible Age:64 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of subjects who start a targeted drug
Time Frame:On day 8
Safety Issue:
Description:A proportion of subjects whose targeted drug is identified and who start the kinase-inhibitor drug on day 8 will be estimated among all screened subjects along with the 95% confidence interval using the feasibility analysis set.

Secondary Outcome Measures

Measure:Incidence of any grade 3 or higher dose limiting toxicity graded (DLT) according to Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 6 weeks post-treatment
Safety Issue:
Description:DLT events will be tabulated and summarized. The incidence of DLT and its 95% confidence interval will be provided for the entire safety analysis set as well as for each targeted drug separately.
Measure:Overall objective response rates defined as morphologic, cytogenetic and molecular complete response (CR) rates at the end of induction period
Time Frame:At 14 days post-induction treatment
Safety Issue:
Description:The proportion and its 95% confidence interval will be provided for morphologic CR rate, cytogenetic CR rate, and molecular CR rate at the end of induction period. The descriptive statistics (mean, standard deviation, median, minimum and maximum) will be provided for % blasts at day 14 (+/- 3 days) for acute myeloid leukemia or show signs of disease progression requiring alternative treatment (re-induction) during the 21 day targeted treatment period (days 8-28) for acute lymphoblastic leukemia. The proportion and its 95% confidence interval will be provided for the proportion of patients who show sensitivity to each of the study drugs (i.e., IC50 < 20% of median IC50).
Measure:Proportion of patients who show sensitivity to each of the study kinase inhibitors
Time Frame:Baseline
Safety Issue:
Description:Measured as half maximal inhibitory concentration (IC50) < 20% of median IC50.
Measure:Overall survival
Time Frame:From date of the first treatment assessed up to 1 year
Safety Issue:
Description:Kaplan-Meier method will be used to estimate overall survival.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:OHSU Knight Cancer Institute

Last Updated

August 1, 2018