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

NCT02779283 | Completed Phase 1 DMC FDA Drug FDA Device

• 3 other identifiers: IRB00011766NCI-2016-00083P30CA069533
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects who start a targeted drug

  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.

  On day 8

Secondary Outcomes (4)

• Incidence of any grade 3 or higher dose limiting toxicity graded (DLT) according to Common Terminology Criteria for Adverse Events version 4.0

  Up to 6 weeks post-treatment

• Overall objective response rates defined as morphologic, cytogenetic and molecular complete response (CR) rates at the end of induction period

  At 14 days post-induction treatment

• Proportion of patients who show sensitivity to each of the study kinase inhibitors

  Baseline

• Overall survival

  From date of the first treatment assessed up to 1 year

Study Arms (2)

Arm I (AML)

EXPERIMENTAL

Patients 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.

Drug: Cytarabine; Drug: Dasatinib; Drug: Idarubicin; Drug: Idelalisib; Device: In Vitro Kinase Inhibitor Assay; Drug: Ponatinib Hydrochloride; Drug: Ruxolitinib Phosphate; Drug: Sorafenib Tosylate; Drug: Sunitinib Malate

Arm II (ALL)

EXPERIMENTAL

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. 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.

Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dasatinib; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Drug: Idelalisib; Device: In Vitro Kinase Inhibitor Assay; Drug: Leucovorin Calcium; Drug: Methotrexate; Drug: Methylprednisolone Sodium Succinate; Drug: Ponatinib Hydrochloride; Biological: Rituximab; Drug: Ruxolitinib Phosphate; Drug: Sorafenib Tosylate; Drug: Sunitinib Malate; Drug: Vincristine Sulfate

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Arm II (ALL)

Cytarabine DRUG

Given IV

Also known as: .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

Arm I (AML); Arm II (ALL)

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Sprycel

Arm I (AML); Arm II (ALL)

Dexamethasone DRUG

Given PO

Also known as: 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

Arm II (ALL)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 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

Arm II (ALL)

Idarubicin DRUG

Given IV

Also known as: 4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR

Arm I (AML)

Idelalisib DRUG

Given PO

Also known as: CAL-101, GS 1101, GS-1101, Phosphoinositide-3 Kinase Delta Inhibitor CAL-101, Zydelig

Arm I (AML); Arm II (ALL)

In Vitro Kinase Inhibitor Assay DEVICE

Correlative studies

Also known as: Laboratory Biomarker Analysis

Arm I (AML); Arm II (ALL)

Leucovorin Calcium DRUG

Given IV

Also known as: 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

Arm II (ALL)

Methotrexate DRUG

Given IV

Also known as: 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

Arm II (ALL)

Methylprednisolone Sodium Succinate DRUG

Given IV

Also known as: A-MethaPred, Asmacortone, Cryosolona, Medrate, Metypred, Prednilem, Solu Moderin, Solu-Medrol, Solu-Medrone

Arm II (ALL)

Ponatinib Hydrochloride DRUG

Given PO

Also known as: AP24534 HCl, Iclusig

Arm I (AML); Arm II (ALL)

Rituximab BIOLOGICAL

Given IV

Also known as: 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

Arm II (ALL)

Ruxolitinib Phosphate DRUG

Given PO

Also known as: INCB-18424 Phosphate, Jakafi

Arm I (AML); Arm II (ALL)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Arm I (AML); Arm II (ALL)

Sunitinib Malate DRUG

Given PO

Also known as: SU011248, SU11248, sunitinib, Sutent

Arm I (AML); Arm II (ALL)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Arm II (ALL)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

Cyclophosphamide; Cytarabine; Dasatinib; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Doxorubicin; Idarubicin; idelalisib; Leucovorin; Methotrexate; merphos; Methylprednisolone Hemisuccinate; Methylprednisolone; ponatinib; Rituximab; CT-P10; ruxolitinib; Sorafenib; Sunitinib; Vincristine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Thiazoles; Sulfur Compounds; Azoles; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Aminopterin; Prednisolone; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phenylurea Compounds; Urea; Amides; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Pyrroles; Indoles; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indolizidines; Indolizines

Study Officials

• Stephen Spurgeon

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 18, 2016
• First Posted: May 20, 2016
• Study Start: January 13, 2016
• Primary Completion: April 19, 2018
• Study Completion: September 20, 2018
• Last Updated: May 26, 2020

Record last verified: 2020-02

Locations

US (1)