Accelerating Drug Development in Pediatric Cancer: A Novel Phase I Study Design of Venetoclax in Relapsed/Refractory Malignancies

References

• Souers AJ , LeversonJD, BoghaertERet al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med.19(2), 202–208 (2013).
   PubMed Web of Science ®Google Scholar
• Davids MS , LetaiA. Targeting the B-cell lymphoma/leukemia 2 family in cancer. J. Clin. Oncol.30(25), 3127–3135 (2012).
   PubMed Web of Science ®Google Scholar
• Mussai FJ , YapC, MitchellC, KearnsP. Challenges of clinical trial design for targeted agents against pediatric leukemias. Front. Oncol.4, 374 (2015).
   PubMed Web of Science ®Google Scholar
• Moreno L , PearsonADJ, PaolettiXet al. Early phase clinical trials of anticancer agents in children and adolescents – an ITCC perspective. Nat. Rev. Clin. Oncol.14(8), 497–507 (2017).
   PubMed Web of Science ®Google Scholar
• Pearson ADJ , HeroldR, RousseauRet al. Implementation of mechanism of action biology-driven early drug development for children with cancer. Eur. J. Cancer62, 124–131 (2016).
   PubMed Web of Science ®Google Scholar
• Konopleva M , PollyeaDA, PotluriJet al. Efficacy and biological correlates of response in a Phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov.6(10), 1106–1117 (2016).
   PubMed Web of Science ®Google Scholar
• Venclexta (venetoclax) [prescribing information]. AbbVie Inc., IL, USA (2016). www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf.
   Google Scholar
• Venclyxto (venetoclax) [summary of product characteristics]. AbbVie Ltd, Maidenhead, UK (2016). www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004106/WC500218800.pdf.
   Google Scholar
• Bogenberger JM , KornblauSM, PierceallWEet al. BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies. Leukemia28(8), 1657–1665 (2014).
   PubMed Web of Science ®Google Scholar
• Pan R , HogdalLJ, BenitoJMet al. Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia. Cancer Discov.4(3), 362–375 (2014).
   PubMed Web of Science ®Google Scholar
• Touzeau C , DoussetC, Le GouillSet al. The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma. Leukemia28(1), 210–212 (2014).
   PubMed Web of Science ®Google Scholar
• Wei A , StricklandSA, RobozGJet al. Phase I/II study of venetoclax with low-dose cytarabine in treatment-naive, elderly patients with acute myeloid leukemia unfit for intensive chemotherapy: 1-year outcomes. Blood130(Suppl. 1), Abstract 890 (2017).
   Google Scholar
• DiNardo CD , PollyeaDA, JonasBAet al. Updated safety and efficacy of venetoclax with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood130(Suppl. 1), Abstract 2628 (2017).
   PubMedGoogle Scholar
• Benito JM , GodfreyL, KojimaKet al. MLL-rearranged acute lymphoblastic leukemias activate BCL-2 through H3K79 methylation and are sensitive to the BCL-2-specific antagonist ABT-199. Cell Rep.13(12), 2715–2727 (2015).
   PubMed Web of Science ®Google Scholar
• Ackler S , OleksijewA, ChenJet al. Clearance of systemic hematologic tumors by venetoclax (Abt-199) and navitoclax. Pharmacol. Res. Perspect.3(5), e00178 (2015).
   PubMedGoogle Scholar
• de Boer J , YeungJ, ElluJet al. The E2A–HLF oncogenic fusion protein acts through Lmo2 and Bcl-2 to immortalize hematopoietic progenitors. Leukemia25(2), 321–330 (2011).
   PubMed Web of Science ®Google Scholar
• Diaz-Flores E , ComeauxEQ, KimKet al. BCL-2, a therapeutic target for high risk hypodiploid B-cell acute lymphoblastic leukemia. Blood128(22), 280 (2016).
   Web of Science ®Google Scholar
• Peirs S , MatthijssensF, GoossensSet al. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood124(25), 3738–3747 (2014).
   PubMed Web of Science ®Google Scholar
• Anderson NM , HarroldI, MansourMRet al. BCL2-specific inhibitor ABT-199 synergizes strongly with cytarabine against the early immature LOUCY cell line but not more differentiated T-ALL cell lines. Leukemia28(5), 1145–1148 (2014).
   PubMed Web of Science ®Google Scholar
• Jones L , CarolH, EvansKet al. A review of new agents evaluated against pediatric acute lymphoblastic leukemia by the Pediatric Preclinical Testing Program. Leukemia30(11), 2133–2141 (2016).
   PubMed Web of Science ®Google Scholar
• Khaw SL , SuryaniS, EvansKet al. Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia. Blood128(10), 1382–1395 (2016).
   PubMed Web of Science ®Google Scholar
• Leverson JD , PhillipsDC, MittenMJet al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci. Transl. Med.7(279), 279ra40 (2015).
   PubMed Web of Science ®Google Scholar
• Bogenberger JM , DelmanD, HansenNet al. Ex vivo activity of BCL-2 family inhibitors ABT-199 and ABT-737 combined with 5-azacytidine in myeloid malignancies. Leuk. Lymphoma56(1), 226–229 (2015).
   PubMed Web of Science ®Google Scholar
• Li L , PongtornpipatP, TiutanTet al. Synergistic induction of apoptosis in high-risk DLBCL by BCL2 inhibition with ABT-199 combined with pharmacologic loss of MCL1. Leukemia29(8), 1702–1712 (2015).
   PubMed Web of Science ®Google Scholar
• Davids MS , RobertsAW, SeymourJFet al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J. Clin. Oncol.35(8), 826–833 (2017).
   PubMed Web of Science ®Google Scholar
• Swinnen LJ , FlowersCR, WangDet al. Venetoclax (VEN), bendamustine (B) and rituximab (R) in patients (pts) with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL): final results of a Phase I study. Hematol. Oncol.35(Suppl. S2), Abstract 79 (2017).
   Google Scholar
• Bate-Eya LT , den HartogIJ, van der PloegIet al. High efficacy of the BCL-2 inhibitor ABT199 (venetoclax) in BCL-2 high-expressing neuroblastoma cell lines and xenografts and rational for combination with MCL-1 inhibition. Oncotarget7(19), 27946–27958 (2016).
   PubMedGoogle Scholar
• Tanos R , KarmaliD, NalluriS, GoldsmithKC. Select Bcl-2 antagonism restores chemotherapy sensitivity in high-risk neuroblastoma. BMC Cancer16, 97 (2016).
   PubMed Web of Science ®Google Scholar
• Lamers F , SchildL, den HartogIJMet al. Targeted BCL-2 inhibition effectively inhibits neuroblastoma tumour growth. Eur. J. Cancer48(16), 3093–3103 (2012).
   PubMed Web of Science ®Google Scholar
• Teh TC , NguyenNY, MoujalledDMet al. Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1. Leukemia32(2), 303–312 (2017).
   PubMed Web of Science ®Google Scholar
• Lin TL , StricklandSA, FiedlerWet al. Phase Ib/II study of venetoclax with low-dose cytarabine in treatment-naive patients aged ≥65 years with acute myelogenous leukemia. J. Clin. Oncol.34(Suppl. 15), Abstract 7007 (2016).
   Web of Science ®Google Scholar
• Potluri J , XuT, HongWJ, MabryMH. Phase III, randomized, double-blind, placebo-controlled study of venetoclax combined with azacitidine versus azacitidine in treatment-naive patients with acute myeloid leukemia. J. Clin. Oncol.35(15 Suppl.), Abstract TPS7069 (2017).
   Google Scholar
• Zinzani PL , ToppMS, YuenSLSet al. Phase II study of venetoclax plus rituximab or randomized ven plus bendamustine+rituximab (BR) versus BR in patients with relapsed/refractory follicular lymphoma: interim data. Blood128(22), Abstract 617 (2016).
   Web of Science ®Google Scholar
• Zelenetz AD , SallesGA, MasonKDet al. Results of a Phase Ib study of venetoclax plus R- or G-CHOP in patients with B-cell non-Hodgkin lymphoma. Blood128(22), Abstract 3032 (2016).
   Google Scholar
• Roberts AW , DavidsMS, PagelJMet al. Targeting BCL-2 with venetoclax in relapsed chronic lymphocytic leukemia. N. Engl. J. Med.374(4), 311–322 (2016).
   PubMed Web of Science ®Google Scholar
• Chiney MS , MenonRM, BuenoOF, TongB, SalemAH. Clinical evaluation of P-glycoprotein inhibition by venetoclax: a drug interaction study with digoxin. Xenobiotica48(9), 904–910 (2018).
   PubMed Web of Science ®Google Scholar
• Agarwal SK , HuB, ChienD, WongSL, SalemAH. Evaluation of rifampin’s transporter inhibitory and CYP3a inductive effects on the pharmacokinetics of venetoclax, a BCL-2 inhibitor: results of a single- and multiple-dose study. J. Clin. Pharmacol.56(11), 1335–1343 (2016).
   PubMed Web of Science ®Google Scholar
• Salem AH , HuB, FreiseKJ, AgarwalSK, SidhuDS, WongSL. Evaluation of the pharmacokinetic interaction between venetoclax, a selective BCL-2 inhibitor, and warfarin in healthy volunteers. Clin. Drug Investig.37(3), 303–309 (2017).
   PubMed Web of Science ®Google Scholar
• Agarwal SK , DiNardoCD, PotluriJet al. Management of venetoclax–posaconazole interaction in acute myeloid leukemia patients: evaluation of dose adjustments. Clin. Ther.39(2), 359–367 (2017).
   PubMed Web of Science ®Google Scholar
• Fischer U , ForsterM, RinaldiAet al. Genomics and drug profiling of fatal TCF3–HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options. Nat. Genet.47(9), 1020–1029 (2015).
   PubMed Web of Science ®Google Scholar
• Frismantas V , DobayMP, RinaldiAet al. Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia. Blood129(11), e26–e37 (2017).
   PubMed Web of Science ®Google Scholar
• O’Hara K , WrightIM, SchneiderJJ, JonesAL, MartinJH. Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future. Br. J. Clin. Pharmacol.80(6), 1281–1288 (2015).
   PubMed Web of Science ®Google Scholar
• Mirrakhimov AE , AliAM, KhanM, BarbaryanA. Tumor lysis syndrome in solid tumors: an up to date review of the literature. Rare Tumors6(2), 5389 (2014).
   PubMedGoogle Scholar
• Liu S , YuanY. Bayesian optimal interval designs for Phase I clinical trials. J. R. Stat. Soc. Ser. C Appl. Stat.64(3), 507–523 (2015).
   Web of Science ®Google Scholar
• Yin G . Clinical trial design: Bayesian and frequentist adaptive methods. John Wiley & Sons, Hoboken, NJ, USA, 173–175 (2012).
   Google Scholar
• Hay AE , RaeC, FraserGAet al. Accrual of adolescents and young adults with cancer to clinical trials. Curr. Oncol.23(2), e81–e85 (2016).
   PubMed Web of Science ®Google Scholar
• National Cancer Institute . Common Terminology Criteria for Adverse Events (CTCAE) v4.0 (2017).http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.
   Google Scholar
• Salem AH , AgarwalSK, DunbarMet al. Effect of low- and high-fat meals on the pharmacokinetics of venetoclax, a selective first-in-class BCL-2 inhibitor. J. Clin. Pharmacol.56(11), 1355–1361 (2016).
   PubMed Web of Science ®Google Scholar
• Salem AH , DunbarM, AgarwalSK. Pharmacokinetics of venetoclax in patients with 17p deletion chronic lymphocytic leukemia. Anticancer Drugs28(8), 911–914 (2017).
   PubMed Web of Science ®Google Scholar
• Cheson BD , FisherRI, BarringtonSFet al. Recommendations for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J. Clin. Oncol.32(27), 3059–3068 (2014).
   PubMed Web of Science ®Google Scholar
• Park JR , BagatellR, CohnSLet al. Revisions to the International Neuroblastoma Response Criteria: a consensus statement from the National Cancer Institute Clinical Trials Planning Meeting. J. Clin. Oncol.35(22), 2580–2587 (2017).
   PubMed Web of Science ®Google Scholar
• Eisenhauer EA , TherasseP, BogaertsJet al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer45(2), 228–247 (2009).
   PubMed Web of Science ®Google Scholar
• Leverson JD , SampathD, SouersAJet al. Found in translation: how preclinical research is guiding the clinical development of the BCL2-selective inhibitor venetoclax. Cancer Discov.7(12), 1376–1393 (2017).
   PubMed Web of Science ®Google Scholar
• Vandenberg CJ , CoryS. ABT-199, a new Bcl-2-specific BH3 mimetic, has in vivo efficacy against aggressive Myc-driven mouse lymphomas without provoking thrombocytopenia. Blood121(12), 2285–2288 (2013).
   PubMed Web of Science ®Google Scholar
• Del Gaizo Moore V , LetaiA. BH3 profiling – measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions. Cancer Lett.332(2), 202–205 (2013).
   PubMed Web of Science ®Google Scholar
• Vassal G , RousseauR, BlancPet al. Creating a unique, multistakeholder Paediatric Oncology Platform to improve drug development for children and adolescents with cancer. Eur. J. Cancer51(2), 218–224 (2015).
   PubMed Web of Science ®Google Scholar
• Seymour JF , MaS, BranderDMet al. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a Phase Ib study. Lancet Oncol.18(2), 230–240 (2017).
   PubMed Web of Science ®Google Scholar