Hematologic Malignancies - Siteman Cancer Center

Hematologic MalignanciesLeukemia, Lymphoma, Myelomaand Stem Cell TransplantationFor patients with refractory DLBCL, we are evaluating the drug YM155 in aPhase II multi-institution trial. YM155 is a survivin inhibitor which demonstratedactivity in the Phase I setting and was well-tolerated. Patients with relapsed/refractory DLBCL, and who are not candidates for SCT, are also eligible forSGN-40 in combination with rituximab and gemcitabine. The combinationof rituximab and gemcitabine has demonstrated clinical efficacy and goodtolerability. Toxicity from SGN-40 appears to be most associated with the firstinfusion. The addition of SGN-40 may increase efficacy without significantoverlapping toxicity.Follicular LymphomaMost patients with low-grade lymphomas eventually relapse. In the era priorto rituximab, the average survival was 7 years. While the survival is improving,research is being directed to augment the activity of rituximab. One suchapproach is a Phase II randomized CALGB study, in which we will be evaluatinglenalidomide vs. lenalidomide plus rituximab for patients with relapsedfollicular lymphoma (FL) following a rituximab containing regimen. Patientsmust not be refractory to rituximab. Similarly, in patients who have progressedfollowing previous rituximab therapy, we are also evaluating a Phase IIrandomized, double-blind, placebo-controlled study of Apomab administeredin combination with rituximab. All patients will receive rituximab 375 mg/m2weekly for eight doses with or without 6 cycles of Apomab administered every 3weeks. Apomab is a fully humanized monoclonal antibody that induces apoptosisby engaging death receptors on cancer cells, specifically via the Apo2 ligand/TNFrelatedapoptosis-inducing ligand (Apo2L/TRAIL) death receptor. Our thirdtrial aimed at improving upon rituximab, is a Phase II study of bendamustinein combination with bortezomib and rituximab. Eligible patients must havepreviously received 4 or more doses of rituximab.T-cell lymphomaAlk-1 negative anaplastic large cell lymphoma (ALCL) has a poor prognosis,with most patients relapsing after primary therapy. The anti-CD30 antibody,SGN-30 showed activity in relapsed ALCL (RR 25-30%) and these patientsare now included in the ongoing SGN-35/gemcitabine trial as described aboveunder relapsed HL. Praletrexate, an anti-folate and methotrexate analog hasdemonstrated significant activity against relapsed and refractory aggressive T-celllymphomas (RR 30%). We are currently participating in a multi-center Phase I/IItrial of Praletrexate plus gemcitabine.Relapsed Lymphoma- All HistologiesWe are participating in a multi-center Phase I/II dose-escalation study of PCI-24781, an oral pan-HDAC inhibitor. In pre-clincial studies PCI-24781 hadmore activity than vorinostat, an HDAC inhibitor approved for cutaneous T-celllymphoma. Previously treated patients with most subtypes of lymphoma will beeligible for enrollment.Patients with relapsed lymphoma should be strongly encouraged to participate inclinical trials in efforts to gain understanding of how best to treat this complex disease.If you have any questions or have a patient who may be appropriate for these studies,please feel free to contact Dr. Nancy Bartlett or Dr. Nina Wagner-Johnston at(314) 362-5654. We truly appreciate your referrals and support of these studies.2

WelcomeThe Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School ofMedicine is pleased to announce the addition of Kenneth Carson, M.D. and Nina Wagner-Johnston, M.D.to its hematologic malignancies team.Kenneth Carson, M.D.Dr. Carson received his medical degree from the University of SouthernCalifornia and completed a residency in internal medicine at Duke University.Prior to joining the Washington University faculty, he completed a clinicalfellowship in hematology and oncology and a postdoctoral researchfellowship in health services at Northwestern University in Chicago.Dr. Carson will be seeing patients with hematologic malignancies atSiteman’s main campus and west county location. His research focuses onissues of cost, quality, and access to oncology care. Dr. Carson joins theWashington University faculty as an Instructor of Medicine.Kenneth Carson, M.D.Nina Wagner-Johnston, M.D.Dr. Wagner-Johnston graduated from the University of Chicago School ofMedicine, where she also received residency training in internal medicine.She completed a fellowship in medical oncology at Johns Hopkins Universityin Baltimore. During her fellowship training, she evaluated clonal Ig DNAin plasma from patients with AIDS-related lymphomas. Her interestsinclude prognostic biomarkers and clinical trial development for patientswith lymphoma and AIDS-related malignancies. Dr. Wagner-Johnston seesnontransplant lymphoma patients at Siteman’s main campus and joins theWashington University faculty as an Assistant Professor of Medicine.Nina Wagner-Johnston, M.D.Continuing Medical Education:Advances in Diagnosis and Treatment of Hematologic MalignanciesSeptember 20, 2008Four Seasons Hotel, St. Louis, MissouriSiteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine is hosting an educational symposiumentitled “Advances in Diagnosis and Treatment of Hematologic Malignancies”. The symposium will take place on Saturday, September20 at the Four Seasons Hotel in St. Louis, Missouri.The annual symposium provides the audience with updated information on cancer treatment and diagnosis through discussions onhematological malignancies, and to host a guest speaker, Dr. Dennis Confer who is the Chief Medical Officer for the National MarrowDonor Program.In addition to the conference, we are hosting our 15th Annual Bone Marrow Transplant Patient Celebration on Saturday, September20, in the ballroom of the St. Louis Four Seasons Hotel. You and a guest are invited to attend this event and honor our survivors.Please join us for a private physician reception an hour prior to the patient celebration, in the “Gateway Room” of the hotel.If you are interested in attending the symposium, please register at http://cme.wustl.edu. Also, please RSVP for the patientcelebration and private physician reception by calling 314-747-7222 or 800-600-3606 by September 10.3

Hematologic MalignanciesLeukemia, Lymphoma, Myelomaand Stem Cell TransplantationClinical TrialsTo learn more about the clinical studies, or to enroll a patient,please contact the listed study coordinator at 314-454-8377.AML, newly diagnosedAcute Leukemia /MDSCALGB 10503 PI: Ravi Vij Study Coordinator:Ryan MonahanPhase II Study of Maintenance Therapy With DecitabineFollowing Standard Induction and Cytogenetic Risk-AdaptedIntensification in Previously Untreated Patients With AML< 60 Years.Notes: Newly dx de novo AML age 18-59, randomized to decitabinemaintenance after induction and risk adapted consolidation basedon cytogenetics to either HiDAC or auto transplant08-0126 PI: Ravi Vij Study Coordinator:Ryan MonahanSWOG S0521— A Randomized Trial of Maintenance VersusObservation for Patients with Previously Untreated Low andIntermediate Risk Acute Promyelocytic Leukemia (APL),Phase III.Notes: Low or intermediate risk APL 18 years and older withno prior systemic therapy or recurrent disease.06-0907 PI: Ravi Vij Study Coordinator:Alissa NelsonPhase II Trial of Lenalidomide in Older Patients (> 60 years)with Untreated Acute Myeloid Leukemia without Chromosome5q AbnormalitiesAML, relapsed refractory07-0227 PI: Geoffrey Uy Study Coordinator:Sandra LopezA Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide andCytarabine (AMD3100+MEC) in Relapsed or Refractory AML.Notes: Age 18-65 with either primary refractory AML, relapsed AMLwith initial CR less than 1 yr or in 2nd relapse or higher08-0017 PI: Keith Stockerl-GoldsteinStudy Coordinator:Alissa NelsonOpen Label Randomized Controlled Dose Escalating Phase IIStudy of AS1411 Combined with Cytarabine in the Treatmentof Patients with Primary Refractory or Relapsed Acute MyeloidLeukemia (AS1411-C-201).Notes: Refractory or relapsed AML and 18 years of age or older.MDS/AML, otherP2C 05-1159PI: Amanda CashenPhase II Study of the Histone Deacetylase Inhibitor PXD101for the Treatment of Myelodysplastic SyndromeNotes: 18 years old and up with a diagnosis of MDS, no morethan 2 previous lines of therapy and either ineligible or refusedallo transplant.08-0172 PI: Geoffrey Uy Study Coordinator:Alissa NelsonA Phase I/II Study of LBH589 plus Decitabine for PatientsAge > 60 Years with High Risk MDS or AMLNotes: Age > 60 with MDS (IPSS>2) or AML with no prior treatmentwith a hypomethylating agentCALGB 100103 PI: Ravi Vij Study Coordinator:Ryan MonahanA Phase II Study Of Allogeneic Transplant For Older PatientsWith AML In First Morphologic Complete Remission UsingA Non-Myeloablative Preparative Regimen.Notes: CR1, Fludarabine, Busulfan, Thymoglobulin conditioning07-0643 PI: John DiPersio Study Coordinator:Jeremy GabrielA Phase II Study of Active Immunotherapy With GRNVAC1,Autologous Mature Dendritic Cells Transfected With mRNAEncoding Human Telomerase Reverse Transcriptase, inPatients With Acute Myelogenous Leukemia in CompleteClinical Remission.Notes: Age 18-65 with AML in 1st or 2nd CR using dendriticcell vaccine directed against telomerase (hTERT)08-X139 PI:Camille Abboud Study Coordinator:Ryan MonahanPhase I Study of Oral Clofarabine Consolidation in Adults Aged60 and Older with Acute Myeloid LeukemiaStudy Coordinator:07-0916 PI: Ravi VijLiz ProcknowA Phase II study of intravenous Decitabine in combinationwith Arsenic Trioxide and Ascorbic Acid in patients withmyelodysplastic syndromesNotes: MDS defined by FAB classification.ALLCALGB 10403 PI: Ravi Vij Study Coordinator:Ryan MonahanAn Intergroup Phase II Clinical Trial for Adolescents and Youngadults with Untreated Acute Lymphoblastic Leukemia.Notes: Newly diagnosed and untreated ALL between the age of16 and 29.4

Hematological Malignancies is published by The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington UniversitySchool of Medicine. The Siteman Cancer Center is a Comprehensive Cancer Center designation from the National Cancer Institute (NCI) andmembership in the National Comprehensive Cancer Network (NCCN).Editors: Geoffrey Uy, M.D. and Ryan Monahan | Article Contributors: Nancy Bartlett, M.D. and Nina Wagner-Johnston, M.D. |Production Manager: Angela BenassiFollicularNON-HODGKIN LYMPHOMA (NHL)CALGB 50401 PI: Nancy L.BartlettStudy Coordinator:Rachael KeeleyA Randomized Phase II trial of Rituximab vs. Lenalidomide(Revlimid TM , CC-5013) (IND # 73034) vs. Rituximab + Lenalidomidein Recurrent Follicular Non-Hodgkin Lymphoma (NHL) ThatIs Not Rituximab-Refractory (Arm A, Rituximab Alone, waspermanently closed effective 9/15/2007)Notes: Patients must have been treated with rituximab either aloneor in combination with chemotherapy. The last prior treatmentregimen need not include rituximab but must have progressed>6 months from their last rituximab dose.CALGB 50701 PI: Nancy L.BartlettStudy Coordinator:Justina FirstA Phase II Trial of Extended Induction Epratuzumab (Anti-CD22Monoclonal Antibody) Plus Rituximab in Previously UntreatedFollicular Non-Hodgkin’s Lymphoma07-0889 PI: Nancy L.BartlettStudy Coordinator:Rachael KeeleyA Phase II, Single-Arm, Open-Label Study of the Safety,Pharmacokinetics, and Efficacy of Multiple Doses of APOMABAdministered Intravenously in Combination with Rituximab inPatients with Follicular, CD20-positive B-cell non-Hodgkin’sLymphoma that has Progressed Following Previous Rituximab TherapyNotes: Patients must have had a complete response, partialresponse, or stable disease lasting more than 6 months aftercompletion of their most recent rituximab-containing regimen.08-0332 PI: Amanda Cashen Study Coordinator:Rachael KeeleyA Phase II Study of Bortezomib in Combination withBendamustine and Rituximab in Subjects with Relapsed orRefractory Follicular LymphomaNotes: Prior treatment with Bortezomib or Bendamustine is notallowed; at least 4 prior doses of Rituximab; prior allogeneic stemcell transplant not allowed.Large CellCALGB 50303 PI: Nancy L.BartlettStudy Coordinator:Sarah LarsonPhase III Randomized Study of R-CHOP vs. Dose-AdjustedEPOCH-R with Molecular Profiling in Untreated De Novo DiffuseLarge B-Cell LymphomasNotes: Patients must have a new biopsy if fresh/frozen tissue wasnot available from their first biopsy, unless contraindicated.07-1073 PI: Nancy L.BartlettStudy Coordinator:Justina FirstA Randomized Phase IIb Placebo-Controlled Study of R-ICEChemotherapy (Rituximab, Ifosfamide, Carboplatin, andEtoposide) with and without SGN-40 (Anti-CD40 humanizedmonoclonal antibody) for Second-line Treatment of Patients withDiffuse Large B-Cell LymphomaNotes: Patients must have achieved a complete response, partialresponse, or stable disease from their most recent prior therapyconsisting of combination chemotherapy and rituximab.07-0927 PI: Nancy L.BartlettStudy Coordinator:Rachael KeeleyA Phase II Multicenter, Open-Label Study of YM155 in RefractoryDiffuse Large B-Cell Lymphoma (DLBCL) SubjectsNotes: Patients must have been refractory to the lasttreatment regimen.08-0500 PI: Nancy L.BartlettStudy Coordinator:Sarah LarsonA Phase Ib Study of SGN-40 in Combination with Rituximab andGemcitabine for the Treatment of Patients with Relapsed orRefractory Diffuse Large B-Cell LymphomaMantle CellCALGB 50403 PI: Nancy L.BartlettStudy Coordinator:Rachael KeeleyA Randomized Phase II Trial of Maintenance vs. ConsolidationBortezomib Therapy Following Aggressive Chemo-Immunotherapyand Autologous Stem Cell Transplant for Previously UntreatedMantle Cell LymphomaNotes: Patients must be between the ages of 18 and 69 years withany stage (I-IV).CALGB 50501 PI: Nancy L.BartlettStudy Coordinator:Donna SeckfortA Phase II Trial of Bortezomib (NSC #681239) + Lenalidomide(Revlimid TM , CC-5013) (NSC#703813) For Relapsed/RefractoryMantle Cell LymphomaNotes: Patients may not have received prior bortezomib orlenalidomide therapy.AIDS/HTLVAMC 047 PI: Lee Ratner Study Coordinator:Lee RatnerA Phase II Trial of Doxil, Rituximab, Cyclophosphamide,Vincristine, and Prednisone (DR-COP) in Patients with NewlyDiagnosed AIDS-Associated B-Cell Non-Hodgkin’s LymphomaAMC 048 PI: Lee Ratner Study Coordinator:Lee RatnerProspective Phase II Study of a High Dose, Short CourseRegimen (R-CODOX-M/IVAC) Including Central Nervous System(CNS) Penetration and Intensive Intrathecal (IT) Prophylaxis inHIV-Associated Burkitt’s and Atypical Burkitt’s Lymphoma.(continued on page 6)5

Hematologic MalignanciesClinical Trials (continued)Leukemia, Lymphoma, Myelomaand Stem Cell TransplantationPrimary CNSRTOG 0227PI: DavidMansurStudy Coordinator:Shannon RickeyPhase I/II Study of Pre-Irradiation Chemotherapy withMethotrexate, Rituximab, and Temozolomide and Post-Irradiation Temozolomide for Primary Central NervousSystem LymphomaAll Lymphoma Histologies08-0494 PI: Nancy L.BartlettStudy Coordinator:Justina FirstA Phase I/II Dose Escalation Study of the Pan-HistoneDeacetylase (HDAC) Inhibitor PCI-24781 in LymphomaNotes: Patients must have had no more than 4 prior therapies; priorallogeneic transplant not allowed.08-0543 PI: Nancy L.BartlettStudy Coordinator:Justina FirstA Phase I/IIa Open-Label Study of Pralatrexate and Gemcitabinewith Vitamin B12 and Folic Acid Supplementation in Patients withRelapsed or Refractory Lymphoproliferative MalignanciesNotes: Patients must have at least 1 prior treatment; no priorallogeneic transplant; patients must have relapsed > 100 days fromautologous transplant.T-Cell08-0170 PI: Nancy L.BartlettStudy Coordinator:Sarah LarsonA Phase I Dose Escalation Study of Weekly SGN-35 Alone andIn Combination with Gemcitabine in Patients with Relapsed/Refractory CD30-Positive Hematologic MalignanciesNotes: Patients with relapsed/refractory ALCL are eligible forthis trial.07-1079 PI: Nancy L.BartlettStudy Coordinator:Justina FirstA Phase 1, Open-Label Study of Pralatrexate with Vitamin B 12and Folic Acid Supplementation in Patients with Relapsed orRefractory Cutaneous T-Cell LymphomaNotes: Patients must have had at least 1 prior therapy. Patientswith mycosis fungoides and Sezary syndrome are eligible.08-0443 PI: Nancy L.BartlettStudy Coordinator:Justina FirstTreatment of Peripheral T-Cell Lymphoma with AggressiveInduction Chemotherapy Followed by Autologous Stem CellTransplant using Denileukin Diftitox (Ontak) for in-vivo Purgingand Post-Transplant Therapy: A Multicenter Phase II Clinical TrialNotes: For patients with previously untreated T-Cell Lymphoma orcould have received up to 1 prior cycle of chemotherapy07-0878 PI: Nancy L.BartlettStudy Coordinator:Rachael KeeleySingle Agent Phase II Study of Forodesine (BCX1777) in theTreatment of Cutaneous T-Cell LymphomaNotes: Patients must have progressed/recurred following 3 formsof systemic therapy, one of which must have been oral bexaratone(unless it was not tolerated or medically contraindicated). Patientsmust have stage IB-IVA CTCL; mycosis fungoides or Sezarysyndrome are eligible.HODGKIN LYMPHOMA (HL)08-0170 PI: Nancy L.BartlettStudy Coordinator:Sarah LarsonA Phase I Dose Escalation Study of Weekly SGN-35 Alone andin Combination with Gemcitabine in Patients with Relapsed/Refractory CD30-Positive Hematologic MalignanciesNotes: Patients with recurrent Hodgkin’s lymphoma must havefailed systemic therapy either as induction for advanced stagedisease or salvage therapy after initial radiotherapy for early stageand were ineligible for, refused treatment by or previously receivedstem cell transplant.07-0233 PI: Nancy L.BartlettStudy Coordinator:Sarah LarsonA Phase II Multicenter Study of Lenalidomide in Relapsed orRefractory Classical Hodgkin LymphomaNotes: Patients must have recurred after at least 1 prior therapy.Patients with any stage and who have had prior autologous orallogeneic stem cell transplant are eligible.CALGB 50602 PI: Nancy L.BartlettStudy Coordinator:Sarah LarsonA Phase II Study of Galiximab in Patients with Relapsed/Refractory Hodgkin’s LymphomaNotes: Patients must have had at least 2 prior treatments; priorautologous and/or allogeneic stem cell transplant is allowed.Chronic Lymphocytic Leukemia (CLL)CALGB 10404 PI: Nancy L.BartlettStudy Coordinator:Donna SeckfortA Randomized Phase II Study of Three Fludarabine/antibodyCombinations for Patients with Symptomatic, PreviouslyUntreated Chronic Lymphocytic LeukemiaNotes: For previously untreated CLL patients requiring therapy(symptomatic, intermediate or high-risk by Rai staging system).CALGB 10501 PI: Nancy L.BartlettStudy Coordinator:Donna SeckfortA Phase III Intergroup CLL Study of Asymptomatic Patients withUntreated Chronic Lymphocytic Leukemia Randomized to EarlyIntervention Versus Observation with Later Treatment in theHigh Risk Genetic Subset with IGV H Unmutated DiseaseNotes: For patients who are within 6 months of their initialdiagnosis, asymptomatic and low risk by Rai staging system.6

Multiple MyelomaCALGB 100104 PI: Ravi Vij Study Coordinator:Ryan MonahanA Phase III Randomized, Double-Blind Study of MaintenanceTherapy with CC-5013 or Placebo Following AutologousStem Cell Transplantation for Multiple MyelomaNotes: At least stage 1 MM, 2 months stable following therapy,no more than 12 months total prior therapy for MM.07-1136 PI: Ravi Vij Study Coordinator:Deborah GensburgPhase I/II Trial of combination CCI-779 (Temsirolimus) andBortezomib (VELCADE) in Relapsed and/or Relapsed/RefractoryMultiple Myeloma (MMRC CCI-779).Notes: Relapsed or relapsed/refractory Multiple Myeloma patients18 years old or greater with measurable disease.07-0775 PI: Ravi Vij Study Coordinator:Mark FialaAn Open-label, Single-arm, Phase 2 Study of Carfilzomib inPatients with Relapsed and Refractory Multiple MyelomaNotes: Ages 18 and older with a previous response with relapseand refractory to last line of therapy, must have been treated withbortezomib and either thalidomide or lenalidomide.07-0776 PI: Ravi Vij Study Coordinator:Mark FialaAn Open-label, Single-arm, Phase 2 Study of Carfilzomib inPatients with Relapsed Multiple MyelomaNotes: Ages 18 and older with a response to their prior line oftherapy.PDL PI: Ravi Vij Study Coordinator:Deborah GensburgA Phase 1b, Multicenter, Open-label, Dose-escalation Study ofHuLuc63 (Humanized Anti-CS1 Monoclonal IgG1 Antibody) inCombination with Lenalidomide and Dexamethasone in subjectswith Relapsed Multiple MyelomaGeneralTransplantCTN 0201 PI: John DiPersio Study Coordinator:Jeremy GabrielA Phase III Randomized, Multicenter Trial ComparingG-CSF Mobilized Peripheral Blood Stem Cell with MarrowTransplantation from HLA Compatible Unrelated DonorsNotes: AML, ALL, CML, MDS03-0349 PI: John DiPersio Study Coordinator:Sandra LopezA Phase I/II Study Evaluating The Safety And Efficacy OfAMD3100 For The Mobilization And Transplantation OfHLA-Matched Sibling Donor Hematopoietic Stem Cells InPatients With Advanced Hematological MalignanciesNotes: Patients age 18-70 with a 6/6 matched sibling donor.08-0011 PI: John DiPersio Study Coordinator:Liz ProcknowA Multicenter, Prospective Trial to Evaluate the Role of NKCell Kir Epitope Mismatch on Mortality and Disease Relapse inT-Cell Depleted Hematopoietic Stem Cell Transplantation fromHLA-C Mismatched, Unrelated Donors for Myeloid Malignancies(MT2004-04).GVHDCTN 0402 PI: John DiPersio Study Coordinator:Jeremy GabrielA Phase III Randomized, Multicenter Trial Comparing Sirolimus/Tacrolimus with Tacrolimus/Methotrexate as GVHD ProphylaxisAfter HLA-Matched, Related Peripheral Blood Stem CellTransplantation — BMT CTN 0402Notes: AML, ALL, CML, or MDS ages 2-60 with a performance statusof 70 and a 6/6 matched sib.08-0072 PI: PeterWesterveltStudy Coordinator:Jeremy GabrielA Phase III, Randomized, Double-Blind, Placebo-ControlledStudy to Evaluate the Efficacy and Safety of Prochymal (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells)Infusion in Combination with Corticosteroids for the Treatmentof newly diagnosed Acute GVHD.Supportive care03-1192 PI: John DiPersio Study Coordinator:Jeremy GabrielA Pilot Study Evaluating the Efficacy and Safety of the OralNeurokinin-1 Antagonist, Aprepitant, in Combination withOndansetron and Dexamethasone in Patients UndergoingAutologous Peripheral Blood Stem Cell TransplantationNotes: Patients age 18-70 with a diagnosis of Hodgkin’s Disease,Non-Hodgkin’s Lymphoma, Multiple Myeloma, and Amyloidosis.7