A phase 1 trial of the Fc-engineered CD19 antibody XmAb5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed CLL

Blood

Volumn 124, Issue 24, 2014, Pages 3553-3560

  Woyach, Jennifer A ^a   Awan, Farrukh ^a   Flinn, Ian W ^b   Berdeja, Jesus G ^b   Wiley, Elizabeth ^a   Mansoor, Sharmeen ^c   Huang, Ying ^a   Lozanski, Gerard ^c   Foster, Paul A ^d   Byrd, John C ^a  

^a THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

^b SARAH CANNON RESEARCH INSTITUTE   (United States)

^c OHIO STATE UNIVERSITY   (United States)

^d Xencor Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTILEUKEMIC AGENT; ASPARTATE AMINOTRANSFERASE; CD19 ANTIBODY; DEXAMETHASONE; DIPHENHYDRAMINE; FC RECEPTOR; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; MONOCLONAL ANTIBODY; PARACETAMOL; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; STEROID; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG; XMAB 5574; ANTINEOPLASTIC AGENT; CANCER ANTIBODY; CD19 ANTIGEN; IMMUNOGLOBULIN CONSTANT REGION;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; AUTOIMMUNE HEMOLYTIC ANEMIA; BINDING AFFINITY; CANCER IMMUNOTHERAPY; CANCER PATIENT; CHEMOTHERAPY INDUCED NAUSEA AND VOMITING; CHILL; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL ARTICLE; COMPUTER ASSISTED TOMOGRAPHY; DIARRHEA; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG FEVER; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FLOW CYTOMETRY; FOLLOW UP; HUMAN; HYPERURICEMIA; HYPOCALCEMIA; IMMUNOGLOBULIN BLOOD LEVEL; INFUSION RATE; LEUKEMIA RELAPSE; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; NATURAL KILLER CELL; NEUTROPENIA; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL; PHYSICAL EXAMINATION; RECEPTOR BINDING; SENSORY NEUROPATHY; SIDE EFFECT; STEADY STATE; STEROID THERAPY; T LYMPHOCYTE; THROMBOCYTOPENIA; TREATMENT RESPONSE; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; TUMOR LYSIS SYNDROME; VOLUME OF DISTRIBUTION; ADMINISTRATION AND DOSAGE; BLOOD; CLINICAL TRIAL; HALF LIFE TIME; IMMUNOGLOBULIN CONSTANT REGION; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MIDDLE AGED; MULTICENTER STUDY; RECURRENT DISEASE; TIME; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEOPLASM; ANTIGENS, CD19; ANTINEOPLASTIC AGENTS; FEMALE; HALF-LIFE; HUMANS; IMMUNOGLOBULIN CONSTANT REGIONS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; RECURRENCE; TIME FACTORS; TOMOGRAPHY, X-RAY COMPUTED;

EID: 84915756978     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-08-593269     Document Type: Article

References (30)

1. Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343(24):1750-1757.
2. O'Brien SM, Kantarjian H, Thomas DA, et al. Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol. 2001;19(8):2165-2170.
3. Byrd JC, Murphy T, Howard RS, et al. Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol. 2001;19(8):2153-2164.
4. Byrd JC, Peterson BL, Morrison VA, et al. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood. 2003;101(1):6-14.
5. Byrd JC, Rai K, Peterson BL, et al. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood. 2005;105(1):49-53.
6. Wierda W, O'Brien S, Wen S, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005;23(18):4070-4078.
7. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164-1174.
8. Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28(10):1749-1755.
9. Osterborg A, Dyer MJ, Bunjes D, et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia. J Clin Oncol. 1997;15(4):1567-1574.
10. Baban B, Hansen AM, Chandler PR, et al. A minor population of splenic dendritic cells expressing CD19 mediates IDO-dependent T cell suppression via type I IFN signaling following B7 ligation. Int Immunol. 2005;17(7):909-919.
11. Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 1995;18(5-6):385-397.
12. Carter RH, Doody GM, Bolen JB, Fearon DT. Membrane IgM-induced tyrosine phosphorylation of CD19 requires a CD19 domain that mediates association with components of the B cell antigen receptor complex. J Immunol. 1997;158(7):3062-3069.
13. Sato S, Miller AS, Howard MC, Tedder TF. Regulation of B lymphocyte development and activation by the CD19/CD21/CD81/Leu 13 complex requires the cytoplasmic domain of CD19. J Immunol. 1997;159(7):3278-3287.
14. Hurwitz CA, Loken MR, Graham ML, et al. Asynchronous antigen expression in B lineage acute lymphoblastic leukemia. Blood. 1988;72(1):299-307.
15. Kaleem Z, Crawford E, Pathan MH, et al. Flow cytometric analysis of acute leukemias. Diagnostic utility and critical analysis of data. Arch Pathol Lab Med. 2003;127(1):42-48.
16. Monaghan SA, Peterson LC, James C, et al. Pan B-cell markers are not redundant in analysis of chronic lymphocytic leukemia (CLL). Cytometry B Clin Cytom. 2003;56(1):30-42.
17. Thalhammer-Scherrer R, Mitterbauer G, Simonitsch I, et al. The immunophenotype of 325 adult acute leukemias: relationship to morphologic and molecular classification and proposal for a minimal screening program highly predictive for lineage discrimination. Am J Clin Pathol. 2002;117(3):380-389.
18. Lazar GA, Dang W, Karki S, et al. Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci USA. 2006;103(11):4005-4010.
19. Horton HM, Bernett MJ, Pong E, et al. Potent in vitro and in vivo activity of an Fc-engineered anti-CD19 monoclonal antibody against lymphoma and leukemia. Cancer Res. 2008;68(19):8049-8057.
20. Awan FT, Lapalombella R, Trotta R, et al. CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain-engineered monoclonal antibody. Blood. 2010;115(6):1204-1213.
21. Hallek M, Cheson BD, Catovsky D, et al; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111(12):5446-5456.
22. Byrd JC, Gribben JG, Peterson BL, et al. Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol. 2006;24(3):437-443.
23. Woyach JA, Heerema NA, Zhao J, et al. Dic(17;18)(p11.2;p11.2) is a recurring abnormality in chronic lymphocytic leukaemia associated with aggressive disease. Br J Haematol. Mar;148(5):754-759.
24. Cheson BD, Pfistner B, Juweid ME, et al; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579-586.
25. Huhn D, von Schilling C, Wilhelm M, et al; German Chronic Lymphocytic Leukemia Study Group. Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood. 2001;98(5):1326-1331.
26. Itälä M, Geisler CH, Kimby E, et al. Standard-dose anti-CD20 antibody rituximab has efficacy in chronic lymphocytic leukaemia: results from a Nordic multicentre study. Eur J Haematol. 2002;69(3):129-134.
27. Cartron G, de Guibert S, Dilhuydy MS, et al. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014;124(14):2196-2202.
28. Byrd JC, Pagel JM, Awan FT, et al. A phase 1 study evaluating the safety and tolerability of otlertuzumab, an anti-CD37 mono-specific ADAPTIR therapeutic protein in chronic lymphocytic leukemia. Blood. 2014;123(9):1302-1308.
29. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-1110.
30. Kohrt HE, Sagiv-Barfi I, Rafiq S, et al. Ibrutinib (PCI-32765) antagonizes rituximab-dependent NK cell-mediated cytotoxicity. Blood. 2014;123(12):1957-1960.