|
|
 Previous Article | Table of Contents | Next Article 
Phase I Trial of a Ligand Fusion-Protein (DAB389IL-2) in
Lymphomas Expressing the Receptor for Interkeukin-2
C.F. LeMaistre,
Mansoor N. Saleh,
Timothy M. Kuzel,
Francine Foss,
Leonidas C. Platanias,
Gary Schwartz,
Mark Ratain,
Alain Rook,
Cesar O. Freytes,
Fiona Craig,
James Reuben, and
Jean C. Nichols
From the South Texas Cancer Institute, San Antonio, TX; The
University of Alabama, Birmingham, AL; Northwestern University Medical
School, Chicago, IL; Boston University Medical Center, Boston, MA;
Loyola University Medical Center, Maywood, IL; Hines Veterans Affairs
Hospital, Hines, IL; Beth Israel Hospital, Boston, MA; University of
Chicago, Chicago, IL; Hospital of the University of Pennsylvania,
Philadelphia, PA; University of Texas Health Science Center, San
Antonio, TX; MD Anderson Cancer Center, Houston, TX; and Seragen, Inc,
Hopkinton, MA.
The purpose of this study was to evaluate the safety,
tolerability, pharmacokinetics, and possible antitumor activity of a ligand fusion-protein, DAB389IL-2, in a phase I trial. This
was a multicenter, open-label, dose-escalation trial. Patients with preserved organ function and histologically confirmed relapsed cutaneous T-cell lymphoma (CTCL), other non-Hodgkin's lymphomas (NHL),
or Hodgkin's disease (HD) were eligible if their cancer was shown to
express the interleukin (IL)-2 receptor by an immunohistochemical assay
for the p55 or the p75 subunit. Patients received up to eight courses
of DAB389IL-2 given as a short intravenous infusion daily
for 5 days with subsequent courses every 21 days. The maximum tolerated
dose (MTD) and tumor response was determined according to standard
criteria. Seventy-three patients (44 men/29 women), aged 16 to 81 years
(mean, 50.7) with CTCL (n = 35), NHL (n = 17), and HD (n = 21)
were enrolled. The patients were extensively treated, failing 0 to 15 previous therapies (median, 4). Patients received one to six courses
(mean, 3.3) of DAB389IL-2 over a range of 3 to 31 µg/kg/day. The dose-limiting toxicity was asthenia, establishing the
maximum tolerated dose of 27 µg/kg/day. Approximately half of all
patients had significant titers of antibody to diphtheria toxin or to
DAB389IL-2 at the time of enrollment compared with 92%
with titers at the end of treatment. The presence of antibody did not
preclude clinical response. There were five complete (CR) and eight
partial (PR) remissions in patients with CTCL with one CR and two PR
occurring in NHL. The median time to response was 2 months and the
duration of response was 2 to 39+ months. No responses were
documented in patients with HD. DAB389IL-2 is well tolerated with an MTD of 27 µg/kg/day. This ligand fusion-protein showed antitumor effects in patients with IL-2 receptor expressing CTCL
and NHL. Additional trials in these diseases are warranted.
Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 399-405
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. T. Litzinger, R. Fernando, T. J. Curiel, D. W. Grosenbach, J. Schlom, and C. Palena
IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity
Blood,
November 1, 2007;
110(9):
3192 - 3201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. E. Kennedy, T. K. Bera, Q.-C. Wang, M. Gallo, W. Wagner, M. G. Lewis, E. A. Berger, and I. Pastan
Anti-HIV-1 immunotoxin 3B3(Fv)-PE38: enhanced potency against clinical isolates in human PBMCs and macrophages, and negligible hepatotoxicity in macaques
J. Leukoc. Biol.,
November 1, 2006;
80(5):
1175 - 1182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Ghori, K. D. Polder, L. C. Pinter-Brown, A. O. Hoff, R. F. Gagel, S. I. Sherman, and M. Duvic
Thyrotoxicosis after Denileukin Diftitox Therapy in Patients with Mycosis Fungoides
J. Clin. Endocrinol. Metab.,
June 1, 2006;
91(6):
2205 - 2208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Rizvi, A. M. Evens, M. S. Tallman, B. P. Nelson, and S. T. Rosen
T-cell non-Hodgkin lymphoma
Blood,
February 15, 2006;
107(4):
1255 - 1264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Foss, M. F. Demierre, and G. DiVenuti
A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma
Blood,
July 15, 2005;
106(2):
454 - 457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Kreitman
Confirmation and prevention of targeted toxicity by a recombinant fusion toxin
Mol. Cancer Ther.,
December 1, 2004;
3(12):
1691 - 1692.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. H. Dang, F. B. Hagemeister, B. Pro, P. McLaughlin, J. E. Romaguera, D. Jones, B. Samuels, F. Samaniego, A. Younes, M. Wang, et al.
Phase II Study of Denileukin Diftitox for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
October 15, 2004;
22(20):
4095 - 4102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. E. Frankel, D. R. Fleming, P. D. Hall, B. L. Powell, J. H. Black, C. Leftwich, and R. Gartenhaus
A Phase II Study of DT Fusion Protein Denileukin Diftitox in Patients with Fludarabine-refractory Chronic Lymphocytic Leukemia
Clin. Cancer Res.,
September 1, 2003;
9(10):
3555 - 3561.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Schnell, P. Borchmann, J. O. Staak, J. Schindler, V. Ghetie, E. S. Vitetta, and A. Engert
Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin's lymphoma
Ann. Onc.,
May 1, 2003;
14(5):
729 - 736.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen
Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential
Pharmacol. Rev.,
March 1, 2003;
55(1):
133 - 166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Gorgun and F. Foss
Immunomodulatory effects of RXR rexinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox
Blood,
July 30, 2002;
100(4):
1399 - 1403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Senchenkov, T.-Y. Han, H. Wang, A. E. Frankel, T. J. Kottke, S. H. Kaufmann, and M. C. Cabot
Enhanced ceramide generation and induction of apoptosis in human leukemia cells exposed to DT388-granulocyte-macrophage colony-stimulating factor (GM-CSF), a truncated diphtheria toxin fused to human GM-CSF
Blood,
September 15, 2001;
98(6):
1927 - 1934.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. E. Schnipper and T. B. Strom
A Magic Bullet for Cancer -- How Near and How Far?
N. Engl. J. Med.,
July 26, 2001;
345(4):
283 - 284.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Duvic, K. Hymes, P. Heald, D. Breneman, A. G. Martin, P. Myskowski, C. Crowley, and R. C. Yocum
Bexarotene Is Effective and Safe for Treatment of Refractory Advanced-Stage Cutaneous T-Cell Lymphoma: Multinational Phase II-III Trial Results
J. Clin. Oncol.,
May 1, 2001;
19(9):
2456 - 2471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Olsen, M. Duvic, A. Frankel, Y. Kim, A. Martin, E. Vonderheid, B. Jegasothy, G. Wood, M. Gordon, P. Heald, et al.
Pivotal Phase III Trial of Two Dose Levels of Denileukin Diftitox for the Treatment of Cutaneous T-Cell Lymphoma
J. Clin. Oncol.,
January 15, 2001;
19(2):
376 - 388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Fehniger and M. A. Caligiuri
Interleukin 15: biology and relevance to human disease
Blood,
January 1, 2001;
97(1):
14 - 32.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kobayashi, J. A. Carrasquillo, C. H. Paik, T. A. Waldmann, and Y. Tagaya
Differences of Biodistribution, Pharmacokinetics, and Tumor Targeting between Interleukins 2 and 15
Cancer Res.,
July 1, 2000;
60(13):
3577 - 3583.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. R. Husain and R. K. Puri
Interleukin-13 fusion cytotoxin as a potent targeted agent for AIDS-Kaposi's sarcoma xenograft
Blood,
June 1, 2000;
95(11):
3506 - 3513.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Kreitman, W. H. Wilson, J. D. White, M. Stetler-Stevenson, E. S. Jaffe, S. Giardina, T. A. Waldmann, and I. Pastan
Phase I Trial of Recombinant Immunotoxin Anti-Tac(Fv)-PE38 (LMB-2) in Patients With Hematologic Malignancies
J. Clin. Oncol.,
April 1, 2000;
18(8):
1622 - 1636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Messmann, E. S. Vitetta, D. Headlee, A. M. Senderowicz, W. D. Figg, J. Schindler, D. F. Michiel, S. Creekmore, S. M. Steinberg, D. Kohler, et al.
A Phase I Study of Combination Therapy with Immunotoxins IgG-HD37-Deglycosylated Ricin A Chain (dgA) and IgG-RFB4-dgA (Combotox) in Patients with Refractory CD19(+), CD22(+) B Cell Lymphoma
Clin. Cancer Res.,
April 1, 2000;
6(4):
1302 - 1313.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. J. Kreitman, W. H. Wilson, D. Robbins, I. Margulies, M. Stetler-Stevenson, T. A. Waldmann, and I. Pastan
Responses in Refractory Hairy Cell Leukemia to a Recombinant Immunotoxin
Blood,
November 15, 1999;
94(10):
3340 - 3348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
