Universität zu Köln

Schweighofer, Carmen D., Tuchscherer, Armin, Sperka, Sabine, Meyer, Thorsten, Rattel, Benno, Stein, Sandra, Ismail, Semra, Elter, Thomas, Staib, Peter, Reiser, Marcel and Hallek, Michael (2012). Clinical safety and pharmacological profile of the HLA-DR antibody 1D09C3 in patients with B cell chronic lymphocytic leukemia and lymphoma: results from a phase I study. Cancer Immunol. Immunother., 61 (12). S. 2367 - 2374. NEW YORK: SPRINGER. ISSN 0340-7004

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Abstract

1D09C3 is a human monoclonal IgG4-type antibody against human leukocyte antigen-DR (HLA-DR) which has demonstrated pro-apoptotic activity against lymphoid tumors in vitro and in vivo. We report results from a phase I dose-escalation study which aimed to identify tolerated dosing, and the pharmacokinetic and pharmacodynamic profile of 1D09C3. Fourteen patients with relapsed/refractory B cell type leukemia/lymphoma were treated and followed after up to 4 weekly infusions of 1D09C3, administered in 6 dose levels at 0.25-8 mg/kg/day. Treatment was tolerated well with mostly mild side effects. The most common grade III-IV toxicities were hematological events observed in 4 patients. In one patient, treated at 8.0 mg/kg/day, a dose limiting toxicity occurred, identified as an invasive catheter-related infection. Adverse events resolved completely without long-term sequelae. 1D09C3 reduced peripheral blood B cells and monocytes by a median of 73-81 % in all patients, with a nadir reached 30-60 min after infusion and sustained for < 96 h. Granulocytes and natural killer cells predominantly increased with variable time courses. Pharmacokinetic assessments showed detectable drug concentrations at doses 4-8 mg/kg/day and a terminal half-life of 0.7-7.9 h. Effective saturation of HLA-DR on peripheral blood B cells/monocytes was achieved, varying consistently with available serum concentrations and the cell-reducing activity of 1D09C3. In summary, 1D09C3 could be administered safely in patients with advanced B cell malignancies. Pharmacodynamic studies demonstrated a strong dose dependent but transient reduction of peripheral blood B cells and monocytes, consistent with a short drug serum availability.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schweighofer, Carmen D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tuchscherer, Armin UNSPECIFIED UNSPECIFIED UNSPECIFIED Sperka, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Rattel, Benno UNSPECIFIED UNSPECIFIED UNSPECIFIED Stein, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Ismail, Semra UNSPECIFIED UNSPECIFIED UNSPECIFIED Elter, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Staib, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiser, Marcel UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-477680
DOI:	10.1007/s00262-012-1362-x
Journal or Publication Title:	Cancer Immunol. Immunother.
Volume:	61
Number:	12
Page Range:	S. 2367 - 2374
Date:	2012
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	0340-7004
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FAB-ARM EXCHANGE; COMPLEX CLASS-II; MONOCLONAL-ANTIBODY; IGG4 ANTIBODIES; ANTIGEN; DEATH; MALIGNANCIES; MOLECULES; TRIAL; VIVO Multiple languages Oncology; Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47768