Reference Detail

Ref Type

Journal Article

PMID

(23090290)

Authors

Schweighofer CD, Tuchscherer A, Sperka S, Meyer T, Rattel B, Stein S, Ismail S, Elter T, Staib P, Reiser M, Hallek M

Title

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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer immunology, immunotherapy : CII	61	12	2012 Dec	2367-73	Cancer Immunol Immunother

URL

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
ID09C3	ID09C3	0	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
ID09C3				ID09C3 is a human monoclonal IgG4-type antibody targeting HLA-DR and may result in apoptotic activity in lymphoma tumors (PMID: 23090290).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References