Primary trial objective in this three arm trial is to assess the safety and tolerability of EMD 521873, and to determine whether the maximum tolerated dose (MTD) is reached with EMD 521873 doses of up to 1.5 mg/kg given alone or in combination with fixed, low-dose cyclophosphamide (CPA) in patients with metastatic or locally advanced solid tumors or B-cell non-Hodgkin lymphoma. Secondary objectives are to evaluate pharmacokinetic, immunogenicity, overall and best clinical response, changes in tumor marker levels, survival and biological/immune responses to EMD 521873. A total of 78 patients are planned. Patients will remain on the dose throughout the trial. It is intended to administer 3 cycles (21 d each, or until progression or a xxx line therapy becomes necessary.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Dose escalation steps: Group 1: 0,075mg/kg - 0,15mg/kg - 0,225mg/kg - 0,3mg/kg - 0,45mg/kg - 0,6mg/kg - 0,9mg/kg (-1,8mg/kg - 2,1mg/kg - 2,5mg/kg - 3,0mg/kg) Disease control and decision of continuation in patient who benefit from the treatment: Every second cycle
Dose escalation steps: Group 2: CPA plus 0,6mg/kg - 0,9mg/kg Disease control and decision of continuation in patient who benefit from the treatment: Every second cycle
Dose escalation steps: Group 3: 0,9mg/kg - 1,2mg/kg - 1,5mg/kg (-1,8mg/kg - 2,1mg/kg - 2,5mg/kg - 3,0mg/kg) Disease control and decision of continuation in patient who benefit from the treatment: Every second cycle
Universitäts-Klinikum Mainz III.Medizinische Klinik
Mainz, Germany
Medizinische Klinik Universitätsklinikum Mannheim Medizinische Fakultät Mannheim
Mannheim, Germany
Istituto Oncologico della Svizzera Italiana Ospedale Regionale Bellinzona e Valli (IOSI)
Bellinzona, Switzerland
University of Lausanne Hospitals (CHUV) and Hospitals of Riveria-Chablais
Lausanne, Switzerland
Kantonsspital St. Gallen
Sankt Gallen, Switzerland
Assess the safety and tolerability of EMD 521873
Time frame: First administration of any dose of EMD521873 until last administration plus 30 days.
To determine whether the MTD is reached with EMD 521873 doses of up to 1.5 mg/kg given alone or in combination with fixed, low-dose CPA in patients with metastatic or locally advanced solid tumors or B-cell non-Hodgkin lymphoma
Time frame: Incidence of DLTs occurring during the first cycle of administration of any dose of EMD 521873 given alone on 3 times per cycle (group 1) or with fixed low-dose CPA plus EMD 521873 (group 2) or of EMD 521873 given alone on once per cycle (group 3).
Characterize the PK profile of EMD 521873 alone or in combination with fixed lowdose CPA
Time frame: Cycle 1-3 of EMD 521873 treatment
Evaluate the immunogenicity of EMD 521873 alone or in combination with CPA measured by the induction of o Specific antibodies against the genetically modified IL-2 o Fc-IL2-specific antibodies o Anti-idiotype antibodies
Time frame: Every EMD 521873 treatment cycle
Collect evidence of best overall response, changes in serum tumor marker levels and best clinical response after treatment with EMD 521873 alone or in combination with CPA
Time frame: Every second EMD 521873 treatment cycle
Evaluate survival
Time frame: Until 1 year after the last patient received his last dose of EMD 521873
Evaluate biological responses to EMD 521873 alone or in combination with CPA as measured by o Absolute cell numbers and ratios of lymphocyte subsets in defined combinations o Change in serum level of sIL2R and neopterin
Time frame: Cycle 1-3 of EMD 521873 treatment
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