NM-IL-12 is being evaluated as an immunotherapeutic with concomitant hematopoietic regenerating properties for treatment of relapsed/refractory DLBCL, an aggressive type of B-cell non-Hodgkin's lymphoma (NHL). Determination of the maximum tolerated dose (MTD) for NM-IL-12 is not planned in this study, rather, a pre-defined dose of 150 ng/kg will be explored; this dose is based on two safety and tolerability studies of NM-IL-12 in healthy volunteers.
This is a single-arm, open-label, non-randomized, multi-center study with NM-IL-12 dosed in combination with salvage chemotherapy regimens (R-ICE = rituximab plus ifosfamide-carboplatin-etoposide, R-DHAP = rituximab plus cytosine arabinoside-cisplatin-dexamethasone) for treatment of patients with relapsed/refractory DLBCL. NM-IL-12 (150 ng/kg) will be administered subcutaneously. Patients will be monitored as routinely practiced; in addition, approximately 1 day after NM-IL-12 injection, patients will have a home visit by a nurse for blood sampling related to pharmacokinetic and pharmacodynamic (PK/PD) evaluation. Twelve patients are planned to be enrolled into the study; initially 6 patients will be enrolled. The decision to continue and recruit the remaining six patients will be made by Data Safety Monitoring Board (DSMB) after review of relevant safety data, clinical laboratory evaluations, and vital signs collected up to 21 days post enrollment of the last patient in the first treated group. Common Terminology Grades for Adverse Events (CTCAE) guidelines will be used to determine dose-modifying criteria (DMC).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Single SC administration of NM-IL-12 will be administered at least 48 hours after completion of the last chemotherapy dose of each cycle
Safety and tolerability
General safety: Vital signs (temperature, blood pressure, pulse rate, respiratory rate) and physical examination. • Toxicity according to the NCI CTCAE (v4.03) for AEs and clinical laboratory profile; AEs will be collected for all patients who received at least one dose of NM-IL-12 and up to one month post last NM-IL-12 dose.
Time frame: 4 months
Immunogenicity of NM-IL-12
Immunogenicity of NM-IL-12 will be evaluated by the presence of anti-drug antibody (ADA)
Time frame: 4 months
Response rate (Complete Response or Partial Response) as assessed by PET/CT
Comparison will be made between the status before salvage regimen initiation, after the second chemotherapy cycle, and after completion of all salvage chemotherapy cycles. CR and PR will be assessed according to the revised International Working Group Criteria for non-Hodgkin Lymphoma.
Time frame: 4 months
Time to neutrophil recovery
Time to neutrophil recovery, as defined by first day of ANC ≥ 500/μL
Time frame: 4 months
Time to platelet count recovery
Time to platelet count recovery, as defined by first day of self-sustained platelet count ≥ 20,000/μL
Time frame: 4 months
Incidence of systemic infections
Time frame: 4 months
Incidence and duration of neutropenic fever
Time frame: 4 months
Need for RBC and platelet transfusion
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Time frame: 4 months
Peak Plasma Concentration (Cmax) of NM-IL-12
Time frame: 2 months
Area under the plasma concentration versus time curve (AUC) of NM-IL-12
Time frame: 2 months
Peak Plasma Concentration (Cmax) of IFN-g and IP-10
Time frame: 2 months