Multiple Myeloma

Aou Citta' Della Salute E Della Scienza Di Torino

Investigate eNAMPT in Multiple Myeloma Biology and Establish Its Role in Disease Progression

INVESTIGATING eNAMPT ROLE IN ACQUISITION OF EPITHELIAL TO MESENCHYMAL TRANSITION-LIKE FEATURES IN MULTIPLE MYELOMA

To strengthen preliminary data and to investigate the correlation between eNAMPT levels in BM and peripheral blood (PB) compartments by assessing its concentration in paired samples collected from a larger cohort of NDMM patients, using also more HDs as control.

To disclose eNAMPT relevance as potential marker of disease progression by comparing eNAMPT plasmatic levels from samples collected in different phases of disease (MGUS, Smoldering Multiple Myeloma -SMM-, NDMM, relapsed/refractory MM) and by their correlation with available clinical data.

To investigate cellular source of eNAMPT production in MM by analyzing both MM cells (Established Human Myeloma Cell Lines, HMCLs and primary CD138+ cells) and MM-BMSC compartment.

To investigate eNAMPT role in EMT features acquisition of HMCLs (with known molecular features such as karyotype status, mutations, drug-resistance phenotype etc.) and to define the underlying molecular mechanisms.

To determine the effects of previously identified neutralizing αeNAMPT antibody (Ab) (13) on MM cells both in vitro and in an in vivo MM-xenografted mouse model.

Dr. Alessandra Larocca

Principal Investigator

University of Turin, Italy

Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.

Chemotherapy-induced Peripheral Neuropathy

Breast Cancer Metastatic

Platinum-resistant Recurrent Ovarian Cancer

Nicotinamide Riboside

University of Iowa Hospitals and Clinics

Wake Forest Baptist Comprehensive Cancer Center

NR in Chemo-induced Peripheral Neuropathy

Nicotinamide Riboside (NR) in Paclitaxel-induced Peripheral Neuropathy

The primary outcome variable is binary (yes/no), and defined as no worsening of the grade of peripheral sensory neuropathy, scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 guidelines.

Quantitate the percentage of patients that experience a dose reduction of paclitaxel or nab-paclitaxel therapy due to neuropathy;

Count the number of (i.e. the incidence) of dose reduction events due to neuropathy (each occasion of dose reduction is a separate event);

Quantitate the total cumulative dose of paclitaxel administered over the 12 weeks.

Score on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity questionnaire. This questionnaire asks 11 questions that are specific to chemotherapy-induced peripheral neuropathies.

Exploratory analysis of ability of the clinical version of the Total Neuropathy Score questionnaire to detect changes in CIPN severity over time. Unlike the CTCAE or the FACT&GOG-NTX questionnaires, the TNS is a patient reported outcome measure.

All of the individual participant data collected during the trial, after de-identification, will be shared with researchers who provide a methodologically sound proposal to achieve aims in the approved proposal. The IPD will be available to sharing immediately after publication and ending 5 years after article publication

Donna Hammond, PhD

Professor

National Cancer Institute (NCI)

ChromaDex, Inc.

All subjects with stage IV breast cancer will receive 300 mg NIAGEN®) daily for one week followed by dose escalation to 1000 mg daily for 11 weeks upon reporting the development of grade 1 sensory neuropathy. Those presenting with a residual sensory neuropathy of ≤ 2 as a result of prior chemotherapy will also be enrolled.

Epirubicin 90 mg/m2 and cyclophosphamide 600mg/m2 IV every 3 weeks for 4 cycles.
Nab paclitaxel 125mg/m2 IV days 1, 8 and 15 for 12 weeks In case of HER2 positive tumour patients will receive trastuzumab in combination with nab-Paclitaxel

Breast Cancer

Nab-Paclitaxel- 125 mg/m2 days 1,8, 15 for 12 weeks

Nab-Paclitaxel

Bankstown Lidcome Hospital

Royal North Shore Hospital

Barwon Health

St John of God Healthcare, Geelong

South West Healthcare

IST Neoadjuvant Abraxane in Newly Diagnosed Breast Cancer

Tailored Neoadjuvant Epirubicin and Cyclophosphamide (EC) and Nanoparticle Albumin Bound (Nab) Paclitaxel for Newly Diagnosed Breast Cancer

Pathological complete response defined as breast only, ypT0/ ypTis regardless of nodal status

Safety will be measured using NCI Common Toxicity Criteria for Adverse Effects version 4.0

nicotinamide/krūties vėžys

Investigate eNAMPT in Multiple Myeloma Biology and Establish Its Role in Disease Progression

NR in Chemo-induced Peripheral Neuropathy

IST Neoadjuvant Abraxane in Newly Diagnosed Breast Cancer

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