Clinical Trials

Primary Objective: Phase 1: To determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) of SAR650984 (Isatuximab). Phase 2 (stage 1): To evaluate the activity of single-agent Isatuximab at different doses/schedules and to select dose and regimen to further evaluate the overall response rate (ORR) of Isatuximab as single agent or in combination with dexamethasone. Phase 2 (stage 2): To evaluate the activity in terms of overall response rate (ORR) of Isatuximab at the selected dose/schedule from stage1, as single agent (ISA arm) and in combination with dexamethasone (ISAdex arm). Secondary Objectives: Phase 1: - To characterize the global safety profile including cumulative toxicities. - To evaluate the pharmacokinetic (PK) profile of Isatuximab in the proposed dosing schedule(s). - To assess the pharmacodynamics (PD), immune response, and preliminary disease response. Phase 2 (stage 1): to evaluate the following objectives for Isatuximab as single agent: - Safety - Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival. Phase 2 (stage 2): to evaluate the following objectives in each arm (ISA and ISAdex): - Safety - Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival.

The purpose of this study is to answer the important question: Does early treatment with highly effective DMT (Disease Modifying Therapy) improve the prognosis for people with MS? This is an area of significant controversy and no data currently exist to guide treatment choices for patients and clinicians.  

In 1985, the United States Food and Drug Administration (FDA) approved multichannel cochlear implants (CIs) for adults with profound hearing loss; and in 1990, implantation was approved for children. Since then, this procedure has become the standard of care for patients with severe-to-profound sensorineural hearing loss. Successful outcomes are dependent not only on extrinsic factors, but also on intrinsic factors that cannot always be modified by the CI team. Significant predictive factors for hearing outcomes in patients with CIs have been previously reported. These include, but are not limited to, duration of deafness, level of preimplant speech recognition, pre/postlingual status, and the coupling of device electrodes. Recipient age does not appear to have a significant impact on hearing outcomes in elderly candidates.

Earlier studies have found that, because of its dimensions and proximity to the spiral ganglion cells, the scala tympani (ST) is the preferred location for CI electrode placement. A number of recent studies have proposed that intraoperative factors may be important determinants of electrode location and possibly of audiological outcome. Preliminary reports suggest that intracochlear electrode position- specifically, placement within the ST-is associated with improved audiological outcomes. Additionally, different surgical techniques have been proposed to minimize trauma during electrode insertion and to increase the likelihood of placement within the ST - namely round window and anteroinferior cochleostomy electrode insertion.

Currently, the best surgical approach for electrode insertion is highly debated, fueled by a lack of strong evidence to support one method over another. While a number of CI centers have begun to utilize a round window approach, many large volume centers in the United States and world wide continue to routinely employ cochleostomy electrode insertions. With an increasing number of patients being implanted with greater degrees of residual hearing, such data will become critical towards reducing intracochlear injury and optimizing patient outcomes. To the investigators' knowledge, no clinical study has prospectively investigated the relationship between surgical insertion technique, intracochlear electrode location, and postoperative hearing outcomes. To this end, the investigators are initiating a multicenter prospective randomized controlled double-blinded study comparing round window and cochleostomy cochlear implant electrode insertion.

The purpose of this study is to evaluate the safety, tolerability, feasibility, and preliminary effectiveness of the administration of genetically-modified autologous T cells (CART-TnMUC1 cells) engineered to express a chimeric antigen receptor (CAR) capable of recognizing the tumor antigen, TnMUC1 and activating the T cell (CART- TnMUC1 cells).

The purpose of this study is to assess the effect of Reldesemtiv versus placebo on functional outcomes in Amyotrophic Lateral Sclerosis (ALS).

The purpose of this study is to find out which commercially-available activity tracking devices most accurately track steps in both controlled and free-walking conditions.

The purpose of this study is to assess the safety, pharmacokinetics and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI2228 in adult subjects with multiple myeloma who are either transplant ineligible or post autologous stem cell transplant and are relapsed/refractory.

The primary purposes of this study are to identify experimental therapies that improve OS for GBM patients in the Screening stage (Stage 1), determining if predefined patient subtypes or associated biomarkers uniquely benefit from the treatment and to confirm identified effective experimental therapies and associated biomarker signatures in an expansion stage (Stage 2) designed to support a new drug application.

The purpose of this study is primarily designed to evaluate the safety and tolerability of CCS1477 in patients with relapsed or refractory acute myeloid leukaemia (AML)/high-risk myelodysplastic syndrome (MDS), multiple myeloma (MM) and non-Hodgkin lymphoma (NHL; B or T-cell).

CCS1477 is a potent, selective and orally bioavailable inhibitor of the bromodomain of p300 and CBP, critical transcriptional co-activators of genes that drive cell proliferation and survival. The compound causes G1 cell cycle arrest and is anti-proliferative across a broad range of haematological cell models, representative of AML, MM and lymphomas. This is also accompanied by an increase in myeloid differentiation in AML cells. CCS1477 has significant anti-tumour activity as a monotherapy in xenograft models of AML and multiple myeloma.

Additionally, there are molecular features of certain haematological malignancies that are likely to increase the sensitivity to p300/CBP inhibition with CCS1477. For example, in B-cell lymphomas there are frequent loss of function mutations in CBP. These tumours become dependent on the non-mutated p300 paralogue (twin) protein for their continued growth. When p300 is inhibited, this drives synthetic lethality leading to apoptosis/cell death.

This study will determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) and schedule(s) of CCS1477 and investigate clinical activity of CCS1477 monotherapy in patients with haematological malignancies.

RATIONALE: Breast-conserving surgery is a less invasive type of surgery for breast cancer and may have fewer side effects and improve recovery. Radiation therapy uses high-energy x rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial studies how well breast-conserving surgery and radiation therapy work in treating patients with multiple ipsilateral breast cancer