Dual Mobility Acetabular Cups in Revision TJA
The aim of this study is to the compare clinical outcomes of patients undergoing a revision
total hip arthroplasty (THA) with the use of a dual mobility bearing versus a single bearing
design with the use of a large femoral head (36mm or 40mm). We hypothesize the use of
dual-mobility components in revision THA will be associated with a lower dislocation rate in
the first year following surgery.
Portico Re-sheathable Transcatheter Aortic Valve System US IDE Trial
The PORTICO pivotal IDE trial will include a randomized cohort of 750 subjects enrolled at up
to 70 investigational sites in the United States and Australia. Patients will be randomized
(1:1) to receive the SJM Portico Transcatheter Heart Valve and Delivery Systems (Portico) or
any FDA-approved, commercially-available Transcatheter Aortic Valve Replacement (TAVR)
System. The randomized cohort will be tested for two co-primary endpoints at 30 days (primary
safety endpoint) and 1 year (primary effectiveness endpoint). At the time of the primary
randomized cohort analysis, the risk cohorts will be combined and analysis will be conducted
on the intention-to-treat (n=750) population.
The FlexNav Delivery System study will be conducted as a separate arm of the PORTICO IDE
trial and will include up to 200 high or extreme risk subjects; including a minimum of 100
analysis subjects. The study will characterize the safety of the next-generation Portico
Delivery System ("FlexNav™ Delivery System"). The primary analysis cohort will include
FlexNav analysis subjects.
The IDE Valve-in-Valve registry will enroll up to 100 high or extreme risk subjects with a
failed surgical bioprosthesis who are eligible to receive a Portico Transcatheter Heart
Valve.
All subjects enrolled in the PORTICO pivotal IDE trial will undergo follow-up at baseline,
peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30
days, 6 months, 12-months and then annually through 5-years.
Dual-mobility vs. Single-bearing Components in THA at "High Risk" for Prosthetic Dislocation
This study aims to compare the clinical outcomes of patients considered to be at high risk
for prosthetic dislocation undergoing primary total hip arthroplasty (THA) with the use of a
dual mobility bearing versus a conventional, single-bearing design.
We hypothesize that in primary THA patients considered to be at high risk for prosthetic
dislocation, the use of dual-mobility components will be associated with a lower dislocation
rate in the first year following the index procedure. We do not anticipate a difference. In
other clinical outcome measures or functional outcome scores between the two cohorts.
Study Design: Randomized controlled trial with two groups: THA with dual mobility.
44 components vs THA with single-bearing designs
Protocol for Immunology Specimen Collection From Cancer Patients, Patients With Hematologic Diagnoses, and Healthy Normal Controls
PRIMARY OBJECTIVES; I. Identify changes in immune system parameters in patients receiving
immunotherapies (including immune checkpoint inhibitors, immunostimulatory/immunomodulatory
agents, cellular therapies, stem cell transplantation) and compare to changes in patients
receiving conventional chemotherapy, targeted-agent therapy, and healthy normal volunteers
using multiparameter flow cytometry, time-of-flight mass cytometry, cytokine quantification,
functional analysis of immune cell subsets isolated via fluorescence activated cell sorting
(FACS), and genetic and proteomic techniques (deoxyribonucleic acid [DNA] sequencing,
ribonucleic acid sequence [RNASeq], reverse transcriptase-polymerase chain reaction [RT-PCR],
Western blot).
SECONDARY OBJECTIVES:
I. Optimize methods for measuring functional status of circulating immune cells and
hematopoietic progenitors (activation, inhibition, cytotoxicity, proliferative capacity).
II. Use genetic and epigenetic techniques to a) study clonal diversity in T cell subsets b)
determine the genetic basis for T cell immune reconstitution following stem cell
transplantation.
OUTLINE:
Patients and healthy normal volunteers undergo collection of peripheral blood samples for
analysis via flow cytometry, RNASeq, immunohistochemistry, cytometry by time of flight
(CyTOF) experiments, cell cultures, and functional studies of immune cell subsets obtained by
FACS. Patients also undergo collection of bone marrow and leukopheresis/leukoreduction
specimens, and single cell suspensions and bulk excised tumor biopsies are obtained from
routine testing for analysis via immunohistochemistry or CyTOF.
After completion of study, patients are followed up for up to 2 years.
Establishing a Diagnosis of Lung Cancer Through a Fluid Biopsy
PRIMARY OBJECTIVE:
I. To estimate the sensitivity and specificity of the fluid biopsy in establishing a
diagnosis of bronchogenic carcinoma.
SECONDARY OBJECTIVES:
I. To determine the accuracy of determination of the histologic subtype of bronchogenic lung
cancer.
II. To determine the relative contribution of cell based high definition circulating tumor
cell assay (HD-CTC) and imaging mass cytometry (IMC) and plasma based circulating tumor
deoxyribonucleic acid (ctDNA) assays in determination of diagnosis and histologic subtype.
OUTLINE:
Patients undergo collection of blood samples on day 1 for analysis via high definition
(HD)-single cell analysis (SCA) fluid biopsy. Medical charts of patients are reviewed at 3
months post-biopsy or computed tomography (CT) screening.
After completion of study, patients are followed for up to 1 year.
Phase 1/2 Dose Escalation and Cohort Expansion Study Evaluating MCLA-158 (Petosemtamab) as Single Agent or in Combination in Advanced Solid Tumors
Study Design:
This open label, multicenter, first-in-human study consists of 2 parts. Part 1 is a dose
escalation to find the recommended Phase II dose (RP2D) of MCLA-158 studying patients with
metastatic colorectal cancer. Enrollment in the dose escalation part has been completed.
Dose expansion (single-agent cohorts) In an expansion part of the study, the activity,
safety, and tolerability of MCLA-158 at 1500 mg every 2 weeks (Q2W) (preliminary RP2D) as a
single agent will be evaluated in cohorts of selected solid tumor indications with dependency
on EGFR signaling. Eligible solid tumor indications may include locally advanced unresectable
or metastatic HNSCC, gastric/gastroesophageal junction adenocarcinoma (GEA) with EGFR
amplification and/or high EGFR expression, esophageal carcinoma and pancreatic
adenocarcinoma. Additionally, safety will be characterized at two dose levels in this
setting.
Dose expansion (in combination with pembrolizumab cohort)
MCLA-158 in combination with pembrolizumab will be explored first in HNSCC patients eligible
to receive pembrolizumab as first-line monotherapy. Other expansion cohorts may be considered
for combination treatment in the future.
Norris ORIEN Total Cancer Care Protocol: A Lifetime Partnership With Patients
PRIMARY OBJECTIVES:
I. To establish a longitudinal study of clinical and related data from patients with or at
risk for cancer.
II. To establish a large biospecimen repository that is linked to clinical and related data.
III. To follow patients through their lifetime though passive or active follow-up.
IV. To use clinical data, tissues, other biological samples and derived molecular data in the
Total Cancer Care Protocol (TCCP) repositories to match patients in this TCCP study to future
studies.
OUTLINE:
Patients undergo collection of blood during a regular care visit or not up to 4 times a year.
Extra tissue is collected after removal during standard of care surgery and patients may
undergo additional tumor sampling (needle passes) at the time of planned diagnostic biopsies.
During bone marrow biopsy, the doctor may reposition the needle up to 3 times, and bone
marrow for research will not be collected more than 4 times per year. Patients may undergo
additional collection of other biological samples such as saliva, sputum, urine, feces, hair,
and surface skin swabs for analysis. Patients also receive surveys or questionnaires to
collect demographics, medical, family, and nutritional history, cancer predisposing risk
factors, quality of life data, and quality of care data.
After completion of study, patients are followed up periodically.
Characterization of T-cell Repertoire in Patients With AML Undergoing HSCT Through Next-Generation Sequencing of T Cell Receptor Alpha (TCRA) and T Cell Receptor Beta (TCRB) Genes
PRIMARY OBJECTIVES:
I. Characterize the T cell receptor (TCR) repertoire in acute myeloid leukemia (AML) patients
before and after receiving hematologic stem cell transplantation (HSCT).
II. Identify molecular changes (germline variants and somatic mutations) that contribute to
shaping the TCR repertoire.
OUTLINE:
Patents undergo collection of blood samples before, on day 100, and 1 year after HSCT. Donors
undergo collection of blood at the time of HSCT for ribonucleic acid (RNA)-based next
generation sequencing of TCRA and TCRB genes.
Surveillance Monitoring for ART Toxicities Study in HIV Uninfected Children Born to HIV Infected Women
Many antiretroviral therapy (ART) medications given to a pregnant woman cross the placenta
and can be detected in the amniotic fluid and cord blood resulting in substantial fetal
exposure. Therefore, there is concern about toxicity of the drugs in the fetus and infant. It
is noteworthy that none of the currently approved ART medications for the prevention of
maternal to fetal transmission of HIV are in Food and Drug Administration (FDA) Pregnancy
Category A (no fetal risk ascertained in adequately controlled human studies). Thus, there is
continued need to examine the toxicity of ART in HIV transmission prevention for the
short-term toxicity of newer agents and combinations as well as the unanswered questions of
longer term toxicity and subtle adverse effects.
The study will use a registry approach to conduct active surveillance among children < 12
years of age at enrollment. Occurrences of abnormalities from ART exposure in utero and/or in
the first two months of life will be sought in multiple domains, including metabolic, growth,
cardiac, neurologic, neurodevelopmental, behavior, language, and hearing. Clinical and
laboratory data will be examined for abnormalities through a hierarchy of evaluations:
adverse events (AE) will be identified → selected AEs will trigger predefined additional
evaluations → significant observations will be defined as cases → a pattern of significant
study-wide cases will be defined as signals. The incidence of these events of interest will
be monitored over time and by ART regimen, and compared with historical data that may be
suggestive of a signal. Some signals may be testable using existing and/or previously
collected data, while other signals may indicate the need for additional hypothesis-driven
studies outside of SMARTT.
The objectives of SMARTT are:
1. To estimate the occurrence of potential ART-related toxicities through an ongoing
surveillance system among HIV-uninfected children born to mothers with HIV infection
with and without exposure to ART in utero and/or in the first two months of life and
compare the occurrences of these outcomes with other sources of data as well as by ART
exposures; and
2. To actively encourage hypothesis-driven studies to confirm that the signals are due to
ART exposure in utero and/or in the first two months of life. Note that the full design
and execution of these studies may be beyond the scope of the SMARTT study but will be
facilitated by SMARTT.
The specific aims of SMARTT are:
1. To create a Static Surveillance Cohort to extend domain-specific data collection in
children either 1) previously enrolled in any of the approved studies for enrollment
into SMARTT; 2) previously enrolled in another pediatric HIV/AIDS cohort study with
SMARTT Protocol Chair approval, or 3) not previously enrolled in an approved study but
with equivalent data available in the medical record;
2. To create a Dynamic Surveillance Cohort to examine domain-specific data of children
newly exposed to ART in utero and/or in the first two months of life;
3. To create a Young Adult Cohort to study long-term outcomes in SMARTT participants
formerly enrolled in the Static and Dynamic cohorts.
4. To identify a set of "triggers" for each domain that define a "signal" of possible ART
toxicity and compare the occurrence of these signals with previously collected data and
by ART exposure; and
5. To encourage and facilitate the development of hypothesis-driven studies to evaluate
whether a "signal" is the result of ART exposure in utero and/or in the first two months
of life.
Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor
AFNT-211 is a cellular therapy consisting of autologous CD4+ and CD8+ T cells engineered to
express a human leukocyte antigen-A (HLA-A)*11:01-restricted Kirsten rat sarcoma (KRAS)
G12V-specific transgenic T cell receptor (TCR), the wildtype CD8α/β coreceptor, and a
FAS-41BB switch receptor. AFNT-211 is being developed by Affini-T Therapeutics, Inc.
(hereafter, "the Sponsor") for the treatment of patients with malignant solid tumors. The
primary purpose of this study is to assess the safety and tolerability of AFNT-211 in
subjects who are HLA-A*11:01 positive with advanced or metastatic cancers that harbor a KRAS
G12V mutation, as well as determine the optimal biological dose (OBD) and recommended Phase
II dose (RP2D) of AFNT-211 in this population. This study will also evaluate the preliminary
anti-tumor activity of AFNT-211.
Metabolic Profiling of Peripheral Blood Mononuclear Cells (PBMCs) by LC-MS in Prostate Cancer Patients
PRIMARY OBJECTIVES:
I. Develop blood sample collection and preparation procedures for reliable, meaningful
metabolomic profiling of peripheral blood mononuclear cells (PBMCs) by liquid
chromatography/quadruple-time of flight/mass spectrometry (LC/Q-TOF/MS) that can be
implemented in a clinical setting.
II. Optimize data analysis methods and software usage to create a metabolic profile for
patients at the time of blood collection.
III. Compare metabolite profiles of isolated PBMCs versus (vs.) other blood fractions
(plasma, red blood cells [RBCs], and whole blood).
IV. Identify elements of the PBMC metabolite profile that may correlate to patient disease
state.
OUTLINE:
Patients undergo collection of blood for metabolic profiling via LC/Q-TOF/MS.
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