CD Flex: An Open-Label, Non-Inferiority Study Evaluating the Efficacy and Safety of Two Injection Schedules of Xeomin (incobotulinumtoxinA) [Short Flex vs. Long Flex] in Subjects with Cervical Dystonia with < 10 Weeks of Benefit from OnabotulinumtoxinA Treatment MUS 60201 4073 1
Dystonia is a movement disorder characterized by sustained, involuntary muscle contractions which frequently causes twisting and repetitive movements or abnormal postures. Cervical dystonia (CD) is the most commonly described form of focal dystonia (abnormality involving a single area of the body). Xeomin (botulinum toxin type A), the study drug, has been shown to be effective and safe in the treatment of CD with two Phase III trials. Current practice in the treatment of CD with onabotulinumtoxinA (Botox) injection is to inject patients every 3 months. However, not all patients receive benefit from injections for the duration of 3 months. This study is designed to examine a shorter treatment interval with Xeomin injections and compare to the standard interval to determine if there is a difference from an efficacy standpoint (i.e., do the patients receive continuous benefit versus peaks and valleys) and if more frequent dosing leads to more development of botulinum toxin resistance. This study will evaluate if shorter dosing intervals is non-inferior to standard or longer dosing intervals by using the Toronto Western Spasmodic Torticollis Scale (TWSTRS) at control Visit 4 weeks post the the 8th injection. Secondary outcomes will evaluate efficacy, onset and offste of efficacy, safety and immunology. The primary efficacy variable will be defined as the change from study entry baseline in the TWSTRS-Severity score assessed at the 4-week control visti after the 8th injection (PPS sample). An analysis of covariance (ANCOVA) will be used for the primary efficacy analysis. All analysis of secondary endpoints for efficacy will be considered exploratory.
Proleukin Observational Registry to Evaluate the Treatment Patterns and Clinical Response in Malignancy
The PROCLAIM Registry is a US-based, multicenter Registry designed to establish a high
quality observational database of real-world clinical data on HD IL-2 when used to treat
patients with mRCC, mM or other malignancies. The Registry will not, in any way, suggest
changes in the treatment or management of the patients enrolled in the Registry. Therefore,
physicians will continue to manage and treat patients according to standard of care and their
own judgment.
The PROCLAIM Registry will start with a retrospective pilot data collection from a
de-identified finite number of patient cases abstracted from their existing medical charts.
The features collected will be identical to those planned for the prospective registry. The
resulting database will be used to formulate hypotheses to be tested using the prospective
registry database. Patients utilized in the retrospective analysis will be excluded from the
prospective portion of the Registry.
In the prospective portion of the Registry, sites will enroll patients who are expected to
start a course of HD IL-2 therapy. Once enrolled, the patient must receive at least one dose
of HD IL-2 to remain in the Registry. Patients will be treated and followed according to the
site's standard of care. This Registry will in no way induce changes in the management of
individual patients. Clinical data features will be entered into an Electronic Data Capture
(EDC) system, and organized into a registry database.
The data contained in the registry database will be observational data. The PROCLAIM Registry
does not stipulate patient care, specific visits or interventions but merely surveys
standardized parameters regarding HD IL-2 and associated therapies as they are applied by
treatment centers. The collection of standard data over time permits the evaluation of trends
in patient survival and subsequent therapy exposure. The database will be used to answer
future queries formulated by researchers.
A 12-month, Randomized, Rater- and Dose-blinded Study to Compare the Efficacy and Safety of Fingolimod 0.25 mg and 0.5 mg Administered Orally Once Daily With Glatiramer Acetate 20 mg Administered Subcutaneously Once Daily in Patients With Relapsing-remitting Multiple Sclerosis
This was a multicenter, randomized, rater- and dose-blinded, study to compare the efficacy
and safety of 0.25 mg and 0.5 mg of fingolimod with glatimer acetate 20 mg s.c. in patients
with RRMS.
This study consisted of 3 periods:
- Screening Period: up to 45 days for all patients
- Treatment Period: 12 months of glatiramer acetate 20 mg, fingolimod 0.25 mg, or
fingolimod 0.5 mg
- Follow-up occurred 3 months (12 weeks) after the last dose of study drug for all
patients The informed consent form was signed prior to any study related activities at
the screening visit. Randomization to either treatment group was preformed at visit 1
after a diligent check of applicable in- and exclusion criteria in a 1:1:1 ratio
(changed to 5:3:2 after implementation of Amendment 2 in 2015).
Treatment groups:
- fingolimod 0.5 mg/day orally for up to 12 months
- fingolimod 0.25 mg/day orally for up to 12 months
- glatiramer acetate 20 mg/day subcutaneously for up to 12 months
4P-12-1 A Randomized Phase II Trial of Dasatinib plus Abiraterone Compared to Abiraterone Alone for Metastatic, Castration-Resistant Prostate Cancer Prior to Chemotherapy
PRIMARY OBJECTIVES:
I. To compare the progression-free survival of men with metastatic castration-resistant
prostate cancer treated with abiraterone (abiraterone acetate) plus dasatinib to that of men
treated with abiraterone alone.
SECONDARY OBJECTIVES:
I. To describe the toxicity profile of the combination, as well as the rate of
prostate-specific antigen (PSA) response, objective responses, and changes in circulating
tumor cell (CTC) numbers.
OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive
abiraterone acetate 1000 mg orally (PO) once daily (QD) and prednisone 5 mg PO twice daily
(BID) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or
unacceptable toxicity.
ARM B: Patients receive abiraterone acetate and prednisone as patients in arm A. Patients
also receive dasatinib 100 mg PO QD on days 1-28. Courses repeat every 4 weeks in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Randomized Trial of Pegylated Interferon Alfa-2a Versus Hydroxyurea Therapy in the Treatment of High Risk Polycythemia Vera (PV) and High Risk Essential Thrombocythemia (ET)
The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are a group of clonal
hematological malignancies that are characterized by a chronic course which can be punctuated
by a number of disease related events including thrombosis, hemorrhage, pruritis and leukemic
transformation. These disorders include Polycythemia Vera (PV), Essential Thrombocythemia
(ET) and Primary Myelofibrosis (PM). Recently an acquired somatic mutation in the
intracellular kinase, JAK2 (JAK2V617F) has been observed in 95% of patients with PV, 50% of
patients with ET and 50% of patients with primary myelofibrosis. At present the
chemotherapeutic agent hydroxyurea is the standard of care for high risk patients with PV.
Concern exists about prolonged use of this drug leading to leukemia and the inability of
hydroxyurea to eliminate the malignant clone.
Interferon (rIFN -2b), is a drug that appears to be non-leukemogenic, and may have a
preferential activity on the malignant clone in PV, as suggested by cytogenetic remissions
obtained in patients treated with rIFN -2b. Several investigators recently reported that
patients with PV treated with rIFN -2b had lower JAK2V617F allele burdens as compared to a
control group that included patients treated with phlebotomy, hydroxyurea, or anagrelide, or
who remained untreated. The results confirm the hypothesis that rIFN -2b preferentially
targets the malignant clone in PV and raises the possibility that the JAK2V617F allele
burden, and a reversion of clonal hematopoiesis monitored in females by expression of
X-chromosome polymorphic alleles maybe useful in monitoring minimal residual disease in PV
patients.
Pegylated Interferon Alfa-2a (PEGASYS) has been demonstrated in phase II trials of patients
with PV and ET to have clinical efficacy as measured by normalization of myeloproliferation,
lack of vascular events while on therapy, and a decrease in the JAK2V617F allele burden.
Overall the tolerability of the therapy was good, with each of these trials having a dropout
rate secondary to toxicity of less than 10% of those enrolled. Although dropout rates for
toxicity were low, that is not to say the therapy was without symptomatic toxicity, and
indeed a spectrum of toxicities might be encountered and need to be weighed in the analysis
of the net clinical benefit patients experience on a clinical trial with Pegylated Interferon
Alfa-2a.
A new MPN assessment form will be utilized in this study. This 19 item instrument includes a
previously validated 9 item brief fatigue inventory (BFI), symptoms related to splenomegaly,
inactivity, cough, night sweats, pruritus, bone pains, fevers, weight loss, and an overall
quality of life assessment. The instrument yields an independent result for each symptom
(fatigue is a composite score), as this methodology (of linear analog scale assessment
[LASA]) has proven very valid in the past. This instrument was validated prospectively (by
comparison to a panel of instruments each containing an aspect of the MPN-SAF) for
administration at a single time point.
This is a randomized trial between hydroxyurea and Pegylated Interferon Alfa-2a, it is an
open label clinical trial in two independent disease strata: (1) high risk polycythemia vera
and (2) high risk essential thrombocythemia.
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