Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Ponatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Ponatinib at a dose of 45 mg orally, once daily. If a dose is missed or vomited, the next dose should not be increased to account for missing a dose. Total duration of therapy 3 to 5 years.

Ponatinib at a dose of 30 mg orally, once daily. If a dose is missed or vomited, the next dose should not be increased to account for missing a dose. Total duration of therapy 3 to 5 years.

Starting dose: 45 mg by mouth once daily.

Jorge Cortes, MD

The goal of this clinical research study is to learn if ponatinib can help to control Chronic Myeloid Leukemia (CML) in accelerated phase. The safety of this drug will also be studied.

Ponatinib is designed to block the function of BCR-ABL, which is the abnormal protein responsible for causing leukemia in certain cells.

Ponatinib may cause a blood clot to form in an artery or in a vein. Depending on the location of the clot, this could cause a heart attack, a stroke, severe damage to other tissue, or death. A blood clot may occur within 2 weeks after you start taking the drug. About 25% (1 in 4) of patients taking the drug form an abnormal clot. Blood clots can occur in patients that do not have other known risk factors for forming clots. If you develop a blood clot, you will need to stop taking ponatinib. In some cases, emergency surgery could be needed to remove the clot and restore blood flow.

Study Drug Administration:

You will take ponatinib by mouth 1 time every day while you are on study with about a cup (8 ounces) of water. You should not eat within 2 hours before or after taking the drug. You will complete a study diary in which you will record the date and time that you take the study drug each time. If you miss any doses, you will also note this in the study diary. Bring this diary to every study visit, as described below.

Study Visits:

The tests and procedures for this study have a wide range of time in which they can be done. In general, your schedule of study visits will be as follows:

* Weekly in Month 1
* Monthly in Year 1
* Three (3) to 4 times in Year 2
* Two (2) to 3 times in every year after that

The study staff will help you schedule your study visits. The following tests and procedures will be performed:

* Every 1-2 weeks for the first 4 weeks, then every 4-6 weeks for the first year, then every 3-4 months for the next year, then every 4-6 months after that, blood (about 1/2 tablespoon) will be drawn for routine tests.
* Every 3 months for the first year, you will have an ECG.
* Every 3 months for the first year, then every 6-12 months after that, you will have a physical exam.
* Every 3-4 months for the first year, then every 6-12 months after that, blood (about 2 teaspoons) will be drawn to measure levels of leukemia cells in your body.
* Every 3-4 months for the first year, then every 6-12 months for the next 2 years, then every 2-3 years after that, you will have a bone marrow aspirate for genetic testing and to check the status of the disease.

Length of Participation:

You may continue taking the study drug for up to 5 years. You will be taken off study early if intolerable side effects occur, if the disease gets worse, or if you are unable to follow study directions.

Your participation on the study will be over when you have completed the follow-up visit/call.

Follow-Up:

If you leave the study, you will be called or you will come to the clinic within 30 days to learn about any side effects or symptoms you may be having. If you are called, this call will last about 2-3 minutes.

This is an investigational study. Ponatinib is FDA approved to treat patients with certain types of leukemia. Its use in this study is investigational.

Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.

Participants enrolled before July 25, 2013 were given a starting dose of 45 mg per day. The study was amended and the dose was lowered due to tolerability. Participants enrolled after this date were given a starting dose of 30 mg per day.

Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)

Ponatinib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Accelerated Phase

Proportion of participants with previously-untreated accelerated phase CML attaining complete cytogenetic response (CCyR) at 6 months of treatment with Ponatinib classified according to suppression of the Philadelphia chromosome (Ph) by cytogenetics (FISH if cytogenetic analysis not informative, e.g., insufficient metaphases). CCyR defined as Ph positive 0%.

Proportion of participants with previously-untreated accelerated phase CML receiving treatment of Ponatinib achieving a Complete cytogenetic response (CCyR). Classified according to suppression of the Philadelphia chromosome (Ph) by cytogenetics (FISH if cytogenetic analysis not informative, e.g., insufficient metaphases. CCyR is defined as Ph positive 0%.

Time to toxicity monitoring defined as any grade 3 or 4 drug-related non-hematologic adverse event that has not resolved to grade 2 or less after 6 weeks of optimal therapeutic management, or drug-related toxicity of any grade that in the opinion of the investigator prevents further therapy with ponatinib. Time to toxicity monitored using the Bayesian method of Thall, et al.

Ariad Pharmaceuticals

M.D. Anderson Cancer Center

Ponatinib 45 mg

Ponatinib 30 mg

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Jorge Cortes, MD/Professor, Leukemia

Ponatinib 45 mg orally, once daily. Dose escalation to 30 mg possible for participants with adverse events.

Ponatinib 30mg orally, once daily. Dose escalation to 30 mg possible for participants with adverse events.

Number of Participants With Complete Cytogenetic Response (CCyR)

Elevated Amylase

Lipase Elevation

Pancreatitis

Abdominal Pain

Hypertension

Elevated alanine aminotransferase (ALT)

One participant was not included in analysis.

Toxicity Profile: Most Common Grade 3-4 Non-Hematologic Adverse Events (AEs) Seen in More Than 1 Participant

Overall Study

Heart and Blood Diseases

Coronary Artery Disease

Coronary Disease

Myocardial Ischemia

Ischemia

Heart Diseases

Arteriosclerosis

Arterial Occlusive Diseases

Vascular Diseases

Research PET-MR imaging on Biograph mMR scanner will be conducted immediately following administration of FDG for clinically approved scan. No additional radioisotope will be administered for the research scan.

Participants will undergo research MR-only imaging on Biograph mMR scanner.

Participants will undergo research MR imaging on the Siemens MR scanner

Participants will undergo PET-MR imaging on the Biograph mMR scanner to evaluate the technical aspects of the total acquisition protocol directly post clinical administration of FDG, thus removing the requirement for additional radioisotope.

PET-MR imaging on Biograph mMR scanner

Participants will undergo MR-only imaging to test the technical aspects of the MR-only protocol on the Biograph mMR scanner. No drug administered.

MR-only imaging on Biograph mMR scanner

Participants will undergo MR imaging to test the technical aspects of the MR protocol on the Vida MR scanner

MR imaging on the Siemens Vida 3T MR scanner

Daniel S. Berman, M.D.

Rhona Littman

This is a protocol to facilitate on-site calibration of the technical aspects of the Siemens Biograph mMR (molecular MR) Positron Emission Tomography-Magnetic Resonance (PET-MR) scanner and the 3T Siemens Vida MR scanner at the Cedars-Sinai Medical Center (CSMC) Biomedical Imaging Research Institute (BIRI) Research Imaging Core after scanner installation. The mMR is a FDA-approved standard clinical device (non-experimental) and will be used in accordance with clearance and approval from the FDA. The Vida is a state-of-the-art FDA approved scanner and will be clinically licensed within a short time.

PET-MR Protocol on the Biograph mMR: This protocol requires the use of a radioisotope. To avoid administering radioisotope solely for the purposes of this calibration, we will recruit 20 patients from the clinical population at the S. Mark Taper Foundation Imaging Center at CSMC who are already receiving an isotope dose for their standard-of-care examination and are willing to be scanned at the Research Imaging Core on the same day right after their clinical exam. Subjects who are having a PET-MR after receiving FDG will have the same body part scanned as they did for clinical testing.

MR-only Protocol on the Biograph mMR:To set up MR-only protocols, we will enroll 20 volunteers for MR-only on the mMR scanner. This is a standard MR scan with no isotope involved. Those volunteers who are participating in the MR-only scan will have major body parts and organs scanned as needed for calibration.

MR imaging on the Siemens Vida 3T scanner: applications training is taking place and we will build clinical protocols in the future

Calibration of MR and PET-MR Imaging Protocols at RIC

Calibration of MR and PET-MR Imaging Protocols at the Cedars-Sinai Medical Center (CSMC) Biomedical Imaging Research Institute (BIRI) Research Imaging Core

The mMR is a FDA-approved standard clinical device (non-experimental) and will be used in accordance with clearance and approval from the FDA. Results obtained from these tests will not be analyzed towards the end point of any study and will solely be used to finalize and calibrate the technical performance of the new scanner. All scans will be visually assessed for technique calibration.

Cedars-Sinai Medical Center

Principal Investigator/Chief Cardiac Imaging/Nuclear Cardiology

Asciminib

Patients will receive asciminib (40 mg BID continuous)

Patients will receive best available therapy chosen by investigator

Asciminib comes in 20 mg and 40 mg tablets and is taken orally twice daily

asciminib

Best available treatment will be based on investigator's choice identified prior to randomization. Dose and frequency will depend on label and institutional guidelines for various BAT

best available treatment

Novartis Pharmaceuticals

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of asciminib versus best available therapy in Chinese patients with Chronic Myelogenous Leukemia in chronic phase, previously treated with 2 or more tyrosine kinase inhibitors to support related indication registration in China.

The primary objective of the study is to evaluate the Major Molecular Response (MMR) rate of asciminib treatment at 24 weeks.

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of asciminib versus best available therapy (BAT) in Chinese patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) to support related indication registration in China.

This study will enroll the participants 1) who failed their most recent TKI therapy by meeting the definition of treatment failure as per the 2013 European Leukemia Net (ELN) guidelines, or 2) who were intolerant to the most recent TKI therapy and must have BCR-ABL1 ratio \> 0.1% IS at screening.

Eligible participants will be randomized into asciminib arm or the BAT arm on a 2:1 ratio, to receive asciminib treatment (continuous 40 mg BID) or BAT from Day 1 until the end of study treatment period defined as 96 weeks after the last participant receives the first dose.

Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors

A Randomized, Open-label, Multi-center, Phase II Study of Asciminib Versus Best Available Therapy in Chinese Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Evaluate the major molecular response rate at 24 weeks in asciminib arm

Evaluate the cytogenetic response rate (Complete, Partial, Major, Minor, Minimal, no response) at and by all scheduled data collection time points including 24, 48 and 96 weeks for both asciminib arm and best available treatment arm.

Evaluate the major molecular response rate at week 24 of best available treatment arm, and compare with asciminib arm

Evaluate the major molecular response rate, collected at all scheduled data collection time point (except week 24)

Evaluate the major molecular rate by all scheduled data collection time points including 24, 48 and 96 weeks by treatment group

Evaluate the time from the date of the first dose of study drug to the date of the first documented MMR by treatment group

First document major molecular response to loss of MMR up to 96 weeks after last participant receive the first dose

To evaluate the time from the date of randomization to the date of death (including the survival follow-up period)

Evaluate the time from the date of randomization to the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause (including progressions and deaths observed during the survival follow-up period)

Characterize PK of asciminib in the Chinese CML-CP population. Cmax is the maximum (peak) observed plasma drug concentration after dose administration (ng/mL).

Characterize PK of asciminib in the Chinese CML-CP population. Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (hr).

Characterize PK of asciminib in the Chinese CML-CP population. Trough plasma concentrations (Ctrough)

Characterize PK of asciminib in the Chinese CML-CP population. The partial area under the plasma concentration-time curve from dose time to tau (ng\*hr/mL). For a bid regimen, Tau=12h.

Characterize PK of asciminib in the Chinese CML-CP population. AUClast is the The AUC from the time of dosing to the time of the last measurable plasma concentration (Tlast) (ng\*hr/mL)

Digestive System Diseases

Colorectal Neoplasms

Colonic Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Herbal and Botanical

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Cola

Dose Escalation: To find the dose of regorafenib that can be safely given with nivolumab in patients with advanced, refractory colorectal cancers.

Dose Expansion: To find the effect on tumor of the combination of regorafenib and nivolumab.

Regorafenib orally 80 mg daily for 21 days (3 weeks on, 1 week off).

Regorafenib

Nivolumab 240 mg administered intravenously every 2 weeks.

Dae W Kim, MD

The main purpose of this study is to test the safety, tolerable side effects, and determine the highest tolerable dose of the combination of Regorafenib and Nivolumab. Researchers want to find out if this combination of Regorafenib and Nivolumab can help people with metastatic colorectal cancer with mismatch repair (MMR) proficiency.

Regorafenib and Nivolumab in Mismatch Repair (MMR) Refractory Colorectal Cancer

Phase I Study of Regorafenib and Nivolumab in Mismatch Repair (MMR) Proficient Advanced Refractory Colorectal Cancer

To determine the maximum tolerated dose of Regorafenib in combination with Nivolumab in advanced, refractory colorectal cancers.

To access response rate using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

To evaluate the frequency and severity of adverse events and tolerability of the combination regimen.

Bristol-Myers Squibb

H. Lee Moffitt Cancer Center and Research Institute

Infections

Mouth and Tooth Diseases

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Measles

Rubella

Mumps

Warts

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

Micronutrients

Hypoglycemic Agents

Bone Density Conservation Agents

Vitamins

Lidocaine

Vaccines

Insulin

Insulin, Globin Zinc

Immunomodulating Agents

Vitamin D

Cholecalciferol

Trace Elements

Vitamin D3

Calciferol

All Group A patients will receive intralesional MMR.

All Group B patients will receive intralesional Vitamin D3

Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.

Measles-Mumps-Rubella Vaccine

Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier

Vit D

Bibisha Baaniya, MBBS

Common warts are papulonodular epidermal lesions caused by human papillomavirus (HPV) usually by the strains 1, 2, 4, 27 or 57. Cutaneous warts occur in 7% to 10% of the general population, with a maximum incidence between 12 and 16 years. There are multiple destructive treatment modalities of wart but they have many adverse effects. Hence immunotherapy is becoming popular in treatment of warts. It is believed that the injection to the HPV-infected tissue induces a strong nonspecific pro-inflammatory signal and attracts the antigen-presenting cells. Which then promotes a Th1 cytokine response and leads to delayed-type hypersensitivity reaction leading to the eradication of the HPV-infected cells.

We are undertaking a study to evaluate and compare the safety and efficacy of 2 such immunotherapeutic agents namely, IL measles, mumps and rubella (MMR) vaccine versus IL vitamin D3 for the treatment of warts.

RESEARCH HYPOTHESIS Null Hypotheses: IL MMR vaccine is not better than IL Vitamin D in the treatment of wart Alternative hypothesis: IL MMR vaccine is better than IL Vitamin D in the treatment of wart

Method: A total of 60 patients will be included in the study, 30 in each group. Group A and Group B patients will be injected with 0.5 ml of IL MMR and 0.5 ml of IL vitamin D3 respectively into a single or a maximum of 5 warts at a time in case of multiple warts. The IL injection will be given every 3 weeks for a maximum of 5 doses. Clinical assessment will be done by taking photographs and measurements at baseline, before each treatment session, and 3 months after the completion of treatment. The response will be evaluated by a decrease in the size and number of the wart(s) and photographic comparison. The response will be considered complete if there is a complete clearance of the wart(s), good if the wart(s) will regress in size by 75-99%, moderate if they regress by 50-74% and no or mild if there will be a 0-49% decrease in wart(s). Immediate and late side effects of MMR and Vitamin D will be evaluated after each session. Follow up will be made monthly for 3 months to detect any recurrence. Quality of life (QoL) will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up.

Statistical analysis will be done using Statistical Package for the Social Sciences 10.5 version.

INTRODUCTION Warts are common skin conditions resulting from infection of keratinocytes by human papillomavirus (HPV). After infection of the basal layer, there is clonal proliferation leading to epidermal thickening and hyperkeratinization and eventually results in a visible wart. HPVs are ubiquitous, epitheliotropic non-enveloped small double-stranded DNA viruses. Over 150 types of HPVs have been identified. Among them verruca vulgaris are usually caused by HPV types 1, 2, 4, 27 or 57, and plane warts by HPV types 3 or 10.

Cutaneous warts occur in 7% to 10% of the general population, with a maximum incidence between the ages of 12 and 16 years. In children, clearance can occur after only a few months, with 50% at 1 year and about 65%-78% by 2 years. The rate of clearance is influenced by factors like virus strain, host immune status, extent and duration of warts. The transmission of warts occurs from direct contact or indirectly via fomites.

There are multiple destructive, antiproliferative and antiviral agents in treatment of warts. Other modalities include hypnotherapy, acupuncture, local hyperthermia, therapeutic vaccination and combinations of the previous agents. Destructive therapies usually come with many adverse effects hence immunotherapy is becoming more popular, especially in the treatment of refractory cutaneous and genital warts. These include various topical, intralesional (IL) and systemic agents. IL Measles, Mumps, rubella (MMR) and IL vitamin D3 are examples of immunotherapeutic agents.

Immunotherapy is defined as a type of biological therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases. Immunotherapy can affect the immune system in general or can be cell-specific.

Immunotherapy is believed to induce a strong nonspecific pro-inflammatory signal and attract the antigen-presenting cells. This is associated with the release of cytokines such as IL-2, IL-8, IL-12, IL-I8, tumor necrosis factor-α, and interferon-γ. This then promotes a Th1 cytokine response which leads to the activation of delayed-type hypersensitivity reaction leading to the eradication of the HPV-infected cells. Furthermore, the trauma of the injection may also cause a resolution in previously sensitized individuals. Vitamin D3 is also claimed to regulate epidermal cell differentiation and proliferation and may modulate cytokine production through its action upon vitamin D receptors (VDRs). Since IL antigen immunotherapy enhances recognition of the virus by the immune system it causes clearance of both treated and untreated lesions and helps to prevent future clinical infection through induction of long-term acquired immunity to HPV.

MMR vaccine is included in immunization schedule of Nepal so pre-sensitization skin test is not needed as all patients are expected to be immune. The presence of 3 different antigens in MMR increases the sensitivity to the injected antigen and decreases the likelihood of anergy. Side effects of MMR include pain during injection, flu-like symptoms, pruritus and burning sensation.

IL vitamin D is a novel addition to therapies in warts as it is a simple, effective, well-tolerable, and inexpensive method with negligible local and systemic side effects. Side effects of Vitamin D3 include transient mild to moderate pain, edema at the site of injection and mild erythema. Additionally, it would be safer to monitor serum vitamin D and calcium levels before and after intralesional vitamin D treatment to prevent possible hypervitaminosis D.

RATIONALE Intralesional Immunotherapy is an emerging method of treatment of wart in which injection in a single wart causes the resolution of distant warts as well. Compared to other destructive modalities, it is more effective and comfortable for the patient as it obviates the need for individual treatment of each wart. In addition it has a lower rate of recurrence, avoids adverse effects such as scarring, is more cost-effective in multiple warts and decreases the time a physician has to spend on each patient. Further both injection MMR and Vitamin D3 are readily available as compared to other immunotherapeutic agents like purified protein derivative and candida antigen.

IL MMR vaccine has been used for a longer time than IL vitamin D and there are more comparative studies showing efficacy of MMR vaccine with rates of clearance ranging from 70.4% to 82.4%. The clearance rates for IL vitamin D ranges from 40% to 90%.

The advantages of vitamin D over MMR vaccine are cost-effectiveness, non-requirement of maintenance of cold chain, easy availability, and feasibility of use in immunosuppressed patients.

As per Institute of Medicine (IOM), the tolerable upper intake of vitamin D is 4000 IU/day for anyone older than 9 years such that annual maximum dose will be 1,460,000 IU. The total amount of vitamin D that we will be administering will be 1,500,000 IU. Furthermore, since we are giving it intralesionally systemic absorption is likely to be low although data on exact amount of IL vitamin D that gets absorbed systemically is not available. In other studies, patients have been evaluated clinically for signs and symptoms of hypervitaminosis D however, no signs of toxicity were observed.

As per our literature search,

1. No previous studies on immunotherapy in wart have been conducted in our country
2. No comparative studies have been done to compare IL MMR and IL vitamin D3 in treatment of wart hence we aim to establish efficacy of each and compare the two.

OBJECTIVES

Primary Objectives:

1. To determine the efficacy of IL MMR vaccine in the treatment of Wart
2. To determine the efficacy of IL vitamin D in the treatment of wart
3. To compare the efficacy of IL MMR vaccine and IL Vitamin D

Secondary Objective:

1. To determine the clinical and demographic profile of patients with different types of warts visiting Dermatology outpatient department(OPD) of BP Koirala Institute of Health Sciences (BPKIHS)
2. To determine the side effects of IL MMR vaccine and IL Vitamin D in treatment of wart
3. To determine Dermatology life quality index (DLQI) in wart patients.

Operational definition Wart - clinical diagnosis made by a dermatologist Complete response (100%)- Complete disappearance of warts including distant ones and skin texture at the site is restored to normal Excellent response (75-99%)-Reduction in size and number including distant ones and few residual warts still visible Good response (50-74%)-Some reduction in size only including that of distant ones but no decrease in number of warts Poor or no response (0-49%)-No significant change in size and number of warts Recurrence- Recurrence during the study period

MATERIALS AND METHODOLOGY Materials: Study population will be all patients clinically diagnosed with warts visiting the Dermatology OPD of BPKIHS, Dharan.

Study design: Prospective comparative longitudinal study Study Period: Probable duration of the study will be 1 year after approval from the Institutional Review Committee (IRC) and Nepal Health Research Council (NHRC) Ethical Clearance: Taken from IRC, BPKIHS and NHRC Conflict of interest: None Sampling Technique: Census method with all consecutive patients meeting inclusion criteria for initial 6 months Sample size The study considers a 95% confidence interval, 80% power to estimate sample size. According to the literature review, it was found that there was 84.6% and 40% improvement in MMR and Vitamin D respectively.

Now using the sample size estimation formula for 2 proportion {(Zα√2p(1-p)+ Z1-β√((p1(1-p1) p2(1-p2)}2))/(p1-p2)2 Where n= sample size for each group p1 = 0.846 p2 = 0.40 p= (p1 +p2)/2 Zα=1.96 Z1-β = 1.28 Using above formula, n= 12.3 The formula for actual sample size is n/4{1+√(1+4/n\|p1-p2\|)}2 na = 16.48 Adding 10% in calculated value to reduce bias sampling technique, the minimum sample size in each group is 18.13 =19 Considering loss of follow up, sample size in each group= 30 Total sample size= 60

Methodology Based on the computer generated random number table, patients satisfying inclusion criteria will be assigned to either Group A or Group B once they come to OPD. Informed consent will be taken and detailed information including personal data, past history, medical history, drug history, clinical data like site, size, number and distribution of lesions will be recorded in preset pro forma. Photographs of the lesions will be taken before the first treatment session, in every treatment session and 3 months after last session.

Group A Freeze-dried MMR vaccine single-use vials stored at 2°C-8°C will be reconstituted with 0.5 mL of distilled water immediately before IL use. If reconstituted vaccine is not used within 8 hours it must be discarded. All Group A patients will receive IL injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts with 31 G insulin syringe with beveled edge facing upward. Amount of injection on each wart will depend on the size of each wart. The injection will be given every three weeks for a maximum of 5 doses.

Group B All Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. Amount of injection on each wart will depend on the size of each wart. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier. In patients of group B serum vitamin D level will be measured after 20 days of 3rd dose and 1 month after the last dose to ensure safe monitoring.

Patient and physician global assessment using 'Visual Analog Scale score' and photographic comparison will be used to assess the response to treatment as mentioned in operational definition. Immediate and late adverse effects in both groups will be evaluated after each treatment session. Necessary investigations and intervention will be done if needed. Follow up will be made monthly for 3 months to detect any recurrence.

Quality of Life(QoL) QoL will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Questions 1 and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and school; 8 and 9, personal relationships and 10, treatment. The clinically meaningful change or reduction in the DLQI score is measured as the change in score from one band to the other.

Statistical analysis

1. Data handling: Data will be entered in Microsoft Excel 2010 and statistical analysis will be done using Statistical Package for the Social Sciences 10.5 version
2. Coding: Alpha numerical code will be used
3. Monitoring: Data will be entered after every day of work and supervised by guide.
4. Statistical Analysis:

   1. Chi square test to compare the categorical data between the groups.
   2. Paired t test for comparing normally distributed continuous variables at different time point within the group
   3. Independent 't' test for comparing normally distributed continuous variables at different time point between the groups
   4. Wilcoxon signed rank test to compare the not normally distributed variables, ordinal data
   5. Mann- Whitney U test to compare the not normally distributed variables, ordinal data.
   6. Kaplan-Meier curves to compare the response rate on each follow up visit between the groups.

Test of significance will be considered when value of p ≤ 0.05.

Group A - will receive IL MMR Group B- will receive IL Vitamin D3

Only patients will be blinded to the randomization and intervention.

A Comparative Study to Assess Efficacy of Intralesional MMR Vaccine and Intralesional Vitamin D3 in Treatment of Warts

A Comparative Study to Assess Efficacy of Intralesional MMR (Measles, Mumps, Rubella) Vaccine and Intralesional Vitamin D3 in Treatment of Warts

Number of participants with different progressions of warts like Gradual or rapid or stable or regressing lesions

Frequency of different types of past treatment taken- either traditional or medical treatments

Percentage of patients showing complete response to IL MMR and IL Vitamin D3

Complete response -Complete disappearance of warts including distant ones and skin texture at the site is restored to normal (100%) Excellent response- Reduction in size and number including distant ones and few residual warts still visible (75-99%) Good response- Some reduction in size only including that of distant ones but no decrease in number of warts (50-74%) Poor or no response- No significant change in size and number of warts (0-49%)

Distribution of wart patients into different education level like professional degree, graduate, intermediate, high school, middle school, primary school or illiterate

Number of participants with different occupations like professional, semiprofessional, clerical/shop/farm, skilled worker, semiskilled worker, unskilled worker, unemployed

Quality of life (QoL) will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Questions 1 and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and school; 8 and 9, personal relationships and 10, treatment.

The DLQI consists of 10 questions. Each question is given 4 options from not at all effect (score 0) to very much effect (score 3). The minimum and maximum possible score, thus, is 0 and 30 respectively.

Meaning of DLQI Scores 0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life

.

Nepal Health Research Council

B.P. Koirala Institute of Health Sciences

Junior Resident

All Group A patients will receive intralesional MMR.

Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.

Measles, Mumps, Rubella Vaccine

All Group B patients will receive intralesional Vitamin D3

Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)	NCT01570868	Leukemia	Ponatinib	18 Years -	M.D. Anderson Cancer Center
Calibration of MR and PET-MR Imaging Protocols at RIC	NCT02249520	Cancer Coronary Artery...	PET-MR imaging ... MR-only imaging... MR imaging on t...	18 Years -	Cedars-Sinai Medical Center
Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors	NCT04795427	Leukemia, Chron...	asciminib best available ...	18 Years -	Novartis
Regorafenib and Nivolumab in Mismatch Repair (MMR) Refractory Colorectal Cancer	NCT03712943	Colorectal Canc... Metastatic Colo... Colon Cancer	Regorafenib Nivolumab	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)	NCT01570868	Leukemia	Ponatinib	18 Years -	M.D. Anderson Cancer Center
A Comparative Study to Assess Efficacy of Intralesional MMR Vaccine and Intralesional Vitamin D3 in Treatment of Warts	NCT04428359	Verruca Viral	Measles-Mumps-R... Vit D	12 Years -	B.P. Koirala Institute of Health Sciences
Prognostic Biomarkers in Patients With Urothelial Carcinoma	NCT04872036	Bladder Cancer		18 Years -	Hellenic Cooperative Oncology Group
Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation	NCT04666259	Chronic Myeloge...	ABL001	18 Years -	Novartis
Regorafenib and Nivolumab in Mismatch Repair (MMR) Refractory Colorectal Cancer	NCT03712943	Colorectal Canc... Metastatic Colo... Colon Cancer	Regorafenib Nivolumab	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)	NCT01570868	Leukemia	Ponatinib	18 Years -	M.D. Anderson Cancer Center
Prognostic Biomarkers in Patients With Urothelial Carcinoma	NCT04872036	Bladder Cancer		18 Years -	Hellenic Cooperative Oncology Group
Endometrial Cancer Patientes MMR Deficient Comparing Chemotherapy vs Dostarlimab in First Line	NCT05201547	Endometrial Can...	Carboplatin-Pac... Dostarlimab	18 Years -	ARCAGY/ GINECO GROUP

Spots Global Cancer Trial Database for mmr

Every month we try and update this database with for mmr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for mmr

Every month we try and update this database with for mmr cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mmr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.