protocol_id stringclasses 263
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NCT01296932 | 5.4 | APPROPRIATENESS OF MEASUREMENTS | 5.4 APPROPRIATENESS OF MEASUREMENTS Determination of MTD is based on toxicities graded according to CTCAE ([R10-4848\)](#page-69-0). The CTCAE criteria are commonly used in the assessment of adverse events in cancer patients. The criteria to be used for evaluation of response [\(R10-4429](#page-68-0)) are well establis... | [] |
NCT01296932 | 6 | INVESTIGATIONAL PLAN | 6. INVESTIGATIONAL PLAN | [] |
NCT01296932 | 6.1 | VISIT SCHEDULE | 6.1 VISIT SCHEDULE During the treatment phase, after administration of BI 836826, patients are required to be hospitalized under close surveillance with access to intensive care for at least 48 hours after the second dose of BI 836826 in course 1 to allow close monitoring for infusion-related reactions, tumour lysis sy... | [] |
NCT01296932 | 6.2 | DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS | 6.2 DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS The investigations as outlined in the [Flow Chart](#page-5-0) will be performed at the respective visits as described in detail in the following sections. | [] |
NCT01296932 | 6.2.1 | Screening period | 6.2.1 Screening period The screening period, i.e. the phase after informed consent and before the first administration of the trial drug, may be as long as 14 days. The following parameters and investigations will be obtained and / or performed: - Informed consent - Demographics (sex, birth date, race) - Medical histor... | [] |
NCT01296932 | 6.2.2 | Treatment periods | 6.2.2 Treatment periods | [] |
NCT01296932 | 6.2.2.1 | Visit 1 - day 1 (day 1 of a treatment course) | 6.2.2.1 Visit 1 - day 1 (day 1 of a treatment course) On the treatment days, the following parameters and investigations will be obtained and / or performed: - Review of inclusion and exclusion criteria (patient eligibility), in the first cycle only - Blood samples for pharmacogenetic investigations (optional, only aft... | [] |
NCT01296932 | 6.2.2.2 | Visit 1 - day 2 (day 2 of a treatment course) | 6.2.2.2 Visit 1 - day 2 (day 2 of a treatment course) On the day after the treatment, the following parameters and investigations will be obtained/performed - Administration of BI 836826 only in course 1 - Vital signs at time points specified in [Section](#page-46-0) 5.2.5.1 - Adverse events - Concomitant therapy - Saf... | [] |
NCT01296932 | 6.2.2.3 | Visit 2 - day 3 (day 3 in course 1 or day 3 (+2) in course 2-8) | 6.2.2.3 Visit 2 - day 3 (day 3 in course 1 or day 3 (+2) in course 2-8) On visit 2, the following parameters and investigations will be obtained/performed - Vital signs (see [Section](#page-46-0) 5.2.5.1) - Adverse events - Concomitant therapy - Safety lab parameters as specified in Section 5.2.3.1 6.2.2.4 Visit 2 - da... | [] |
NCT01296932 | 6.2.3 | End of trial and follow-up period | 6.2.3 End of trial and follow-up period | [] |
NCT01296932 | 6.2.3.1 | End of treatment | 6.2.3.1 End of treatment The end of treatment (EOT) visit should be performed 14 days (± 2 days) after the last administration of BI 836826. If the patient concludes the trial within a treatment cycle not at the end of a treatment cycle, the information required to be collected at the EOT visit should be obtained immed... | [] |
NCT01296932 | 6.2.3.2 | Follow-up | 6.2.3.2 Follow-up Follow-up visits will be performed after the EOT visit in case a patient has completed treatment according to protocol or is not eligible for further treatment courses prior to administration of the maximum number of courses. Follow up will end in case the patient is lost to follow-up, receives new an... | [] |
NCT01296932 | 6.2.3.3 | End of the whole trial | 6.2.3.3 End of the whole trial The clinical trial will be analyzed and reported after the last patient has completed his / her last visit. In case the trial is ended by the sponsor when patients are still being treated with BI 836826 when the final report of the trial is being prepared, the patients will either be incl... | [] |
NCT01296932 | 7 | STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE | 7. STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE | [] |
NCT01296932 | 7.1 | STATISTICAL DESIGN - MODEL | 7.1 STATISTICAL DESIGN - MODEL This trial will be performed as an open-label study. The primary objective of the trial is to determine the MTD of BI 836826. To determine the MTD, patients are entered sequentially into escalating dose tiers, initially in single patient cohorts and later on using the 3+3 design (see [Sec... | [] |
NCT01296932 | 7.2 | NULL AND ALTERNATIVE HYPOTHESES | 7.2 NULL AND ALTERNATIVE HYPOTHESES The analyses in this trial are descriptive and exploratory. No formal statistical tests will be performed. | [] |
NCT01296932 | 7.3 | PLANNED ANALYSES | 7.3 PLANNED ANALYSES | [] |
NCT01296932 | 7.3.1 | Primary analyses | 7.3.1 Primary analyses The primary objective for this study is the tolerability and safety of BI 836826 as reflected by the MTD (for a definition of MTD, please refer to [Section 3.1](#page-21-0)). In order to identify the MTD, the number of DLTs at each dose level must be presented. For the analysis of tolerability an... | [] |
NCT01296932 | 7.3.2 | Secondary analyses | 7.3.2 Secondary analyses | [] |
NCT01296932 | 7.3.2.1 | Number of lymphocytes in the peripheral blood | 7.3.2.1 Number of lymphocytes in the peripheral blood The number and the change of lymphocytes in the peripheral blood will be analysed descriptively by time point. The maximal reduction of lymphocytes with respect to all time points after baseline will be analysed.  | [] |
NCT01296932 | 7.3.2.4 | Blood counts | 7.3.2.4 Blood counts Blood counts will be analysed as part of the laboratory tests (see [Section](#page-60-0) 7.3.3) | [] |
NCT01296932 | 7.3.2.5 | Best overall response | 7.3.2.5 Best overall response Best overall response is the best response (CR, PR, SD or PD in this order) with respect to all time points. Remission rate is the rate of patients that either have CR or PR as best overall response. Best overall response and remission rate will be analysed descriptively. Frequency distrib... | [] |
NCT01296932 | 7.3.3 | Safety analyses | 7.3.3 Safety analyses The occurrence of dose limiting toxicity (DLT) as well as the incidence and intensity of adverse events graded according to CTCAE, laboratory parameters and vital signs will be evaluated. Incidence and intensity of adverse events The severity, and timing of adverse events will indicate how well th... | [] |
NCT01296932 | 7.3.4 | Interim analyses | 7.3.4 Interim analyses The sponsor and the DSMB will perform interim safety evaluations as considered necessary. No formal interim analyses of efficacy data are foreseen, although efficacy data may be considered as part of the interim safety evaluations considered above. If considered necessary, as soon as the MTD is d... | [] |
NCT01296932 | 7.4 | HANDLING OF MISSING DATA | 7.4 HANDLING OF MISSING DATA No imputation will be performed on missing efficacy data. Missing baseline laboratory values will be imputed by the respective values from the screening visit. No other imputations will be performed on missing data although every effort will be made to obtain complete information on all adv... | [] |
NCT01296932 | 7.5 | RANDOMISATION | 7.5 RANDOMISATION No randomisation will be performed. Patients will be assigned into escalating dose groups by order of admission into the trial. Boehringer Ingelheim 04 Mar 2015 BI Trial No.: 1270.1 c01568809-08 Trial Protocol Page 64 of 111 | [] |
NCT01296932 | 7.6 | DETERMINATION OF SAMPLE SIZE | 7.6 DETERMINATION OF SAMPLE SIZE Assuming 3 cohorts of 1 patient only, 3 cohorts of 3 patients (i.e. no patients with DLT at given level) and 3 cohorts of 6 patients (i.e. 1 DLT witnessed in first 3 patients so further 3 patients exposed with no DLTs), 30 patients will be necessary for the dose escalation part of this ... | [] |
NCT01296932 | 8 | INFORMED CONSENT, DATA PROTECTION, TRIAL RECORDS | 8. INFORMED CONSENT, DATA PROTECTION, TRIAL RECORDS The trial will be carried out in compliance with the protocol, the principles laid down in the Declaration of Helsinki, version as of October 1996 (as long as local laws do not require to follow other versions), in accordance with the ICH Harmonised Tripartite Guideli... | [] |
NCT01296932 | 8.1 | STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED CONSENT | 8.1 STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED CONSENT This trial will be initiated only after all required legal documentation has been reviewed and approved by the respective Institutional Review Board (IRB) / Independent Ethics Committee (IEC) and competent authority (CA) according to national and internation... | [] |
NCT01296932 | 8.2 | DATA QUALITY ASSURANCE | 8.2 DATA QUALITY ASSURANCE The trial will be conducted in compliance with the protocol, the principles laid down in the Declaration of Helsinki version 1996 (please, refer to [Section 8](#page-64-0)), local law and according to the principles of GCP and the company standard operating procedures (SOPs). To inform all in... | [] |
NCT01296932 | 8.3 | RECORDS | 8.3 RECORDS Case Report Forms (CRFs) for individual patients will be provided by the sponsor, either on paper or via remote data capture. For drug accountability, refer to [Section 4.1.8.](#page-31-0) | [] |
NCT01296932 | 8.3.1 | Source documents | 8.3.1 Source documents Source documents provide evidence for the existence of the patient and substantiate the integrity of the data collected. Source documents are filed at the investigator's site. Data entered in the eCRFs that are transcribed from source documents must be consistent with the source documents or the ... | [] |
NCT01296932 | 8.3.2 | Direct access to source data and documents | 8.3.2 Direct access to source data and documents The investigator / institution will permit trial-related monitoring, audits, IRB / IEC review and regulatory inspection, providing direct access to all related source data / documents. CRFs/eCRFs and all source documents, including progress notes and copies of laboratory... | [] |
NCT01296932 | 8.4 | LISTEDNESS AND EXPEDITED REPORTING OF ADVERSE EVENTS | 8.4 LISTEDNESS AND EXPEDITED REPORTING OF ADVERSE EVENTS | [] |
NCT01296932 | 8.4.1 | Listedness | 8.4.1 Listedness To fulfil the regulatory requirements for expedited safety reporting, the sponsor evaluates whether a particular adverse event is "listed", i.e. is a known side effect of the drug or not. Therefore a unique reference document for the evaluation of listedness needs to be provided. For BI 836826 this is ... | [] |
NCT01296932 | 8.4.2 | Expedited reporting to health authorities and IECs/IRBs | 8.4.2 Expedited reporting to health authorities and IECs/IRBs Expedited reporting of serious adverse events, e.g. suspected unexpected serious adverse reactions (SUSARs) to health authorities and IECs/IRBs, will be done according to local regulatory requirements. Further details regarding this reporting procedure are p... | [] |
NCT01296932 | 8.5 | STATEMENT OF CONFIDENTIALITY | 8.5 STATEMENT OF CONFIDENTIALITY Individual patient medical information obtained as a result of this trial is considered confidential and disclosure to third parties is prohibited with the exceptions noted below. Patient confidentiality will be ensured by using patient identification code numbers. Treatment data may be... | [] |
NCT01296932 | 8.6 | COMPLETION OF TRIAL | 8.6 COMPLETION OF TRIAL The EC/competent authority in each participating EU member state needs to be notified about the end of the trial (last patient/patient out, unless specified differently in [Section 6.2.3](#page-56-0) of the CTP) or early termination of the trial. | [] |
NCT01296932 | 9 | REFERENCES | 9. REFERENCES | [] |
NCT01296932 | 9.1 | PUBLISHED REFERENCES | 9.1 PUBLISHED REFERENCES | R01-0028 | Simon R, Freidlin B, Rubinstein L, Arbuck SG, Collins J, Christian MC.Acceleratedtitration designs for phase I clinical trials in oncology. J NatlCancer Inst 1997;89(15):1138-1147 | |----------|----------------------------------------------------------------------------------------... | [] |
NCT01296932 | 9.2 | UNPUBLISHED REFERENCES | 9.2 UNPUBLISHED REFERENCES U10-1892-01 Investigator's Brochure: BI 836826 (Version 1). 15 June 2010. | [] |
NCT01296932 | 10 | APPENDICES | 10. APPENDICES      BI Trial No.: 1270.1 c01568809-08 Trial Protocol Page 74 of 111 | [] |
NCT01296932 | 10.4 | EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE SCORE | 10.4 EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE SCORE | Grade | Description | |-------|-------------------------------------------------------------------------------------------------------------------------------------------------------------| | 0 | Fully active, able to carry on all pre-disease performanc... | [] |
NCT01296932 | 10.5 | CLINICAL EVALUATION OF LIVER INJURY | 10.5 CLINICAL EVALUATION OF LIVER INJURY | [] |
NCT01296932 | 10.5.1 | Introduction | 10.5.1 Introduction Alterations of liver laboratory parameters, as described in [Section 5.2.2.1](#page-39-0) (Protocol-Specified Significant Adverse Events), are to be further evaluated using the following procedures: | [] |
NCT01296932 | 10.5.2 | Procedures | 10.5.2 Procedures Repeat the following lab tests: ALT, AST, and bilirubin (total and direct) - within 48 to 72hours. If ALT and/or AST ≥3 fold ULN combined with an elevation of total bilirubin ≥2 fold ULN are confirmed (if normal values at baseline/screening), or ALT and/or AST >5 fold ULN combined with an elevation of... | [] |
NCT01296932 | 10.6 | FLOW CHART FOR COURSE 1, IN CASE THE TOTAL DOSE IN THIS COURSE IS DIVIDED INTO THREE PORTIONS ADMINISTERED ON DAY 1, DAY 2 AND DAY 8 | 10.6 FLOW CHART FOR COURSE 1, IN CASE THE TOTAL DOSE IN THIS COURSE IS DIVIDED INTO THREE PORTIONS ADMINISTERED ON DAY 1, DAY 2 AND DAY 8 Flow Chart for Course 1 with administration on Day 1, Day 2 and Day 8 | Trial Periods | Screen | | | Treatment | | | | EOTFU | |-----------------------------|-----------|---|---|----... | [] |
NCT01296932 | 11 | SUMMARY OF CLINICAL TRIAL PROTOCOL MODIFICATIONS | 11. SUMMARY OF CLINICAL TRIAL PROTOCOL MODIFICATIONS Summary of Clinical Trial Protocol Modifications Sheet (SOMS) | Number of CTP modification | 1 | |--------------------------------------------------|--------------------------------------------------------| | Date of CTP modification | 20 Jan 2011 | | EudraCT number ... | [
"Rationale for change Change 1: Change of responsibilities",
"APPROVAL / SIGNATURE PAGE",
"Signatures (obtained electronically)"
] |
NCT01504841 | A | PHASE I/II, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND ANTIVIRAL ACTIVITY OF ETRAVIRINE (ETR) IN ANTIRETROVIRAL (ARV) TREATMENT-EXPERIENCED HIV-1 INFECTED INFANTS AND CHILDREN, AGED ≥2 MONTHS TO <6 YEARS | A PHASE I/II, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND ANTIVIRAL ACTIVITY OF ETRAVIRINE (ETR) IN ANTIRETROVIRAL (ARV) TREATMENT-EXPERIENCED HIV-1 INFECTED INFANTS AND CHILDREN, AGED ≥2 MONTHS TO <6 YEARS A Multicenter, Domestic & International Trial of the International Maternal Pedia... | [] |
NCT01504841 | P1090 | PROTOCOL TEAM ROSTER | P1090 PROTOCOL TEAM ROSTER All questions concerning this protocol should be sent via e-mail to [impaact.teamp1090@fstrf.org.](mailto:impaact.teamp1090@fstrf.org) Questions concerning clinical management of study subjects and all communication regarding adverse experiences should be addressed to the P1090 core protocol ... | [
"Investigators",
"Janssen R&D Representatives",
"GLOSSARY",
"SCHEMA IMPAACT P1090",
"STUDY DURATION: Minimum of 48 weeks",
"PRIMARY OBJECTIVES:",
"SECONDARY OBJECTIVES:",
"1.0 INTRODUCTION",
"1.1 Background",
"1.2 Etravirine Background",
"1.21 General",
"1.22 Preclinical Studies",
"1.23 Phar... |
NCT01557400 | C | LI NI C A L P R O T O C O L | C LI NI C A L P R O T O C O L | [] |
NCT01557400 | N | O P E N L A B E L S T U D Y O R P R E VI O U S L Y T R E A T E D A T A L U R E N ( P T C 1 2 4®) P A TI E N T S WI T H N O N S E N S E M U T A TI O N D Y S T R O P HI N O P A T H Y | N O P E N L A B E L S T U D Y O R P R E VI O U S L Y T R E A T E D A T A L U R E N ( P T C 1 2 4®) P A TI E N T S WI T H N O N S E N S E M U T A TI O N D Y S T R O P HI N O P A T H Y Pr ot o c ol N u m b er P T C 1 2 4 G D 0 1 9 D M D 1 8 N o v e m b er 2 0 1 5 V er si o n . 0 P T C T h er a p e uti c s, I n c. 1 0 0 C... | [
"PROTOCOL IDENTIFIERS AND STUDY PERSONNEL",
"PTC THERAPEUTICS PROTOCOL APPROVAL SIGNATURES",
"PRINCIPAL INVESTIGATOR AGREEMENT AND SIGNATURE",
"ABBREVIATIONS",
"1. OVERVIEW",
"1.1. Background",
"1.2. Study Design",
"2. INTRODUCTION",
"2.1. Disease Indication",
"2.2. Ataluren (PTC124)",
"2.2.1. T... |
NCT01578707 | 1 | INTRODUCTION | 1. INTRODUCTION Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) are a malignancy of B-cells that predominantly affects the older population. Chemoimmunotherapy, in particular the combination of purine analogs (eg, fludarabine) with cyclophosphamide and rituximab, has become a standard for the treat... | [] |
NCT01578707 | 1.1 | Ibrutinib | 1.1. Ibrutinib "Ibrutinib" and "PCI-32765" refer to the same molecule; hereafter, "ibrutinib" will be used. Ibrutinib is 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo [3, 4 d] pyrimidin-1-yl]-1 piperidinyl]-2-propen-1-one and has a molecular weight of 440.50 g/mole (anhydrous basis). Ibrutinib is a white to off-wh... | [] |
NCT01578707 | 1.1.1 | Mechanism of Action of Ibrutinib | 1.1.1. Mechanism of Action of Ibrutinib Ibrutinib binds covalently to a cysteine residue (Cys-481) near the BTK active site and inhibits the enzymatic activity of purified BTK with a half maximal inhibitory concentration (IC50) of 0.5 nM ([Honigberg 2010;](#page-93-1) [Pan 2007](#page-94-0)). Covalent binding to Cys-48... | [] |
NCT01578707 | 1.1.2 | Cellular Selectivity of Ibrutinib | 1.1.2. Cellular Selectivity of Ibrutinib BTK expression is limited to cells of hematopoietic origin. The cellular selectivity of ibrutinib was demonstrated by the observation that ibrutinib inhibits antigen-receptor signaling in B-cells, but not in T-cells. In ex vivo stimulation assays, ibrutinib inhibits human BCR ac... | [] |
NCT01578707 | 1.2 | Summary of Nonclinical Data | 1.2. Summary of Nonclinical Data For more detailed and comprehensive information of ibrutinib, please refer to the Investigator's Brochure [\(IB\)](#page-93-2). | [] |
NCT01578707 | 1.2.1 | Nonclinical Pharmacology Studies | 1.2.1. Nonclinical Pharmacology Studies Ibrutinib was designed as a selective and covalent inhibitor of the BTK protein [\(Pan 2007](#page-94-0)). In vitro, ibrutinib is a potent inhibitor of BTK activity (IC50 = 0.39 nM). The irreversible binding of ibrutinib to Cys-481 in the active site of BTK results in sustained i... | [] |
NCT01578707 | 1.2.2 | Safety Pharmacology and Toxicology | 1.2.2. Safety Pharmacology and Toxicology No treatment-related effects were observed in the central nervous system or respiratory system in rats at any dose tested. Further, no treatment-related corrected QT interval (QTc) prolongation effect was observed at any tested dose in a cardiovascular study using telemetry-mon... | [] |
NCT01578707 | 1.3 | Summary of Clinical Data | 1.3. Summary of Clinical Data | [] |
NCT01578707 | 1.3.1 | Pharmacokinetics and Product Metabolism | 1.3.1. Pharmacokinetics and Product Metabolism Following oral administration of ibrutinib at doses ranging from 420 to 840 mg/day, exposure to ibrutinib increased proportionally with substantial intersubject variability. The mean terminal plasma elimination half life (t1/2) of ibrutinib ranged from 4 to 13 hours, with ... | [] |
NCT01578707 | 1.3.2 | Clinical Studies | 1.3.2. Clinical Studies As of 4 October 2011, over 300 patients with various B-cell malignancies have received ibrutinib in six clinical studies sponsored by Pharmacyclics. A total of 133 patients with CLL or SLL have received single-agent ibrutinib across two clinical studies: PCYC-04753 in patients with recurrent B-c... | [] |
NCT01578707 | 1.3.2.1 | Summary of Efficacy of Ibrutinib in CLL/SLL | 1.3.2.1. Summary of Efficacy of Ibrutinib in CLL/SLL In the Study PCYC-04753, 14/16 (87.5%) patients with CLL or SLL treated with ibrutinib met the protocol definition of evaluable for assessment of response. Twelve (12) of the 14 (86%) evaluable patients with CLL or SLL achieved a response by the International Worksho... | [] |
NCT01578707 | 1.3.2.2 | Summary of Clinical Safety of Ibrutinib | 1.3.2.2. Summary of Clinical Safety of Ibrutinib A brief summary of safety data from monotherapy studies is provided in below. For more comprehensive safety information please refer to the current version of the [IB.](#page-93-2) Additional safety information may be available for approved indications in regional prescr... | [] |
NCT01578707 | 1.3.3 | Risks | 1.3.3. Risks | [] |
NCT01578707 | 1.3.3.1 | Bleeding-related Events | 1.3.3.1. Bleeding-related Events There have been reports of hemorrhagic events in patients treated with ibrutinib, both with and without thrombocytopenia. These include minor hemorrhagic events such as contusion, epistaxis and petechiae; and major hemorrhagic events, some fatal, including gastrointestinal bleeding, int... | [] |
NCT01578707 | 1.3.3.2 | Leukostasis | 1.3.3.2. Leukostasis There were isolated cases of leukostasis reported in subjects treated with ibrutinib. A high number of circulating lymphocytes (> 400,000/µL) may confer increased risk. For subject and ibrutinib management guidance, refer to [Section 6.2.5.](#page-41-0) | [] |
NCT01578707 | 1.3.3.3 | Atrial Fibrillation | 1.3.3.3. Atrial Fibrillation Atrial fibrillation and atrial flutter have been reported in subjects treated with ibrutinib, particularly in subjects with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Subjects who develop arrhythmic symptoms (eg, palpitations, lighth... | [] |
NCT01578707 | 1.3.3.4 | Cytopenias | 1.3.3.4. Cytopenias Treatment-emergent Grade 3 or 4 cytopenias (neutropenia, thrombocytopenia, and anemia) were reported in subjects treated with ibrutinib. Subjects should be monitored for fever, weakness, or easy bruising and/or bleeding. | [] |
NCT01578707 | 1.3.3.5 | Interstitial Lung Disease (ILD) | 1.3.3.5. Interstitial Lung Disease (ILD) Cases of interstitial lung disease (ILD) have been reported in patients treated with ibrutinib. Monitor patients for pulmonary symptoms indicative of ILD. Should symptoms develop follow the protocol dose modification guidelines (see [Section](#page-41-1) 6.2.4). | [] |
NCT01578707 | 1.3.3.6 | Tumor Lysis Syndrome | 1.3.3.6. Tumor Lysis Syndrome There have been reports of tumor lysis syndrome (TLS) events in subjects treated with single-agent ibrutinib or in combination with chemotherapy. Subjects at risk of TLS are those with comorbidities and/or risk factors such as high tumor burden prior to treatment, increased uric acid (hype... | [] |
NCT01578707 | 1.3.3.7 | Lymphocytosis | 1.3.3.7. Lymphocytosis Upon initiation of treatment, a reversible increase in lymphocyte counts (ie, ≥ 50% increase from baseline and an absolute count > 5000/µL), often associated with reduction of lymphadenopathy, has been observed in most subjects with CLL/SLL treated with ibrutinib. This effect has also been observ... | [] |
NCT01578707 | 1.3.3.8 | Diarrhea | 1.3.3.8. Diarrhea Diarrhea is the most frequently reported non-hematologic AE with ibrutinib monotherapy and combination therapy. Other frequently reported gastrointestinal events include nausea, vomiting, and constipation. These events are rarely severe. Should symptoms be severe or prolonged, follow the protocol dose... | [] |
NCT01578707 | 1.3.3.9 | Infections | 1.3.3.9. Infections Infections (including sepsis, bacterial, viral, or fungal infections) were observed in subjects treated with ibrutinib therapy. Some of these reported infections have been associated with hospitalization and death. Although causality has not been established, cases of progressive multifocal leukoenc... | [] |
NCT01578707 | 1.3.3.10 | Rash | 1.3.3.10. Rash Rashes have been commonly reported in subjects treated with either single agent ibrutinib or in combination with other chemotherapy. In a randomized Phase 3 study (PCYC-1112-CA), rash occurred at a higher rate in the ibrutinib arm than in the control arm. Most rashes were mild to moderate in severity. Is... | [] |
NCT01578707 | 1.3.3.11 | Non-melanoma Skin Cancer | 1.3.3.11. Non-melanoma Skin Cancer Non-melanoma skin cancers have occurred in patients treated with ibrutinib. Monitor patients for the appearance of non-melanoma skin cancer. | [] |
NCT01578707 | 1.3.3.12 | Hypertension | 1.3.3.12. Hypertension Hypertension has been commonly reported in subjects treated with ibrutinib. Monitor subjects for new onset of hypertension or hypertension that is not adequately controlled after starting ibrutinib. Adjust existing anti-hypertensive medications and/or initiate anti-hypertensive treatment as appro... | [] |
NCT01578707 | 2 | STUDY RATIONALE | 2. STUDY RATIONALE This randomized, multicenter, open-label, Phase 3 study is designed to evaluate whether treatment with ibrutinib as a monotherapy results in a clinically significant improvement in PFS IND # 102,688 Version: Amendment 7 as compared to treatment with ofatumumab in patients with relapsed or refractory ... | [] |
NCT01578707 | 2.1 | Dose Selection Rationale for Ibrutinib | 2.1. Dose Selection Rationale for Ibrutinib A once daily 420 mg dose of ibrutinib has been selected for this Phase 3 study. This dose and regimen were selected in consideration of PK, pharmacodynamics, efficacy, and safety data obtained from Studies PCYC-04753 and PCYC-1102-CA as detailed in [Section](#page-22-0) 1.3. ... | [] |
NCT01578707 | 2.2 | Selection of Ofatumumab as Comparator | 2.2. Selection of Ofatumumab as Comparator Ofatumumab is a fully humanized type I anti-CD20 monoclonal antibody. In vitro, it mediates complement dependent cytotoxicity (CDC) against rituximab-resistant Raji cells and CLL cells with low expression of CD20. It appears to have greater potency in CDC than rituximab, as we... | [] |
NCT01578707 | 3 | STUDY OBJECTIVES | 3. STUDY OBJECTIVES | [] |
NCT01578707 | 3.1 | Primary Objective | 3.1. Primary Objective To evaluate the efficacy of ibrutinib compared to ofatumumab based on independent review committee (IRC) assessment of progression-free survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia Criteria (IWCLL, [Hallek 2008](#page-93-4)) with incorporation of the clarification for... | [] |
NCT01578707 | 3.2 | Secondary Objectives | 3.2. Secondary Objectives To compare between the two treatment groups in terms of:
Efficacy - To evaluate overall survival (OS) - To evaluate IRC-assessed overall response rate (ORR) per IWCLL 2008 criteria - To evaluate patient-reported outcome (PRO) by the Functional Assessment of Chronic Illness Therapy-Fatigue (FA... | [
"Efficacy",
"Safety"
] |
NCT01578707 | 3.3 | Exploratory Objectives | 3.3. Exploratory Objectives To evaluate and compare between the two treatment arms in terms of: - To evaluate Investigator-assessed PFS and ORR per IWCLL 2008 criteria - To evaluate improvement and/or resolution of disease-related symptoms - To evaluate PRO by European Organisation for Research and Treatment of Cancer ... | [] |
NCT01578707 | 4 | STUDY DESIGN | 4. STUDY DESIGN This is a randomized, multicenter, open-label, Phase 3 study designed to evaluate the safety and efficacy of ibrutinib as compared to ofatumumab in patients with relapsed or refractory CLL/SLL who have failed at least one prior line of therapy and are not considered appropriate candidates for treatment ... | [] |
NCT01578707 | 5 | SELECTION OF PATIENTS | 5. SELECTION OF PATIENTS | [] |
NCT01578707 | 5.1 | Inclusion Criteria | 5.1. Inclusion Criteria Patients will be considered for inclusion in this study if they meet all of the following criteria: - 1. Men and women ≥ 18 years of age - 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 - 3. Diagnosis of CLL/SLL that meets published diagnostic criteria [\(Hallek 2008\)](#... | [] |
NCT01578707 | 5.2 | Exclusion Criteria | 5.2. Exclusion Criteria Patients will be ineligible for this study if they meet any of the following criteria: - 1. Known central nervous system (CNS) lymphoma or leukemia - 2. Known prolymphocytic leukemia or history of or currently suspected Richter's transformation - 3. Missing or incomplete documentation of cytogen... | [] |
NCT01578707 | 6 | TREATMENTS | 6. TREATMENTS Patients will be randomized 1:1 to either Treatment Arm A or B.
Treatment Arm A: Ofatumumab IV Treatment is 12 IV doses over 24 weeks or until disease progression, unacceptable toxicity, or the patient meets any criteria specified in [Section](#page-76-1) 10, whichever occurs first. Administration of ofa... | [
"Treatment Arm A: Ofatumumab IV",
"Treatment Arm B: Ibrutinib PO"
] |
NCT01578707 | 6.1 | Ofatumumab | 6.1. Ofatumumab | [] |
NCT01578707 | 6.1.1 | Dosage and Administration | 6.1.1. Dosage and Administration | [] |
NCT01578707 | 6.1.1.1 | Premedication | 6.1.1.1. Premedication Patients should be premedicated 30 minutes to 2 hours prior to each dose of ofatumumab with 975-1000 mg acetaminophen/paracetamol; 10 mg Cetirizine orally or equivalent antihistamine, either IV or oral; and 100 mg IV prednisolone or equivalent corticosteroid. Corticosteroid dose reduction: - Do n... | [
"For Doses 3 through 8:",
"For Doses 10 through 12:"
] |
NCT01578707 | 6.1.1.2 | Dosage Regimen and Administration | 6.1.1.2. Dosage Regimen and Administration Ofatumumab should be diluted in 0.9% Sodium Chloride Injection, USP and administered as an IV infusion. Do not administer the drug as an IV push or bolus. The ofatumumab dosage and schedule is 12 doses administered as follows Week 1: 300 mg initial dose Weeks 2 through 8: 2,00... | [] |
NCT01578707 | 6.1.2 | Dose Delay | 6.1.2. Dose Delay Treatment with ofatumumab should be held for any unmanageable, potentially study drug-related toxicity that is Grade 3 or greater in severity. Additional information concerning dose delays can be found in Section 6.1.4. Any other clinically important events where dose delays may be considered appropri... | [] |
NCT01578707 | 6.1.3 | Dose Interruption | 6.1.3. Dose Interruption Interrupt infusion for infusion-related reactions of any severity. For Grade 4 infusion-related reactions, do not resume the infusion. For Grade 1, 2, or 3 infusion-related reactions, if reaction resolves or remains ≤ Grade 2, resume infusion including increasing infusion rate consistent with t... | [] |
NCT01578707 | 6.1.4 | Dose Discontinuation | 6.1.4. Dose Discontinuation The actions in [Table 1](#page-39-4) should be taken for the following toxicities: - Grade 4 ANC ( 7 days (Neutrophil growth factors are permitted per ASCO guidelines [\[Smith 2006\]](#page-94-2) and use must be recorded in the case report form [CRF]). - Grade 3 or 4 platelets (< 50,000/µL);... | [] |
NCT01578707 | 6.1.5 | Dose Reduction | 6.1.5. Dose Reduction As dose reductions are not outlined in the package insert, dose reductions are not allowed for ofatumumab during this study. | [] |
NCT01578707 | 6.1.6 | Precautions and Adverse Effects | 6.1.6. Precautions and Adverse Effects | [] |
NCT01578707 | 6.1.6.1 | Warnings and Precautions | 6.1.6.1. Warnings and Precautions Infusion-Related Reactions: Premedication and infusion parameters, as outlined in the package insert should be used. Monitor patients closely during infusions and interrupt infusion if any reaction occurs. Cytopenias: Monitor blood counts as outlined in the Schedule of Assessments [\(A... | [] |
NCT01578707 | 6.1.6.2 | Adverse Events | 6.1.6.2. Adverse Events The most common serious adverse events (SAEs) with ofatumumab were infections (including pneumonia and sepsis), neutropenia, and pyrexia. Infections were the most common AEs leading to drug discontinuation. Additional common AEs (≥10%) with ofatumumab were cough, diarrhea, anemia, fatigue, dyspn... | [] |
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