protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT03712358 | A | Phase I trial of PVSRIPO for Patients with Unresectable Melanoma | A Phase I trial of PVSRIPO for Patients with Unresectable Melanoma Sponsor: Istari Oncology, Inc. Funding Source: Istari Oncology, Inc. Protocol Source: Duke Cancer Institute Duke IRB#: Pro00090774 WIRB#: 20181772 IND# 14, 735
Principal Investigator Georgia Beasley, MD Department of Surgery 489 Seeley Mudd Building Du... | [
"Principal Investigator",
"Chief Medical Officer - Istari Oncology, Inc.",
"Sub-Investigator(s)",
"Statistician",
"Lead Study Coordinator",
"Regulatory Coordinator",
"Data Manager",
"CONFIDENTIAL",
"SUMMARY OF PROTOCOLAMENDMENT CHANGES",
"2. LIST OF TABLES AND FIGURES",
"List of Tables:",
"3. ... |
NCT03734016 | 1 | INTRODUCTION | 1. INTRODUCTION | [] |
NCT03734016 | 1.1 | Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | 1.1. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Chronic lymphocytic leukemia (CLL) is a malignant disorder of B lymphocytes. It is the most common leukemia in the Western world with an incidence of 4.2 in every 100,000 persons per year. The incidence increases to > 30 in 100,000 per year in people aged mor... | [] |
NCT03734016 | 1.2 | B-cell Receptor Signaling | 1.2. B-cell Receptor Signaling B-cell receptor signaling is an important component for the survival of CLL cells, with continuous or repetitive B-cell receptor signaling capable of enabling the growth of CLL cells [\(Petlickovski](#page-88-9) et al 2005; [Stevenson et al 2011\)](#page-88-10). The B-cell receptor signal... | [] |
NCT03734016 | 1.2.1 | Ibrutinib | 1.2.1. Ibrutinib Ibrutinib is a small-molecule inhibitor of BTK. Nonclinical studies have demonstrated inhibition of malignant B-cell proliferation and survival by ibrutinib in vivo, as well as cell migration and substrate adhesion in vitro. In patients with recurrent B-cell lymphoma, > 90% occupancy of the BTK active ... | [] |
NCT03734016 | 1.2.2 | Zanubrutinib | 1.2.2. Zanubrutinib Zanubrutinib (also known as BGB-3111) is a potent, specific, and irreversible BTK inhibitor with a favorable pharmacologic and pharmacokinetic (PK) profile. Zanubrutinib is different from ibrutinib in the following ways: - Zanubrutinib is more selective in the relative inhibition of BTK versus off-t... | [] |
NCT03734016 | 1.2.2.1 | Nonclinical Data for Zanubrutinib | 1.2.2.1. Nonclinical Data for Zanubrutinib Summaries of nonclinical studies are provided below. For more detailed information, please refer to the zanubrutinib Investigator's Brochure ([BGB-3111 Investigator's Brochure](#page-86-10)). Zanubrutinib is a potent, specific, and irreversible BTK kinase inhibitor with a 50% ... | [] |
NCT03734016 | 1.2.2.2 | Summary of Relevant Clinical Experience with Zanubrutinib | 1.2.2.2. Summary of Relevant Clinical Experience with Zanubrutinib
Dose Selection for Zanubrutinib In the first-in-human, Phase 1 study, BGB-3111-AU-003, the PK of zanubrutinib was linear between 40 and 320 mg orally once daily [\(BGB-3111 Investigator's Brochure\)](#page-86-10). The absorption of zanubrutinib is rapi... | [
"Dose Selection for Zanubrutinib",
"Preliminary Efficacy and Safety Data for Zanubrutinib in CLL/SLL Patients",
"Clinical Pharmacology"
] |
NCT03734016 | 1.2.2.3 | Benefit-Risk Assessment | 1.2.2.3. Benefit-Risk Assessment As of 16 September 2018, approximately 1200 patients have received zanubrutinib in completed and ongoing clinical trials evaluating zanubrutinib either as monotherapy or in combination with another agent. Available data for zanubrutinib in patients with CLL/SLL support a positive benefi... | [] |
NCT03734016 | 2 | STUDY OBJECTIVES | 2. STUDY OBJECTIVES
Primary: • To compare the efficacy of zanubrutinib versus ibrutinib as measured by overall response rate determined by investigator assessment
Secondary: - To compare the efficacy of zanubrutinib versus ibrutinib as measured by: - − Progression-free survival determined by investigator assessment a... | [
"Primary:",
"Secondary:",
"Exploratory:"
] |
NCT03734016 | 3 | STUDY DESIGN | 3. STUDY DESIGN | [] |
NCT03734016 | 3.1 | Summary of Study Design | 3.1. Summary of Study Design This is a Phase 3, randomized study of zanubrutinib versus ibrutinib in approximately 600 patients with R/R CLL/SLL. The primary efficacy endpoint is ORR determined by investigator assessment. While the primary efficacy endpoint is per investigator assessment, ORR per independent central re... | [
"Study Assessments:"
] |
NCT03734016 | 3.2 | Study Schema | 3.2. Study Schema Figure 1: Study Schema  Abbreviations: CLL, chronic lymphocytic leukemia; SLL, small lymphocytic lymphoma. Randomization will be stratified by age (< 65 years versus ≥ 65 years), geographic region (China versus non-China), refractory status (yes or no), and del17p/TP53 mutation ... | [] |
NCT03734016 | 3.3 | Blinding | 3.3. Blinding Treatment with zanubrutinib and treatment with ibrutinib will be open label; however, the assessment of ORR by independent central review (primary endpoint) will be blinded. | [] |
NCT03734016 | 3.4 | Study Rationale | 3.4. Study Rationale B-cell receptor signaling regulates multiple cellular processes, including proliferation, differentiation, apoptosis, and cell migration, and is essential for normal B-cell development and survival [\(Advani et al 2013\)](#page-86-11). It also plays an important role in survival of CLL cells. BTK h... | [] |
NCT03734016 | 3.5 | Duration of Study | 3.5. Duration of Study The total duration of this study is expected to be approximately 51 months based on assuming an expected enrollment duration of 24 months, and an estimated follow up of 27 months after the last patient is enrolled. | [] |
NCT03734016 | 3.5.1 | Study Drug Access at Study Closure | 3.5.1. Study Drug Access at Study Closure Patients, who in the opinion of the investigator, continue to benefit from study treatment with either zanubrutinib or ibrutinib may continue treatment with zanubrutinib after study closure by enrolling in the Zanubrutinib Long-Term Extension Study. This study is a rollover stu... | [] |
NCT03734016 | 4 | ELIGIBILITY CRITERIA | 4. ELIGIBILITY CRITERIA | [] |
NCT03734016 | 4.1 | Inclusion Criteria | 4.1. Inclusion Criteria Each patient eligible to participate in this study must meet ALL of the following criteria: - 1. Age 18 years or older - 2. Confirmed diagnosis of CLL or SLL that meets the IWCLL criteria ([Hallek et al 2008](#page-87-3)) - 3. CLL/SLL requiring treatment as defined by at least 1 of the following... | [] |
NCT03734016 | 4.2 | Exclusion Criteria | 4.2. Exclusion Criteria Each patient eligible to participate in this study must NOT meet any of the following exclusion criteria: - 1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation (biopsy based on clinical suspicion may be needed to rule out transformation) - 2. Clinical... | [] |
NCT03734016 | 5 | ENROLLMENT AND STUDY PROCEDURES | 5. ENROLLMENT AND STUDY PROCEDURES Study enrollment and procedures are summarized in the following subsections. The timing of all study procedures is provided in the Schedule of Assessments [\(Appendix](#page-104-0) 10). | [] |
NCT03734016 | 5.1 | Study Visit Schedule | 5.1. Study Visit Schedule Scheduled study visits are outlined in the Schedule of Assessments [\(Appendix](#page-104-0) 10). The study visit schedule is based around 28-day cycles, with visits expected to occur in D1 of a given cycle. The length of a cycle should remain 28-days regardless of any drug holds occurring dur... | [] |
NCT03734016 | 5.2 | Screening | 5.2. Screening Before screening procedures are conducted, the patient must sign an informed consent form (ICF). Study site personnel must explain to potential study participants all aspects of the study, including all scheduled visits and activities. A copy of the ICF will be given to the patient to read, and the patie... | [] |
NCT03734016 | 5.2.1 | Females of Childbearing Potential and Contraception | 5.2.1. Females of Childbearing Potential and Contraception A woman is considered of childbearing potential, ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Contracepti... | [] |
NCT03734016 | 5.2.2 | Patient Numbering | 5.2.2. Patient Numbering After obtaining informed consent, study site personnel will access the Interactive Response Technology (IRT) system to assign a unique patient number to a potential study participant. Patient number will be assigned in chronological order by site starting with the lowest number. Once a patient ... | [] |
NCT03734016 | 5.2.3 | Demographics | 5.2.3. Demographics Demographic factors such as age, gender, race, and ethnicity could influence the effects (safety and efficacy) of medicines and the risk/benefit assessment in different populations. Race and ethnicity data are collected in accordance with International Council for Harmonisation (ICH) guidance (ICH E... | [] |
NCT03734016 | 5.2.4 | Medical and Cancer History | 5.2.4. Medical and Cancer History Review all medical and cancer history after obtaining informed consent, including presence or absence of disease-related constitutional symptoms. Clinically significant medical history (ie, previous diagnoses, diseases, or surgeries) that does not pertain to the study indication, start... | [] |
NCT03734016 | 5.2.5 | Confirmation of Eligibility | 5.2.5. Confirmation of Eligibility The investigator will assess and confirm the eligibility of each patient. All screening procedure results and relevant medical history must be available before eligibility can be determined. All inclusion criteria must be met, and none of the exclusion criteria may apply. No eligibili... | [] |
NCT03734016 | 5.2.6 | Enrollment/Randomization | 5.2.6. Enrollment/Randomization Study treatment should commence within 5 days after randomization, although small extensions to this due to drug supply logistics are permissible with Sponsor approval. Interactive Response Technology (IRT) will be used to randomize patients to treatment arm and to assign study drug as a... | [] |
NCT03734016 | 5.3 | Study Drug Dispensation | 5.3. Study Drug Dispensation At visits where study drug dispensation occurs, study center personnel should ensure adequate drug supply for administration at home throughout the treatment phase as detailed in the pharmacy manual. Drug may be dispensed as frequently as once every 28-day cycle, but may be modified to less... | [] |
NCT03734016 | 5.4 | Pharmacokinetics | 5.4. Pharmacokinetics Blood will be collected to characterize the PK of zanubrutinib. Sparse PK samples will be collected from all patients assigned to Arm A (zanubrutinib) only at the timepoints as described in [Appendix](#page-104-0) 10. PK samples will only be collected from sites that are able to adequately follow ... | [] |
NCT03734016 | 5.5 | Safety Assessments | 5.5. Safety Assessments | [] |
NCT03734016 | 5.5.1 | Cardiac Function | 5.5.1. Cardiac Function An assessment of left ventricular ejection fraction will be performed and documented at Screening and as medically indicated. Note: An echocardiogram, multigated acquisition, and gated heart pool scan are all acceptable. | [] |
NCT03734016 | 5.5.2 | Physical Examination and Vital Signs | 5.5.2. Physical Examination and Vital Signs Physical examination, vital signs (sitting blood pressure, heart rate, and body temperature), weight, and review for arrhythmia signs/symptoms (eg, shortness of breath, dizziness, or fainting) will be performed at each study visit during study treatment and at the End of Trea... | [] |
NCT03734016 | 5.5.3 | ECOG Performance Status | 5.5.3. ECOG Performance Status ECOG performance status [\(Appendix](#page-98-0) 6) will be assessed at the Screening visit, each visit during study treatment, and at the End of Treatment Visit. | [] |
NCT03734016 | 5.5.4 | Electrocardiogram | 5.5.4. Electrocardiogram A 12-lead ECG will be performed locally in triplicate at screening for all subjects. During study treatment, ECGs will be performed as specified per the Schedule of Assessments [\(Appendix](#page-104-0) 10). Subjects should be in the semi-recumbent or supine position. | [] |
NCT03734016 | 5.5.5 | Concomitant Medications Review | 5.5.5. Concomitant Medications Review Record any new medications, changes in ongoing medications or procedures, and medications discontinued within the screening window (see Section [5.2\)](#page-32-0), and on study thereafter. | [] |
NCT03734016 | 5.5.6 | Adverse Events Review | 5.5.6. Adverse Events Review Record AEs that occurred during Screening on the medical history case report form and in the patient's source document. Collect non-serious AE information from the time of first dose of study drug through End of Treatment Visit. Information on all SAEs (regardless of relatedness) will be co... | [] |
NCT03734016 | 5.6 | Efficacy Assessments | 5.6. Efficacy Assessments Overall response to study treatment will be assessed at the timepoints outlined in [Appendix](#page-104-0) 10. Overall response will be determined as follows: - CLL: IWCLL criteria ([Hallek M](#page-87-0) et al 2008) with addition of treatment-related lymphocytosis ([Cheson et al 2012\)](#page... | [] |
NCT03734016 | 5.6.1 | Disease-Related Constitutional Symptoms | 5.6.1. Disease-Related Constitutional Symptoms Disease-related constitutional symptoms based on IWCLL criteria ([Hallek M](#page-87-0) et al 2008) (unexplained fever of ≥ 38oC; unexplained, recurrent drenching night sweats; or unexplained loss of > 10% body weight within the previous 6 months) will be evaluated as spec... | [] |
NCT03734016 | 5.6.2 | Physical Examination of Liver, Spleen, and Lymph Nodes | 5.6.2. Physical Examination of Liver, Spleen, and Lymph Nodes Record presence and extent of hepatomegaly, splenomegaly, and/or lymphadenopathy as specified per the Schedule of Assessments [\(Appendix](#page-104-0) 10). PD assessed by physical examination must be confirmed by a CT scan. | [] |
NCT03734016 | 5.6.3 | Computed Tomography | 5.6.3. Computed Tomography All patients must have baseline CT scan with contrast of neck, chest, abdomen, and pelvis and any other disease sites as specified in [Appendix](#page-104-0) 10. All efforts will be made to ensure that the imaging equipment, contrast agent, and person (investigator or radiologist) performing ... | [] |
NCT03734016 | 5.6.4 | Bone Marrow Examination | 5.6.4. Bone Marrow Examination The schedule of required bone marrow examinations is given in [Appendix](#page-104-0) 10. Details on these examinations and when they are required are given below:
Bone Marrow Biopsy - In lieu of performing a bone marrow procedure, a site can submit any of the following from a previously... | [
"Bone Marrow Biopsy",
"Bone Marrow Aspirate"
] |
NCT03734016 | 5.6.5 | Survival Status | 5.6.5. Survival Status Survival follow-up assessments may be conducted on an ad hoc basis for data analysis to monitor survival status for all patients in the study. The information may be confirmed via a phone call, medical records, or other methods. Refer to the Schedule of Assessments [\(Appendix](#page-104-0) 10). | [] |
NCT03734016 | 5.7 | Patient-Reported Outcomes | 5.7. Patient-Reported Outcomes Patients should complete the PROs per the Schedule of Assessments ([Appendix](#page-104-0) 10) before study drug is administered and prior to performing any other procedures. | [] |
NCT03734016 | 5.7.1 | EQ-5D-5L | 5.7.1. EQ-5D-5L The EQ-5D-5L is a standardized instrument for use as a measure of health outcome (The [EuroQol Group 1990;](#page-87-10) [Herdman et al 2011](#page-87-11)). Patients will self-rate their current state of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression by choosing 1 of 5 po... | [] |
NCT03734016 | 5.7.2 | EORTC QLQ-C30 | 5.7.2. EORTC QLQ-C30 The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. It is a copyrighted instrument, which has been translated and validated in over 100 languages and is used in more than 3000 studies worldwide. The EORTC QLQ-C30 includes 30 separate questions (items) re... | [] |
NCT03734016 | 5.7.3 | Self-administered Activity and Quality of Life Evaluation (Optional) | 5.7.3. Self-administered Activity and Quality of Life Evaluation (Optional) A self-administered, device-based quality of life questionnaire and activity tracker may be optionally consented to, per patient, in select countries. All evaluations will be self-administered via an application designed for select electronic m... | [
"Administration and Schedule"
] |
NCT03734016 | 5.8 | Laboratory Assessments | 5.8. Laboratory Assessments Laboratory assessments required during the trial are detailed below. Laboratory assessments will be performed at the timepoints specified in the Schedule of Assessments [\(Appendix](#page-104-0) 10) and may also be performed as medically necessary. On Cycle 1 Day 1 (day of first dose of stud... | [
"Study Central Laboratories versus Local Laboratories"
] |
NCT03734016 | 5.8.1 | Hematology | 5.8.1. Hematology CBC with differential includes hemoglobin, hematocrit, platelet count, red blood cell count, and white blood cell count with differential (neutrophil, lymphocyte, monocyte, eosinophil, and basophil). | [] |
NCT03734016 | 5.8.2 | Serum Chemistry | 5.8.2. Serum Chemistry Serum chemistry includes sodium, potassium, chloride, bicarbonate (carbon dioxide, or if neither is available carbon dioxide combining power), glucose, blood urea nitrogen (or serum urea), creatinine, calcium, phosphate (or phosphorus), magnesium, total bilirubin, total protein, albumin, ALT, AST... | [] |
NCT03734016 | 5.8.3 | Serum Immunoglobulins | 5.8.3. Serum Immunoglobulins Quantitative serum immunoglobulins (IgG, IgM, and IgA) will be measured. | [] |
NCT03734016 | 5.8.4 | Coagulation | 5.8.4. Coagulation The coagulation profile includes prothrombin time, which will also be reported as international normalized ratio, and activated partial thromboplastin time. The coagulation profile will be performed at Screening only and as clinically indicated. | [] |
NCT03734016 | 5.8.5 | Hepatitis B and C testing | 5.8.5. Hepatitis B and C testing Hepatitis B/C serologic markers and/or viral load will be tested at screening via study central laboratory. The hepatitis B testing includes HBsAg, HBcAb, and HBsAb, as well as HBV DNA by PCR if the patient is negative for HBsAg, but HBcAb positive (regardless of HBsAb status). The hepa... | [] |
NCT03734016 | 5.8.6 | Pregnancy Test | 5.8.6. Pregnancy Test A serum pregnancy test will be performed at Screening within 7 days of randomization and End of Treatment in women of childbearing potential. Any female patient who is pregnant will not be eligible for the study. Laboratory-based highly sensitive pregnancy tests (urine or serum) will be performed ... | [] |
NCT03734016 | 5.8.7 | HIV Testing | 5.8.7. HIV Testing Subjects with HIV infection are excluded from the study. HIV testing will be performed during Screening unless previous HIV test results from ≤ 4 weeks prior to Screening are available. | [] |
NCT03734016 | 5.9 | Biomarkers | 5.9. Biomarkers Samples for biomarkers will be collected as indicated in [Appendix](#page-104-0) 10. Details on these samples and when they are required are given below. | [] |
NCT03734016 | 5.9.1 | Del17p and Cytogenetics | 5.9.1. Del17p and Cytogenetics CLL/SLL is characterized by various mutations shown to be linked to favorable prognosis (del13q and hypermutation of IGHV) or poor prognosis (del17p, del11q, unmutated IGHV, mutations in TP53, ATM, and Notch1). Screening blood samples will be used for the assessment of prognostic biomarke... | [] |
NCT03734016 | 5.9.2 | Flow Cytometry for MRD | 5.9.2. Flow Cytometry for MRD Blood and bone marrow samples (see Section [5.6.4\)](#page-39-0) will be collected for the assessment of MRD by flow and molecular techniques as indicated in [Appendix](#page-104-0) 10. | [] |
NCT03734016 | 5.9.3 | TP53 Mutation and Other Molecular Analysis | 5.9.3. TP53 Mutation and Other Molecular Analysis Blood samples will also be collected for the assessment of the mutation status of relevant genes by molecular techniques including, but not limited to, TP53, IGHV, Notch, etc, as indicated in [Appendix](#page-104-0) 10. Samples taken at progression leading to permanent ... | [] |
NCT03734016 | 5.10 | Unscheduled Visits | 5.10. Unscheduled Visits Unscheduled visits may be performed at any time at the patient's or investigator's request and may include vital signs/focused physical examination; ECOG performance status; AE review; concomitant medications and procedures review; radiographic assessments; physical examination of liver, spleen... | [] |
NCT03734016 | 5.11 | Treatment Period | 5.11. Treatment Period The treatment period starts with the first day of assigned study treatment and ends 30 days following date of permanent study drug discontinuation (ie, 30 days after the final administered dose of zanubrutinib or ibrutinib) Patients may discontinue study drug treatment for any one of the reasons ... | [] |
NCT03734016 | 5.12 | Post-Treatment Period | 5.12. Post-Treatment Period | [] |
NCT03734016 | 5.12.1 | End of Treatment | 5.12.1. End of Treatment All patients who permanently discontinue study drug will have an End of Treatment Visit approximately 30 days after the last dose of study drug to collect AEs, including AEs that may have occurred or been ongoing after the patient discontinued study treatment. The investigator or his/her design... | [] |
NCT03734016 | 5.12.2 | Long-term Follow-up | 5.12.2. Long-term Follow-up All patients who discontinue study drug treatment and have yet to have documented and confirmed progression by independent central review will remain in the study and subsequently commence Long-term Follow-up, which includes monitoring survival status, subsequent therapies for CLL/SLL, and o... | [] |
NCT03734016 | 5.12.3 | Survival Follow-up | 5.12.3. Survival Follow-up Patients who have discontinued study treatment and have documented and confirmed progression by independent central review should enter Survival Follow-up, which consists of monitoring for survival status and subsequent therapies for CLL/SLL. There are no mandatory study visits during Surviva... | [] |
NCT03734016 | 5.13 | End of Study | 5.13. End of Study Reasons for complete withdrawal from the study (including treatment and all follow-up visits) will occur under the following circumstances: - Patient withdrew consent - Death - Study termination by sponsor The patient may elect to withdraw from the study for reasons other than those listed above - an... | [] |
NCT03734016 | 5.14 | Lost to Follow-up | 5.14. Lost to Follow-up Every reasonable effort should be made to contact any patient lost to follow-up during the study to complete study-related assessments, record outstanding data, and retrieve study drug. Following unsuccessful telephone contact, an effort to contact the patient by mail using a method that provide... | [] |
NCT03734016 | 5.15 | Future Research (Optional) | 5.15. Future Research (Optional) Patients may optionally consent to use leftover or unused samples collected during this study for additional, future research purposes. No additional samples will be taken for future research purposes. Future research may include evaluation of additional potential biomarkers of response... | [] |
NCT03734016 | 6 | STUDY TREATMENT | 6. STUDY TREATMENT | [] |
NCT03734016 | 6.1 | Study Treatment Preparation and Dispensation | 6.1. Study Treatment Preparation and Dispensation | [] |
NCT03734016 | 6.1.1 | Packaging and Labeling | 6.1.1. Packaging and Labeling Zanubrutinib capsules will be provided in a child-resistant high-density polyethylene bottle with an induction seal and bottle label. Commercial supplies of ibrutinib will either be provided by the sponsor or directly purchased via local procurement by the site. Refer to the pharmacy manua... | [] |
NCT03734016 | 6.1.2 | Handling and Storage | 6.1.2. Handling and Storage The Interactive Response Technology (IRT) system will be used for drug supply management. Sponsor-supplied study drug(s) will be dispatched to a study center only after receipt of the required documents in accordance with applicable regulatory requirements and the sponsor's procedures. The i... | [] |
NCT03734016 | 6.1.3 | Study Drug Supply | 6.1.3. Study Drug Supply Zanubrutinib capsules will be provided by the sponsor. Ibrutinib will be provided via local procurement by the site. In limited circumstances, they may be provided by the sponsor. | [] |
NCT03734016 | 6.1.4 | Study Drug Dispensation Procedures | 6.1.4. Study Drug Dispensation Procedures Study drugs must be dispensed or administered according to procedures described herein. Only patients enrolled in the study may receive study drug(s), in accordance with all applicable regulatory requirements. Only authorized study center personnel may supply or administer stud... | [] |
NCT03734016 | 6.1.5 | Compliance and Accountability | 6.1.5. Compliance and Accountability Compliance will be assessed by the investigator and/or study personnel at each patient visit and information provided by the patient and/or guardian. The investigator and/or study personnel will keep accurate records of the quantities of study drug dispensed and used by each patient... | [] |
NCT03734016 | 6.1.6 | Disposal and Destruction | 6.1.6. Disposal and Destruction After completion of the study, and following final drug inventory reconciliation by the monitor, the study site will destroy or return all unused study drug supplies. The inventoried supplies can be destroyed on site or at the depot according to institutional policies after receiving wri... | [] |
NCT03734016 | 6.2 | Dosage and Administration | 6.2. Dosage and Administration | [] |
NCT03734016 | 6.2.1 | Zanubrutinib | 6.2.1. Zanubrutinib Zanubrutinib 160 mg will be taken twice a day with or without food. Patients will take zanubrutinib with water at approximately the same time every day, with a minimum of 8 hours between consecutive doses. Zanubrutinib capsules should not be opened, broken, or chewed at any time. In case of dose red... | [] |
NCT03734016 | 6.2.2 | Ibrutinib | 6.2.2. Ibrutinib Patients randomized to Arm B will receive ibrutinib. Ibrutinib should be administered per local prescribing guidelines (ie, Prescribing Information or Summary of Product Characteristics) and those guidelines should be followed throughout the study for these patients. The text below summarizes common cu... | [] |
NCT03734016 | 6.3 | Overdose | 6.3. Overdose Any dose of study drug in excess of that specified in this protocol is considered to be an overdose. Signs and symptoms of an overdose that meet any AE or SAE criterion must be reported in the appropriate time frame and documented as clinical sequelae to an overdose. There is no specific antidote for zanu... | [] |
NCT03734016 | 6.4 | Precautions | 6.4. Precautions For information on warnings and precautions for zanubrutinib, refer to the [Zanubrutinib](#page-86-10) [Investigator's Brochure.](#page-86-10) Additional information on the following precautions is detailed in this protocol: - Surgery and procedures (see Section [6.4.1\)](#page-50-3) - Dose modificatio... | [] |
NCT03734016 | 6.4.1 | Surgery and Procedures | 6.4.1. Surgery and Procedures Susceptibility to bleeding has been observed with BTK inhibitors. Study treatment with zanubrutinib should be held for 3 to 7 days before and after surgery, depending upon the type of surgery and the risk of bleeding. Study treatment with ibrutinib should follow local prescribing informati... | [] |
NCT03734016 | 6.5 | Dose Interruption and Modification | 6.5. Dose Interruption and Modification The guidelines below should be followed for dose interruption or modification of zanubrutinib or ibrutinib in the event of toxicities. The dose reduction guidance refers to an individual toxicity event (ie, successive thrombocytopenia events) and is not cumulative amongst differe... | [] |
NCT03734016 | 6.5.1 | Zanubrutinib | 6.5.1. Zanubrutinib The guidelines below should be followed for dose interruption or modification of zanubrutinib for hematologic (Section [6.5.1.1\)](#page-51-3) and non-hematologic (Section [6.5.1.2\)](#page-52-2) toxicities. | Toxicity occurrence | Dose level | Zanubrutinib dose (Arm A) | |---------------------|----... | [] |
NCT03734016 | 6.5.1.1 | Zanubrutinib Dose Reduction for Hematologic Toxicity | 6.5.1.1. Zanubrutinib Dose Reduction for Hematologic Toxicity Dosing will be held for individual patients under any of the following conditions, based on investigator assessment (using [Hallek M](#page-87-0) et al 2008) of study drug relatedness: - Grade 4 neutropenia (that is persistent for at least 10 consecutive day... | [] |
NCT03734016 | 6.5.1.2 | Zanubrutinib Dose Reduction for Non-hematologic Toxicity | 6.5.1.2. Zanubrutinib Dose Reduction for Non-hematologic Toxicity Guidelines for non-hematologic toxicities are given in [Table](#page-52-0) 3. For dose reductions, follow the guidance described in [Table](#page-51-2) 2. Table 3: Zanubrutinib Dose Reduction Steps for Nonhematologic Toxicity | Toxicity | Action for Zanu... | [] |
NCT03734016 | 6.5.1.3 | Zanubrutinib Dose Modifications When taking CYP Inhibitors and Inducers | 6.5.1.3. Zanubrutinib Dose Modifications When taking CYP Inhibitors and Inducers If strong/moderate CYP3A inhibitors and inducers are used during the trial (see Section [7.2.1\)](#page-58-1) follow the dose modifications in [Table](#page-53-1) 4. For use of prophylactic anti-infectives (ie, voriconazole) during screeni... | [] |
NCT03734016 | 6.5.2 | Ibrutinib | 6.5.2. Ibrutinib For dose modification of Ibrutinib, local prescribing guidelines appropriate for your country (ie, Prescribing Information or Summary of Product Characteristics) should be followed throughout the study. The information below uses one example of local prescribing guidelines, but local prescribing guidel... | [] |
NCT03734016 | 6.5.2.1 | Ibrutinib Dose Reduction for Hematologic Toxicity | 6.5.2.1. Ibrutinib Dose Reduction for Hematologic Toxicity Local prescribing guidelines should be followed for dose reductions related to hematologic toxicity. An example of common local prescribing guidelines is given here, but follow the local prescribing guidelines applicable to your country. Dosing will be held for... | [] |
NCT03734016 | 6.5.2.2 | Ibrutinib Dose Reduction for Non-Hematologic Toxicity | 6.5.2.2. Ibrutinib Dose Reduction for Non-Hematologic Toxicity Local prescribing guidelines should be followed for dose reductions related to non-hematologic toxicity. An example of common local prescribing guidelines is given here, but follow the local prescribing guidelines applicable to your country. Ibrutinib shoul... | [] |
NCT03734016 | 6.5.2.3 | Ibrutinib Dose Modifications When Taking CYP Inhibitors and Inducers | 6.5.2.3. Ibrutinib Dose Modifications When Taking CYP Inhibitors and Inducers Local prescribing guidelines should be followed for dose modifications related to CYP inhibitors and inducers. An example of common local prescribing guidelines is given here, but follow the local prescribing guidelines applicable to your cou... | [] |
NCT03734016 | 6.6 | Toxicity Management Recommendations | 6.6. Toxicity Management Recommendations Additional recommendations are provided in [Appendix](#page-108-0) 11 for the diagnosis and management of adverse events of interest (toxicity management). These recommendations are intended as guidance. [Appendix](#page-108-0) 11 should be used in conjunction with expert clinic... | [] |
NCT03734016 | 6.7 | Discontinuation from Study Treatment | 6.7. Discontinuation from Study Treatment Patients should discontinue study treatment for the following: - Withdrawal from the study (see Section [5.13\)](#page-46-1). - Pregnancy - The investigator or sponsor determines it is in the best interest of the patient - Intercurrent illness that compromises the patient's abi... | [] |
NCT03734016 | 7 | CONCOMITANT THERAPY | 7. CONCOMITANT THERAPY | [] |
NCT03734016 | 7.1 | Concomitant Therapy | 7.1. Concomitant Therapy All concomitant medications and herbal supplements taken during the study will be recorded in the eCRF with indication, dose information, and dates of administration. Patients with high tumor burden should be monitored closely, and prophylactic measures, including allopurinol or rasburicase, ma... | [] |
NCT03734016 | 7.1.1 | Permitted Medications | 7.1.1. Permitted Medications The following treatments are allowed: - Blood product transfusion and growth factor support per standard of care and institutional guidelines - Corticosteroids for non-CLL/SLL indications with the following restrictions: Patients should not receive treatment with systemic corticosteroids ot... | [] |
NCT03734016 | 7.1.2 | Prohibited Medications | 7.1.2. Prohibited Medications Patients should not receive other anticancer therapy (including but not restricted to chemotherapy, immunotherapy, corticosteroids for treatment of CLL, experimental therapy, radiotherapy, and herbal medications) during screening or while on treatment in this study. Other anticancer therap... | [] |
NCT03734016 | 7.2 | Potential Interactions Between the Study Drugs and Concomitant Medications | 7.2. Potential Interactions Between the Study Drugs and Concomitant Medications | [] |
NCT03734016 | 7.2.1 | CYP-Inhibiting/Inducing Drugs | 7.2.1. CYP-Inhibiting/Inducing Drugs | [] |
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