protocol_id stringclasses 263
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NCT03167242 | 9.7 | Interim assessments | 9.7 Interim assessments PK Run-in Part: For the patients in the PK Run-in KAF156 200 mg/LUM-SDF 960 mg cohort, PK analyses will be performed on the samples collected in the first 24 hours. AUC0-24, for KAF156 and lumefantrine will be calculated and compared with the expected values when one drug was given alone. Dosing... | [] |
NCT03167242 | 9.8 | Sample size calculation | 9.8 Sample size calculation
Sample size for PK run-in cohort The objective of this part is to assess the effect of LUM-SDF in the exposure of KAF156 in patients and to see if the current planned dosages for KAF156 in Part A should be modified or how to modify KAF156 dosages in Part A. Therefore, the sample size is cal... | [
"Sample size for PK run-in cohort",
"Part A",
"Part B"
] |
NCT03167242 | 10 | Ethical considerations | 10 Ethical considerations | [] |
NCT03167242 | 10.1 | Regulatory and ethical compliance | 10.1 Regulatory and ethical compliance This clinical study was designed and shall be implemented, executed and reported in accordance with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local regulations (including European Directive 2001/20/EC, United States (US) CFR 21, and Japan... | [] |
NCT03167242 | 10.2 | Informed consent procedures | 10.2 Informed consent procedures Eligible patients may only be included in the study after providing written (witnessed, where required by law or regulation), IRB/IEC-approved informed consent, or, if applicable after such consent has been provided by a legally acceptable representative(s) of the patient. In cases wher... | [] |
NCT03167242 | 10.3 | Responsibilities of the investigator and IRB/IEC | 10.3 Responsibilities of the investigator and IRB/IEC Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, written informed consent form, consent form updates, subject recruitment... | [] |
NCT03167242 | 10.4 | Publication of study protocol and results | 10.4 Publication of study protocol and results The key design elements of this protocol will be posted in a publicly accessible database such as clinicaltrials.gov. In addition, upon study completion and finalization of the study report the results of this trial will be either submitted for publication and/or posted in... | [] |
NCT03167242 | 10.5 | Quality Control and Quality Assurance | 10.5 Quality Control and Quality Assurance Novartis maintains a robust Quality Management (QM) system that includes all activities involved in quality assurance and quality control, including the assignment of roles and responsibilities, the reporting of results, and the documentation of actions and escalation of issue... | [] |
NCT03167242 | 11 | Protocol adherence | 11 Protocol adherence This protocol defines the study objectives, the study procedures and the data to be collected on study participants. Additional assessments required to ensure safety of patients should be administered as deemed necessary on a case by case basis. Under no circumstances is an investigator allowed to... | [] |
NCT03167242 | 11.1 | Protocol amendments | 11.1 Protocol amendments Any change or addition to the protocol can only be made in a written protocol amendment that must be approved by Novartis, health authorities where required, and the IRB/IEC prior to implementation. Only amendments that are intended to eliminate an apparent immediate hazard to patients may be i... | [] |
NCT03167242 | 12 | References | 12 References Ashley EA, Dhorda M, Fairhurst RM et al (2014) Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med;371(5):411-23. Dondorp AM, Nosten F, Yi P et al (2009) Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med.;361(5):455-67. Flegg JA, Guerin PJ, White NJ, et al (... | [] |
NCT03167242 | 13 | Appendix 1: Clinically notable laboratory and ECG values | 13 Appendix 1: Clinically notable laboratory and ECG values Certain adverse events should be considered medically significant and should be submitted to Novartis as SAEs within 24 hours.
1. Hepatic - ALT or AST > 5 × ULN ALP > 2 × ULN (in the absence of known bone pathology) TBL > 2 × baseline value - ALT or AST > 3 ×... | [
"1. Hepatic",
"2. Cardiac"
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NCT03167242 | 14 | Appendix 2: Liver event and Laboratory trigger Definitions and Follow-up Requirements | 14 Appendix 2: Liver event and Laboratory trigger Definitions and Follow-up Requirements Table 14-1 Liver event and laboratory trigger definitions | | Definition/ threshold | |---------------------------|--------------------------------------------------------------------------------------------------------------------... | [] |
NCT03167242 | 15 | Appendix 3: Cardiac Alert Threshold Values and Actions | 15 Appendix 3: Cardiac Alert Threshold Values and Actions Table 15-1 Cardiac alert threshold values and actions | | Values | Actions | |-------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------... | [] |
NCT03167242 | 16 | Appendix 4: Renal Alert Criteria and Actions | 16 Appendix 4: Renal Alert Criteria and Actions
Table 16-1 Specific renal alert criteria and actions | Serum Event | | | | |-------------------------------------------------------------|-----------------------------------------------------------|--|--| | Serum creatinine increase | Confirm 25% increase after 24-48h | ... | [
"Table 16-1 Specific renal alert criteria and actions",
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NCT03167242 | 17 | Appendix 5: | 17 Appendix 5: Table 17-1 Part A: KAF156 and LUM-SDF dosing scheme in case KAF156 relative exposure factor in PK Run-in vs. the reference mean AUC0-24h (4930 ng\h/mL) is available strengths | |--------|-----------|-----------|----------------|----------------------------------------------| | 1 | KAF156 | 400 | QD 1 day... | [] |
NCT03170882 | A | Phase 2, Randomized, Open-Label Study Comparing Oral Ixazomib/Dexamethasone and Oral Pomalidomide/Dexamethasone in Relapsed and/or Refractory Multiple Myeloma | A Phase 2, Randomized, Open-Label Study Comparing Oral Ixazomib/Dexamethasone and Oral Pomalidomide/Dexamethasone in Relapsed and/or Refractory Multiple Myeloma
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NCT03173248 | 1 | 6. 1. 1. P R O T O C O L A N D P R O T O C O L A M E N D M E N T S | 1 6. 1. 1. P R O T O C O L A N D P R O T O C O L A M E N D M E N T S A G 1 2 0 0 0 9 Pr ot oc ol v 1. 0 0 6 Ja nuar y 2 0 1 7 A me n d me nt 1, Versi o n 2. 0 ( 0 7 Fe br uar y 2 0 1 7) Gl o bal / S u m mar y of C ha n ges A me n d me nt 2, Versi o n 3. 0 ( 2 4 Marc h 2 0 1 7) Gl o b al / S u m mar y of C ha n ges A me... | [] |
NCT03173248 | C | LI NI C A L S T U D Y P R O T O C O L A G 1 2 0 0 0 9 | C LI NI C A L S T U D Y P R O T O C O L A G 1 2 0 0 0 9 A P h ase 3, M ultice nter, D o u ble Bli n d, R a n d o mize d, Pl ace b o C o ntr olle d St u d y of A G 1 2 0 i n C o m bi n ati o n wit h Az aciti di ne i n S u bjects ≥ 1 8 Ye ars of A ge wit h Pre vi o usl y U ntre ate d Ac ute M yel oi d Le u ke mi a wit h ... | [] |
NCT03173248 | C | O N FI D E N TI A L | C O N FI D E N TI A L | [] |
NCT03173248 | S | p o ns or si g n at ories | S p o ns or si g n at ories I, t he u n d ersi g ne d, h a ve rea d t he f ore g oi n g pr ot oc ol f or t he st u d y a n d a gree t o c o n d uct t he st u d y i n c o m plia nce wit h t he pr ot oc ol, G o o d Cli nical Practice, a n d t he a p plica ble re g ul at or y re q uire me nts.
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NCT03173248 | S | p o ns or si g n at ories | S p o ns or si g n at ories I, t he u n d ersi g ne d, h a ve rea d t he f ore g oi n g pr ot oc ol f or t he st u d y a n d a gree t o c o n d uct t he st u d y i n c o m plia nce wit h t he pr ot oc ol, G o o d Cli nical Practice, a n d t he a p plica ble re g ul at or y re q uire me nts.
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"N a me of S p o ns ... |
NCT03173248 | S | urviv al F oll o w u p | S urviv al F oll o w u p O nce t he st u d y is u n bli n de d, s ur vi val f oll o w u p will c o nti n ue. All s u bjects w h o are ali ve after a n E F S e ve nt will be c o ntacte d e ver y 8 wee ks f or s ur vi val f oll o w u p u ntil deat h, wit h dra wal b y s u bject, l oss t o f oll o w u p, or w he n t he S ... | [
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"A n al ysis f or t he P ri m ar y E n d p oi nt",
"Ke y ... |
NCT03173248 | S | af et y A n al yses: | S af et y A n al yses: Safet y will be e val uate d b y vital si g ns, t he res ults of E C O G P S, E C G, a n d E C H O or M U G A f or L V E F as cli nicall y i n dicate d ( met h o d per i nstit uti o nal sta n dar d of care, wit h t he sa me met h o d use d f or a n i n di vi d ual s u bject t hr o u g h o ut t he... | [
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NCT03173248 | S | u bjects wit h o ut re d uce d b aseli ne bl o o d c o u nts (ie, W B C c o u nt > 3. 0 1 0 / L, A N C > 1. 5 1 0 / L, a n d pl atelets > 7 5. 0 × 1 0 / L) pri or t o first tre at me nt: | S u bjects wit h o ut re d uce d b aseli ne bl o o d c o u nts (ie, W B C c o u nt > 3. 0 1 0 / L, A N C > 1. 5 1 0 / L, a n d pl atelets > 7 5. 0 × 1 0 / L) pri or t o first tre at me nt: If he mat ol o gic t o xicit y is o bser ve d f oll o wi n g azaciti di ne treat me nt, t he ne xt c ycl e of azaciti di ne t hera ... | [] |
NCT03173248 | S | u bjects wit h re d uce d b aseli ne bl o o d c o u nts (ie, W B C c o u nt ≤ 3. 0 × 1 0 / L or A N C ≤ 1. 5 1 0 / L or pl atelets ≤ 7 5. 0 × 1 0 / L) pri or t o tre at me nt: | S u bjects wit h re d uce d b aseli ne bl o o d c o u nts (ie, W B C c o u nt ≤ 3. 0 × 1 0 / L or A N C ≤ 1. 5 1 0 / L or pl atelets ≤ 7 5. 0 × 1 0 / L) pri or t o tre at me nt: F oll o wi n g azaciti di ne treat me nt, if t he decreas e i n W B Cs, A N C, or platelets fr o m t he val ue pri or t o treat me nt is less ... | [
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"9. 1 0. Ot her P ote nti al Ris ks",
"9. 1 0. ... |
NCT03173248 | T | a ble 1 2 C a us al Attri b uti o n G ui d a nce | T a ble 1 2 C a us al Attri b uti o n G ui d a nce | | Is t he a d verse e v e nt ( A E) s us pecte d t o be c a use d b y t he st u d y tre at me nt o n t he b asis of f acts, e vi de nce,scie nceb ase d r ati o n ales, a n d cli nic al j u d g me nt ? | | | |-------|---------------------------------------------------... | [
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NCT03173248 | W | O R L D M E DI C A L A S S O CI A TI O N D E C L A R A TI O N O F H E L SI N KI: | W O R L D M E DI C A L A S S O CI A TI O N D E C L A R A TI O N O F H E L SI N KI: Rec o m me n dati o ns G ui di n g Me dic al D oct ors i n Bi o me dical Researc h I n v ol vi n g H u ma n S u bjects A d o pte d b y t h e 1 8 t h W orl d Me dical Ass ociati o n ( W M A) Ge neral Asse m bl y, H elsi n ki, Fi nla n d, ... | [
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NCT03198728 | A | 12-Month, Randomized, Active-controlled, Open-label Study of the Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men | A 12-Month, Randomized, Active-controlled, Open-label Study of the Efficacy and Safety of Oral Testosterone Undecanoate in Hypogonadal Men 3URWRFRO1XPEHU 05678 (XGUD&71XPEHU 1RW\$SSOLFDEOH ,1&5HVHDUFK//&D6\QHRV +HDOWK&RPSDQ\ +HDOWK 6WXG\1XPEHU ,QYHVWLJDWLRQDO3URGXFW 629) 3KDVH 3KDVH 6SRQVRU 0DULXV3KDUPDFHXWLFDOV 6L[)RU... | [
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NCT03201965 | 6.2.3.1 | Preinfusion Medication | 6.2.3.1 Preinfusion Medication In an effort to prevent infusion-related reactions, all subjects will receive the following medications 1 to 3 hours prior to each daratumumab administration (1 hour prior to daratumumab administration is preferred): Preinfusion medications include the following: - Dexamethasone 20 mg IV ... | [] |
NCT03201965 | 6.2.3.2 | Postinfusion Medication | 6.2.3.2 Postinfusion Medication Consider administering low-dose oral methylprednisolone (≤20 mg) or equivalent, the day after the SC-infusion. However, if a background regimen-specific corticosteroid (eg, dexamethasone) is administered the day after the SC-infusion, additional postinfusion steroids are not required, bu... | [
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NCT03201965 | 6 | DOSAGE AND ADMINISTRATION | 6. DOSAGE AND ADMINISTRATION In this protocol, the term "study drug" refers to daratumumab only, and "study treatment" refers to daratumumab, cyclophosphamide, VELCADE (bortezomib), and dexamethasone. Treatment should be administered in the following order: - Treatment Arm A (CyBorD alone): dexamethasone first, then cy... | [] |
NCT03201965 | 6.1 | Treatment Cycles | 6.1. Treatment Cycles All cycles are 28-day cycles. Cycle 1 should begin within 72 hours of randomization. Each following cycle should begin 28 days after Day 1 of the previous cycle, with a 5-day window permitted to accommodate holidays, weekends, or other site scheduling concerns. If Day 1 of a cycle is delayed for m... | [] |
NCT03201965 | 6.2 | Daratumumab | 6.2. Daratumumab Detailed descriptions for preparation and SC-administration of daratumumab will be supplied in the Investigational Product Preparation Instructions (IPPI). | [] |
NCT03201965 | 6.2.1 | Treatment Schedule and Administration | 6.2.1. Treatment Schedule and Administration Daratumumab 1800 mg will be administered subcutaneously through a syringe by a manual push over approximately 5 minutes. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (Cycles 3-6), and then every 4 weeks until progr... | [] |
NCT03201965 | 6.2.2 | Dose Delays and Dose Modification | 6.2.2. Dose Delays and Dose Modification | [] |
NCT03201965 | 6.2.2.1 | Dose Modification | 6.2.2.1. Dose Modification No daratumumab dose modification (increase or decrease) will be permitted in response to toxicity. Dose delay is the only method for managing daratumumab-related toxicities. | [] |
NCT03201965 | 6.2.2.2 | Toxicity Management | 6.2.2.2. Toxicity Management If any of the following criteria are met, then all study treatment must be held to allow for recovery from toxicity. The criteria for a hold in study treatment (applicable to both arms) are: - Grade 4 hematologic toxicity (anemia, neutropenia or thrombocytopenia) - Grade 3 or higher thrombo... | [] |
NCT03201965 | 6.2.2.3 | Interruption or Missed Doses | 6.2.2.3. Interruption or Missed Doses A daratumumab dose held for more than 3 days from the per protocol administration date for any reason other than toxicities suspected to be related to daratumumab, or a delay of more than 5 days before the start of a new cycle, should be brought to the attention of the sponsor at t... | [] |
NCT03201965 | 6.2.3 | Guidelines for Prevention and Management of Daratumumab Infusion-related Reactions | 6.2.3. Guidelines for Prevention and Management of Daratumumab Infusion-related Reactions For the purpose of this protocol, infusion-related reactions (IRRs) are defined as systemic reactions related to the SC administration of the investigational agent. | [] |
NCT03201965 | 6.2.3.1 | Preinfusion Medication | 6.2.3.1. Preinfusion Medication In an effort to prevent infusion-related reactions, all subjects will receive the following medications 1 to 3 hours prior to each SC-daratumumab administration (1 hour prior to daratumumab administration is preferred): Preinfusion medications include the following: - Dexamethasone 20 mg... | [] |
NCT03201965 | 6.2.3.2 | Postinfusion Medication | 6.2.3.2. Postinfusion Medication Consider administering low-dose oral methylprednisolone (≤20 mg) or equivalent, the day after the SC- infusion. However, if a background regimen-specific corticosteroid (eg, dexamethasone) is administered the day after the SC-infusion, additional postinfusion steroids are not required, ... | [] |
NCT03201965 | 6.2.3.3 | Management of Infusion-Related Reactions | 6.2.3.3. Management of Infusion-Related Reactions Subjects should be observed during daratumumab SC-administration. Trained study staff at the clinic should be prepared to intervene in case of any IRRs and resources necessary for resuscitation (eg, agents such as epinephrine and aerosolized bronchodilator, also medical... | [] |
NCT03201965 | 6.2.3.3.1 | Infusion-Related Reactions of Grade 1 or Grade 2 | 6.2.3.3.1. Infusion-Related Reactions of Grade 1 or Grade 2 If the investigator assesses a Grade 1-2 IRR to be related to the daratumumab SC administration, then the administration of daratumumab should be paused. When the subject's condition is stable, daratumumab administration may be restarted at the investigator's ... | [] |
NCT03201965 | 6.2.3.3.2 | Infusion-Related Reactions of Grade 3 or Higher | 6.2.3.3.2. Infusion-Related Reactions of Grade 3 or Higher For SC-infusion-related AEs (other than laryngeal edema or bronchospasm) that are Grade 3, the daratumumab SC administration must be stopped and the subject must be observed carefully until resolution of the AE or until the intensity of the event decreases to G... | [] |
NCT03201965 | 6.2.3.3.3 | Recurrent Infusion-Related Reactions | 6.2.3.3.3. Recurrent Infusion-Related Reactions If a Grade 3 IRR (or Grade 2 or higher) event of laryngeal edema or bronchospasm recurs during or within 24 hours after a subsequent daratumumab SC-administration, daratumumab treatment must be discontinued. | [] |
NCT03201965 | 6.2.4 | Guidelines for Management of Daratumumab Administration-related Reactions | 6.2.4. Guidelines for Management of Daratumumab Administration-related Reactions For the purpose of this protocol, "administration-related reactions" are defined as localized reactions at the injection site (eg, erythema, local tenderness, swelling, etc). In Study MMY1004 Part 1, SC administration of daratumumab in abd... | [] |
NCT03201965 | 6.3 | Cyclophosphamide | 6.3. Cyclophosphamide Subjects will receive 300 mg/m2 cyclophosphamide as an oral or IV weekly dose (NOTE: maximum absolute weekly dose of cyclophosphamide is 500 mg, irrespective of body surface area [BSA]) (Days 1, 8, 15, 22) in every 28-day cycle for a maximum of 6 cycles. The amount (in mg) of cyclophosphamide to b... | [] |
NCT03201965 | 6.3.1 | Dose Adjustments for Cyclophosphamide | 6.3.1. Dose Adjustments for Cyclophosphamide Cyclophosphamide can cause myelosuppression (leukopenia, neutropenia, thrombocytopenia, or anemia), or bone marrow failure, or both. Monitoring of complete blood counts is essential during cyclophosphamide treatment so that the dose can be adjusted, if needed, according to [... | [] |
NCT03201965 | 6.3.2 | Urinary Tract and Renal Toxicity | 6.3.2. Urinary Tract and Renal Toxicity Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria have been reported with cyclophosphamide therapy. Bladder ulceration/necrosis, fibrosis/contracture, and secondary cancer may develop. Before starting treatment, it is necessary to exclude or correct any urinary tract obst... | [] |
NCT03201965 | 6.4 | Bortezomib | 6.4. Bortezomib Subjects will receive 1.3 mg/m2 bortezomib as an SC injection weekly (Days 1, 8, 15, 22) in every 28-day cycle for a maximum of 6 cycles. The amount (in mg) of bortezomib to be administered will be determined by BSA, calculated according to a standard nomogram ([Attachment](#page-118-1) 7). The total ca... | [] |
NCT03201965 | 6.4.1 | Dose Adjustments of Bortezomib | 6.4.1. Dose Adjustments of Bortezomib Dose adjustments should be based on the highest grade of toxicity that is ascribed to bortezomib. Bortezomib therapy should be withheld at the onset of any Grade 3 non-hematological or Grade 4 hematological toxicities excluding neuropathy as discussed in [Table 6](#page-62-6). Once... | [] |
NCT03201965 | 6.4.2 | Neurologic Toxicity | 6.4.2. Neurologic Toxicity If the subject experiences peripheral neuropathy, then dose adjustments should be made according to the recommendations in [Table 6](#page-62-6). Table 6: Recommended Dose Modification for Bortezomib-related Neuropathic Pain or Peripheral Sensory or Motor Neuropathy | Severity of Peripheral N... | [] |
NCT03201965 | 6.4.3 | Other Grade 3 or 4 Adverse Events | 6.4.3. Other Grade 3 or 4 Adverse Events For other Grade 3 or 4 toxicities judged by the investigator to be related to bortezomib alone, treatment with bortezomib should be interrupted and restarted at the next lower dose level once the toxicity has resolved to Grade 2 or less. For complete details on bortezomib, refer... | [] |
NCT03201965 | 6.5 | Dexamethasone | 6.5. Dexamethasone Dexamethasone will be administered at a total dose of 40 mg weekly (ie, Days 1, 8, 15, 22). On days of daratumumab dosing, subjects in Treatment Arm B will receive 20 mg on the day of daratumumab dosing as premedication and 20 mg on the day after daratumumab dosing. On weeks that daratumumab is not a... | [] |
NCT03201965 | 7 | TREATMENT COMPLIANCE | 7. TREATMENT COMPLIANCE Daratumumab and bortezomib will be administered by qualified site staff. Dexamethasone and cyclophosphamide will be administered by qualified site staff if given as an IV dose. The details of each administration will be recorded in the electronic case report form (eCRF). Subjects will be provide... | [] |
NCT03201965 | 8 | PRESTUDY AND CONCOMITANT THERAPY | 8. PRESTUDY AND CONCOMITANT THERAPY Throughout the study, investigators may prescribe any concomitant medications or treatments deemed necessary to provide adequate supportive care except for those listed in Section [8.3](#page-65-3). Systemic use of the following concomitant medications will be collected in the eCRF a... | [] |
NCT03201965 | 8.1 | Recommended Therapies | 8.1. Recommended Therapies | [] |
NCT03201965 | 8.1.1 | Prophylaxis for Pneumocystis carinii (jirovicii) | 8.1.1. Prophylaxis for Pneumocystis carinii (jirovicii) Pneumocystis carinii (jirovicii) pneumonia prophylaxis is recommended, as per institutional guidelines. | [] |
NCT03201965 | 8.1.2 | Prophylaxis for Herpes Zoster Reactivation | 8.1.2. Prophylaxis for Herpes Zoster Reactivation Prophylaxis for herpes zoster reactivation as per local standard of care is recommended during the Treatment Phase. Acceptable antiviral therapy includes acyclovir (eg, 200 mg given orally 3 times a day, or 400 mg given orally 2 times a day or per institutional standard... | [] |
NCT03201965 | 8.1.3 | Prophylaxis or Management of Hemorrhagic Cystitis | 8.1.3. Prophylaxis or Management of Hemorrhagic Cystitis Medications used to treat hemorrhagic cystitis, including but not limited to mannitol, Mesna, normal saline hydration, are permitted during the study. | [] |
NCT03201965 | 8.1.4 | Management of Hepatitis B Virus Reactivation | 8.1.4. Management of Hepatitis B Virus Reactivation Primary antiviral prophylaxis is permitted as per local standard of care. Per protocol, HBV DNA testing by PCR is mandatory for subjects at risk for HBV reactivation see Section [9.9.](#page-79-2) For subjects who are diagnosed with HBV reactivation while on treatment... | [] |
NCT03201965 | 8.1.5 | Management of Peripheral Edema, Pulmonary Edema, Congestive Heart Failure. | 8.1.5. Management of Peripheral Edema, Pulmonary Edema, Congestive Heart Failure. Patients with AL amyloidosis are prone to volume overload secondary to their underlying illness and secondary to the administration of dexamethasone, which may also cause peripheral edema. The subject will have weight assessments as descr... | [] |
NCT03201965 | 8.2 | Permitted Therapies | 8.2. Permitted Therapies In addition, subjects are to receive full supportive care. The following medications and supportive therapies are examples of support therapies that may be used during the study: - Antiviral, antibacterial, and antifungal medications - Colony stimulating factors, erythropoietin, and transfusion... | [] |
NCT03201965 | 8.3 | Prohibited Therapies During the First 6 Cycles of Therapy | 8.3. Prohibited Therapies During the First 6 Cycles of Therapy Concomitant administration of any other therapy for the intention of treating AL Amyloidosis is prohibited including medications that target CD38. Concurrent use of corticosteroids is prohibited, unless subjects are on chronic steroids (maximum dose 20 mg/d... | [] |
NCT03201965 | 9 | STUDY EVALUATIONS | 9. STUDY EVALUATIONS | [] |
NCT03201965 | 9.1 | Study Procedures | 9.1. Study Procedures | [] |
NCT03201965 | 9.1.1 | Overview | 9.1.1. Overview The Time and Events Schedule ([Table](#page-25-2) 1) summarizes the frequency and timing of measurements applicable to this study. Study assessments will be performed only after written informed consent is obtained. It is acceptable to obtain informed consent before the first day of the Screening Phase.... | [] |
NCT03201965 | 9.1.1.1 | Bone Marrow Biopsy/Aspirate Considerations | 9.1.1.1. Bone Marrow Biopsy/Aspirate Considerations Three unstained formalin fixed paraffin embedded (FFPE) slides from the bone marrow biopsy or 2 unstained slides and 1 hematoxylin and eosin (H&E)-stained slide should be sent to the central laboratory to assess CD38 expression on the plasma cells. These slides may be... | [
"Bone Marrow Aspirate to be Obtained at Complete Hematologic Response"
] |
NCT03201965 | 9.1.2 | Screening Phase | 9.1.2. Screening Phase The signed ICF must be obtained before any study-specific procedures are performed. Routine procedures performed as standard of care can be used for the study and do not need to be repeated if performed within the specified screening window. The Screening Phase begins when the first screening pro... | [] |
NCT03201965 | 9.1.2.1 | Histopathological Diagnosis of Amyloidosis | 9.1.2.1. Histopathological Diagnosis of Amyloidosis Tissue Specimens: based on detection of homogenous amorphous, eosinophilic, hyaline-like, extracellular (subepithelial) material by light microscopy of a hematoxylin and eosin stained biopsy (4-6µ thick sections) and concomitant congo red staining (organophilic/eosino... | [
"Mass Spectrometry Typing of AL Amyloid (Liquid Chromatography-Tandem Mass Spectrometry [LC-MS/MS]):"
] |
NCT03201965 | 9.1.2.2 | Factor X Deficiency | 9.1.2.2. Factor X Deficiency Subjects with AL amyloidosis may develop acquired factor X deficiency (Choufani 2001).[5](#page-109-14) Testing coagulation parameters and factor X levels for all subjects is recommended if a subject will have an invasive procedure, but not required. Any clinically significant bleeding shou... | [] |
NCT03201965 | 9.1.3 | Treatment Phase | 9.1.3. Treatment Phase Details of the procedures performed during the Treatment Phase are outlined in the Time and Events Schedule ([Table](#page-25-2) 1). Subjects should start study treatment within 72 hours after randomization. Subjects will be closely monitored for AEs, laboratory abnormalities, and clinical respon... | [] |
NCT03201965 | 9.1.3.1 | Safety Run-In | 9.1.3.1. Safety Run-In Subjects in the safety run-in will receive daratumumab plus CyBorD, with dosing staggered by at least 48 hours between subjects. After at least 10 subjects in the run-in have had at least 1 cycle of study treatment, an analysis of safety will be conducted by the sponsor and external academic hema... | [] |
NCT03201965 | 9.1.3.2 | Randomized Study | 9.1.3.2. Randomized Study For subjects in Treatment Arm A, treatment will be from Cycle 1 to Cycle 6. Thirty days after the end of Cycle 6, subjects will have an End-of-Treatment visit and then enter the Post-Treatment Observation Phase. For subjects in Treatment Arm B, combination treatment will be from Cycle 1 to Cyc... | [] |
NCT03201965 | 9.1.3.3 | Autologous Stem Cell Collection Considerations | 9.1.3.3. Autologous Stem Cell Collection Considerations Stem cell collection is permitted during the study. Granulocyte colony-stimulating factor or plerixafor may be used as mobilization agents. Additional cyclophosphamide may also be used for mobilization. Investigators will record details of the stem cell yield (num... | [] |
NCT03201965 | 9.1.4 | End-of-Treatment | 9.1.4. End-of-Treatment The end-of-treatment is defined as any of the following: - Completion of 6 cycles of CyBorD in Treatment Arm A - Completion of 24 cycles (~2 years) of daratumumab treatment in Treatment Arm B - Meeting any criterion in the MOD-PFS endpoint at any time (see Section [2.2](#page-40-1) for definitio... | [] |
NCT03201965 | 9.1.4.1 | Subsequent Therapy | 9.1.4.1. Subsequent Therapy If a subject starts subsequent therapy prior to meeting the MOD-PFS endpoint, disease assessments should continue as scheduled until disease progression per the MOD-PFS endpoint has been recorded. In addition, collection of PRO data will occur when subsequent therapy is started and continue ... | [] |
NCT03201965 | 9.1.4.2 | End-of-Treatment Visits | 9.1.4.2. End-of-Treatment Visits Unless a subject withdraws consent for study participation or is lost to follow-up, an End-of-Treatment visit is to occur 30 days (±3 days) after the last dose of study treatment, or as soon as possible before the start of subsequent therapy. Every effort should be made to conduct the E... | [] |
NCT03201965 | 9.1.5 | Post-Treatment Observation Phase and Long-Term Follow-up | 9.1.5. Post-Treatment Observation Phase and Long-Term Follow-up For subjects who discontinue study treatment before disease progression has been observed, disease evaluations should continue to be performed in the Post-Treatment Observation Phase as specified in the Time and Events Schedule ([Table](#page-25-2) 1). Sub... | [] |
NCT03201965 | 9.2 | Efficacy Evaluations | 9.2. Efficacy Evaluations Disease response and progression will be based on assessments for hematologic response as defined in Section [9.2.1](#page-72-2). A blinded IRC consisting of 3 experts in AL amyloidosis will evaluate and adjudicate responses. The investigator should also continue to evaluate responses locally ... | [] |
NCT03201965 | 9.2.1 | Hematologic Response Categories | 9.2.1. Hematologic Response Categories Disease evaluations must be performed on the scheduled assessment day (±5 days) every 4 weeks during Cycles 1 through 6 and every 8 weeks at Cycle 7 and beyond (including during the Post-Treatment observation phase) until MOD-PFS is observed. If study treatment has been delayed fo... | [] |
NCT03201965 | 9.2.2 | Monoclonal Protein (M-protein) Measurements in Serum and Urine | 9.2.2. Monoclonal Protein (M-protein) Measurements in Serum and Urine Blood and 24-hour urine samples for M-protein measurements will be sent to and analyzed by a central laboratory. Only 1 serum and one 24-hour urine sample per time point are required by the central laboratory to perform the following tests. If the 24... | [] |
NCT03201965 | 9.2.3 | Determination of Organ Response | 9.2.3. Determination of Organ Response Organ disease that is considered to be quantifiable for response evaluated by the central laboratory includes cardiac disease (NT-proBNP, troponin T, and high sensitivity troponin T), renal disease (proteinuria, eGFR), and hepatic disease (alkaline phosphatase). Cardiac and liver ... | [] |
NCT03201965 | 9.2.4 | Bone Marrow Assessment | 9.2.4. Bone Marrow Assessment Bone marrow biopsy slides will be assessed by IHC for CD38 expression on the plasma cells and bone marrow aspirate slides will be used to identify an index clone(s) for baseline MRD assessment. MRD assessment has been shown to have prognostic significance in many hematological malignancies... | [] |
NCT03201965 | 9.3 | Pharmacokinetics and Immunogenicity | 9.3. Pharmacokinetics and Immunogenicity | [] |
NCT03201965 | 9.3.1 | Evaluations | 9.3.1. Evaluations Samples to assess both the serum concentration (pharmacokinetics) of daratumumab and the generation of anti-daratumumab antibodies (immunogenicity) will be obtained from all subjects in the safety run-in and in Treatment Arm B according to the Time and Events Schedule ([Table](#page-25-2) 1 and [Tabl... | [] |
NCT03201965 | 9.3.2 | Analytical Procedures | 9.3.2. Analytical Procedures Serum samples will be analyzed to determine concentrations of daratumumab or generation of antibodies to daratumumab using validated immunoassay methods by or under the supervision of the sponsor's bioanalytical facility. For the daratumumab immunogenicity assessments, serum samples will be... | [] |
NCT03201965 | 9.3.3 | Pharmacokinetic Parameters | 9.3.3. Pharmacokinetic Parameters Pharmacokinetic samples to determine serum concentration of daratumumab will be obtained from subjects in Treatment Arm B. The pharmacokinetic parameters are defined as: - Sample collected on Day 4 will be nominally classified as Cmax: Maximum observed serum concentration - Predose sam... | [] |
NCT03201965 | 9.3.4 | Immunogenicity Assessments | 9.3.4. Immunogenicity Assessments Serum from venous blood samples collected from all subjects in the safety run-in and Treatment Arm B will be assessed for the generation of anti-daratumumab antibodies (immunogenicity) according to the Time and Events Schedule. Daratumumab concentration will be evaluated at all immunog... | [] |
NCT03201965 | 9.4 | Pharmacokinetic/Pharmacodynamic Evaluations | 9.4. Pharmacokinetic/Pharmacodynamic Evaluations Data permitting, pharmacokinetic/pharmacodynamic modeling may be performed, to assess the relationship between serum concentrations of daratumumab and endpoints of clinical efficacy or safety. If these analyses are performed, then the details and results will be presente... | [] |
NCT03201965 | 9.5 | Biomarkers | 9.5. Biomarkers Biomarker analyses are dependent upon the availability of appropriate biomarker assays and may be deferred or not performed if during or at the end of the study it becomes clear that the analysis will have no scientific value, or if there are not enough samples or not enough responders to allow for adeq... | [] |
NCT03201965 | 9.6 | Sample Collection and Handling | 9.6. Sample Collection and Handling The actual dates and times of local sample collection must be recorded in the eCRF or laboratory requisition form. If blood samples are collected via an indwelling cannula, then an appropriate amount (1 mL) of serosanguineous fluid slightly greater than the dead space volume of the l... | [] |
NCT03201965 | 9.7 | Medical Resource Utilization | 9.7. Medical Resource Utilization Medical resource utilization data, associated with protocol-driven medical encounters and safety monitoring, will be collected in the eCRF by the investigator and study-site personnel for all subjects throughout the study. Specifically, the investigator will document all hospitalizatio... | [] |
NCT03201965 | 9.8 | Patient-Reported Outcomes | 9.8. Patient-Reported Outcomes On the days that PROs are scheduled (see [Table](#page-25-2) 1), the PROs should be administered before any other study procedures. If a subject has completed the PRO assessments and dosing is delayed, the PRO assessment does not need to be repeated if the assessment occurs ≤4 days before... | [] |
NCT03201965 | 9.9 | Safety Evaluations | 9.9. Safety Evaluations Safety will be assessed by AEs, laboratory test results, ECGs, echocardiograms, vital sign measurements, physical examination findings, and ECOG performance status. Any clinically relevant changes occurring during the study must be recorded on the Adverse Event section of the eCRF. Any clinicall... | [
"Adverse Events",
"Clinical Laboratory Tests",
"The following tests will be performed by the local laboratory:",
"Hematology Panel",
"Serum Chemistry Panel",
"HBV Serology",
"Hepatitis B Virus (HBV) DNA Tests",
"The following tests will be performed by the central laboratory and results made available... |
NCT03201965 | 10 | SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL FROM THE STUDY | 10. SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL FROM THE STUDY | [] |
NCT03201965 | 10.1 | Completion | 10.1. Completion A subject will be considered to have completed the study if he or she has died before the end of the study, has not been lost to follow-up, or has not withdrawn consent for study participation before the end of the study (end of study defined in Section [17.9.1\)](#page-106-4). | [] |
NCT03201965 | 10.2 | Discontinuation of Study Treatment/Withdrawal from the Study | 10.2. Discontinuation of Study Treatment/Withdrawal from the Study
Discontinuation of Study Treatment A subject will not be automatically withdrawn from the study if they must discontinue treatment before the end of the treatment regimen. The End-of-Treatment visit and Post-Treatment visit assessments should continue ... | [
"Discontinuation of Study Treatment",
"Withdrawal From the Study"
] |
NCT03201965 | 11 | STATISTICAL METHODS | 11. STATISTICAL METHODS Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general description of the statistical methods to be used to analyze the efficacy and safety data is outlined below. Specific details will be provided in the Statistical Analysis Plan. | [] |
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