Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Adenocarcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Durvalumab

Antineoplastic Agents, Immunological

IV infusion q4w with 1500mg durvalumab until progressive disease

Jared Weiss, MD

The aims of the study are to monitor the long-term safety of durvalumab, to provide continued treatment or retreatment with durvalumab to eligible patients, and to collect overall survival (OS) information.

This is a multicenter, open-label, global study that will enroll patients who are currently receiving durvalumab monotherapy, or have previously received durvalumab as monotherapy or in combination with any other approved or investigational anticancer agents, in an eligible AstraZeneca/MedImmune-sponsored clinical study.

All involved know the identity of the intervention assignment.

Durvalumab Long-Term Safety and Efficacy Study

An Open-Label, Multi-Center, Global Study to Evaluate Long Term Safety and Efficacy in Patients Who Are Receiving or Who Previously Received Durvalumab in Other Protocols (WAVE)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment.

Type, frequency and severity of adverse events (including those treatment and post-treatment periods) will be listed according to CTCAE v5.0

The analysis of ORR will be based on investigator assessments using RECIST 1.1

The analysis of DOR will be based on investigator assessments using RECIST 1.1

Assessments of Overall Survival will be made at periodic time points until death

Iqvia Pty Ltd

Parexel

Medidata Solutions

CISCRP

AstraZeneca

Symptoms and General Pathology

Rare Diseases

Recurrence

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Hypofractionation guioded by dose painting

MAURO MI IORI, PhD

PATRIZIA PC CIAMMELLA, MD

Relapsed GBMs have a life expectancy of a few months and re-radiation has proven to be safe in terms of toxicity and effective in increasing OS. One of our studies \[Ciammella P, 2013, 8:222\] reported a median survival of 9.5 months in patients with recurrent GBM and treated with stereotactic radiotherapy with a total dose of 25 Gy in 5 consecutive sessions, in which the dose was prescribed to 70% isodose with a homogeneous gradient towards the center of the target volume. The identification with functional imaging of specific areas with higher tumor cell density, and the possibility of delivering precisely, thanks to the most advanced therapy units, different doses to the different sub-volumes, can lead to an increase in the maximum dose that can be delivered at the expense of the most aggressive areas (with a greater effect on the tumor), compared to smaller doses in areas with lower signal alteration. This selectivity of the doses should allow an increase in the efficacy of the therapy and therefore a hypothetical increase in local control, compared to a radio-induced toxicity on the surrounding healthy tissues almost comparable to that achieved with the previous hypofractionated treatments \[Ciammella P, 2013\]. In fact, delivering many high doses to the entire volume would result in an excess of radio-induced necrosis within the irradiated regions with high dose, as well as the impossibility of minimizing the doses on healthy areas and / or on non-neoplastic critical areas keeping them at internal dose ranges related to minimal and acceptable toxicity levels. Since there are no studies providing clear indications on the acute and late toxicity of irradiated healthy tissues that have already been the subject of a first course of radiotherapy (STUPP), the choice of safety is the primary objective of the study.

It is an exploratory, prospective, experimental, monocentric study. Having identified a main safety endpoint (toxicity of radiotherapy treatment) and in the absence of data currently available from previous studies and useful for sizing the sample, the sample is defined according to opportunity and feasibility criteria, (12 cases), with a drawing (3 cases + 3 cases + 6 cases) which provides for two intermediate safety assessment steps one month after the end of the third and sixth patient treatment. The study will be continued only in case of positive evaluation of both steps. For each individual patient the treatment is considered completed if: a) the experimental radiotherapy treatment has been completed; b) the first follow-up radiological assessment (NMR) was performed; c) the study treatment was prematurely interrupted due to lack of efficacy (documented disease progression) or unacceptable toxicity.

* Treatment: the treatment foreseen by the protocol foresees the planning and the execution of a hypofractionated radiotherapy (RT) treatment, administered in 5 daily sessions, with intensity modulated technique and inhomogeneous distribution of the dose guided by the diffusion images obtained with magnetic resonance (RM). The radiotherapy treatment must start within 7 days from the date of execution of the centering MRI which will include both the classic morphological sequences with administration of contrast medium and functional ones. In selected cases and according to clinical judgment it will be possible to request the revision of the anatomopathological and radiological findings.
* Radiation technique: for each patient, a radiotherapy treatment plan will be performed with conformed techniques such as intensity-modulated radiotherapy (IMRT) with dose redistribution: dose-painting.
* Positioning and immobilization of the patient: the patient must be treated in a supine position. The arms must be positioned along the body. The use of a knee support is recommended. The garment will be immobilized with a thermoplastic mask and corresponding neck rest supports.
* TC and planning RM: the planning CT should be acquired possibly with reduced layer thickness that contains the entire volume of the skull and the upper part of the shoulders. This is done to allow the possibility of planning non-coplanar type treatments. The last follow-up MRI, or the radiotherapy centering RM, composed of standard and functional sequences, is used for planning, in addition to those that the neuroradiologist will have considered useful to better characterize the clinical case under examination. More details on this are described in the Technical Annex.
* Target volume and organs at risk (OAR): the following target volumes must be identified: • Gross tumor volume (GTV): it is defined using and combining the conventional and advanced sequences of the NMR. • Planning target volume (PTV): it is represented by the GTV with three-dimensional expansion between 0 and 5 mm according to the problems highlighted during the tumor segmentation phase. See the Technical Annex in this regard.
* The following risky organs (OAR) must be identified: • Optical nerves: the definition of the related planning risk volume is also suggested (PRV: organ at risk with three-dimensional expansion; this margin must be chosen taking into account the acquisition thickness of the centering TC and the chosen GTV-PTV expansion margin). • chiasm. We also suggest the definition of the relative PRV (organ at risk with three-dimensional expansion; this margin must be chosen taking into account the acquisition thickness of the centering CT and the chosen GTV-PTV expansion margin). • retinas. We also suggest the definition of the relative PRV (organ at risk with three-dimensional expansion; this margin must be chosen taking into account the acquisition thickness of the centering CT and the chosen GTV-PTV expansion margin). Alternatively the eye globes can be surrounded. • Encefalic trunk.
* The following secondary OARs must be identified: • Lenses / Crystalline. We also suggest the definition of the relative PRV (organ at risk with three-dimensional expansion; this margin must be chosen taking into account the acquisition thickness of the centering CT and the chosen GTV-PTV expansion margin). • Healthy brain tissue. It is represented by the encephalon volume minus the PTV. • Screw. We also suggest the definition of the relative PRV (organ at risk with three-dimensional expansion; this margin must be chosen taking into account the acquisition thickness of the centering CT and the chosen GTV-PTV expansion margin).
* Dose prescription: i) Dose to the target: the prescription dose foresees a minimum dose of 30 Gy (6 Gy per session) for the areas with the highest ADC with a gradual increase in the dose of the lower ADC areas. The maximum hypothesized dose is 50 Gy, with a dose of 10 Gy per session to no more than 1cc of the irradiated brain tissue. The treatment plan, however, will be processed in the following order of priority: 1. Compliance with dose limits for primary OARs. 2. PTV coverage. 3. Compliance with dose limits for secondary OARs.
* Dose limits for primary risk organs: in the scientific literature there are various studies that indicate the dose limits of the organs at risk for brain radiation treatments.

Safety of IMRT Treatment With Inhomogeneous Dose in Patients With Relapsed High-grade Gliomas.

Safety of Intensity-modulated Radiotherapy Treatment With Inhomogeneous Dose Distribution in Patients With Relapsed High-grade Gliomas.

Evaluation of side effects in order to assess the risk / benefit ratio. Values greater than G3 according to the CTCAE v.4.0 scale will be considered adverse events.

Evaluation of the response rate according to the RANO criteria

Incidence of treatment-related radionecrosis measured with advanced magnetic resonance sequences.

Evaluation of survival in retreated patients

Health related QOL (HRQOL) evaluations using the EORTC QLQ-C30 (version 3) questionnaire. Raw scores will be transformed to a linear scale ranging from 0 to 100 (according to the standard EORTC) with a higher score representing a higher level for functioning or higher livel of symptomatology or problems.

\[N.W.Scott et al, Qual Life, 2009, 18:381-388\]

Brain cancer specific QOL evaluated by using the EORTC QLQ - BN20 questionnaire. Raw scores will be transformed to a linear scale ranging from 0 to 100 (according to the standard EORTC) with a higher score representing a higher level for functioning or higher livel of symptomatology or problems.

\[MJB Taphoorn et al, EJC, 2010, 46:1033-1040\]

Evaluation of disease progression in retreated patients

Arcispedale Santa Maria Nuova-IRCCS

Blood and Lymph Conditions

Immune System Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Ofatumumab

Eight once weekly infusions (1 x 300 mg + 7 x 2000 mg), then 2000 mg once monthly for two years

GSK Clinical Trials

The purpose of the trial is to investigate the efficacy and safety of ofatumumab retreatment and maintenance in patients with chronic lymphocytic leukemia who have previously responded or had disease stabilization after ofatumumab in an ongoing trial (Hx-CD20-406).

Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)

A Single-arm, International, Multi-center Trial Investigating the Efficacy and Safety of Ofatumumab Retreatment and Maintenance in CLL Patients Who Progressed Following Response or Stable Disease After Ofatumumab Treatment in Hx-CD20-406

Par. with complete remission (CR), nodular partial remission (nPR), and partial remission (PR) on 2 consecutive visits \>=56 days apart were classified as Rs; those with stable disease (SD)/progressive disease (PD) were classified as NRs. Per the NCIWG 1996 guidelines: CR; no lymphadenopathy/hepatomegaly/splenomegaly/constitutional symptoms, normal hematology, normocellular bone marrow sample for age, \<30% lymphocytes (LC), no lymphoid nodule; PR: \>=50% decrease in LC/lymphadenopathy; nPR: persistent bone marrow nodules; PD: new lesion or increase by \>=50% from baseline; SD: no CR, PR, or PD.

Duration of response is defined as the time from the initial response (first visit at which response is observed) to progression or death. If the participant had progression between scheduled visits, no progression at the end of the trial, treatment discontinuation for undocumented progression, treatment discontinuation for toxicity or other reason, new anti-cancer treatment, and experienced death or progression after two or more missed visits in a row the endpoint was censored.

PFS is defined as the time from randomization until progression (prog.)/death. Prog. events are defined by well-documented and verifiable data; other data are censored. If the par. had prog. between scheduled visits, died before the first assessment, or died between adequate visits, the endpoint was considered progressed. If there was no prog. at the end of the trial, treatment discontinuation for undocumented prog./toxicity/other reason, new anti-cancer treatment, and death/prog. after \>=2 missed visits in a row, the endpoint was censored. Clinical prog. is not considered as a prog. endpoint.

Time to next chronic lymphocytic leukemia (CLL) treatment is defined as the time from treatment allocation/randomization (Visit 2) until the time of the first administration of the next CLL treatment other than ofatumumab (or HuMaxCD20, a fully human monoclonal antibody to CD20 that is expressed on the surface of B-cells).

OS is defined as the time from allocation to death.

Reduction in tumor size was measured as the percent change in the sum of the products of the diameters of the largest abnormal lymph nodes from Baseline to Week 24. Percent change was calculated as (Week 24 SPD minus Baseline SPD)/Baseline SPD \* 100.

Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 12. Percent change was calculated as (Month 12 SPD minus Baseline SPD)/Baseline SPD \* 100.

Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 24. Percent change was calculated as (Month 24 SPD minus Baseline SPD)/Baseline SPD \* 100.

HAHAs are indicators of immunogenicity to ofatumumab. HAHA levels were assessed for each participant at the end of participation in the study (at their last visit). A positive HAHA status indicates a positive enzyme-linked immunosorbent assay (ELISA) result, an inconclusive status indicates a negative ELISA result at ofatumumab concentration above the threshold at which ofatumumab may interfere with the assay, and a negative status indicates a negative ELISA result at ofatumumab concentration below the threshold.

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. A list of AEs experienced in the study with a frequency threshold of 5% can be found in the AE section of this results record.

The data collected for this analysis are reported in the overall Serious Adverse Events (SAEs) of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.

The data collected for this analysis are reported in the overall SAEs of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.

Cmax is defined as the maximum concentration of drug in plasma samples (collected at the end of the infusion). Ctrough is defined as the concentration of drug in plasma samples at the end of a dosing interval (collected directly before next administration). Ctrough before the first infusion represents residual ofatumumab from participation in Study Hx-CD20-406.

Genmab

GlaxoSmithKline

SAEs and non-serious AEs were reported for members of the Safety Population, comprised of all participants randomized to treatment who received \>=1 dose of trial medication.

Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).

2000 mg Ofatumumab + DR

Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).

2000 mg Ofatumumab + BFR

Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).

2000 mg Ofatumumab + Other

Total

Age, Continuous

Sex: Female, Male

Asian

White

Race/Ethnicity, Customized

GSK Response Center

Responders with CR

Responders with nPR

Responders with PR

Non-responders with SD

Non-responders with PD

Full Analysis Set (FAS): all participants who had been exposed to study drug irrespective of their compliance to the planned course of treatment. Some participants were not evaluable (NE) due to participant withdraw, refusal, non-trial drug-related adverse events, and death.

Number of Participants (Par.) Classified as Responders (Rs) and Non-responders (NRs) for Objective Response in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines

Duration of Response

Progression-Free Survival (PFS)

Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment

Overall Survival (OS)

FAS. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 4. Only participants with a baseline value and a post-baseline value at Month 4 were included in the calculation.

Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 4

FAS. No participants in the 2000 mg Ofatumumab + Other treatment arm were able to contribute to this measure. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 12. Only participants with a baseline value and a post-baseline value at Month 12 were included in the calculation.

Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 12

FAS. No participants in the 2000 mg Ofatumumab + Other treatment arm were able to contribute to this measure. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 24. Only participants with a baseline value and a post-baseline value at Month 24 were included in the calculation.

Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 24

Screening, Positive, n=15 , 11, 1, 27

Screening, Inconclusive, n = 15 , 11 , 1, 27

Screening, Negative, n = 15 , 11 , 1, 27

Post-ofatumumab, Positive, n = 12 , 8 , 1, 21

Post-ofatumumab, Inconclusive, n=12 , 8, 1, 21

Post-ofatumumab, Negative, n =12 , 8, 1 , 21

This arm includes a total of all three arms combined.

FAS. During the study, samples were to be taken at the last visit; however, this may not have been possible, such as in cases of death, or when the visit was not obvious as the "last visit." Therefore, some samples were not available or were not collected.

Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab

Number of Participants Who Experienced Any Adverse Event

Number of Participants With the Indicated Major Infections

Number of Participants With Infections Requiring Hospitalization or Intravenous Antibiotics

Cmax Visit 2, n= 16, 11, 1, 28

Cmax Visit 14, n= 8, 5, 0, 13

Ctrough Visit 2, n= 16, 11, 1, 28

Ctrough Visit 14, n= 8, 5, 0, 13

FAS. Data are provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Cmax and Ctrough at Visit 2 (Week 0) and at Visit 14 (Month 4)

Overall Study

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Pharmaceutical Solutions

Anti-Infective Agents

Dexamethasone

Bortezomib

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Patients will start therapy with retreatment with 6 cycles of bortezomib and dexamethasone (two 21-day cycles followed by four 35-day cycles) followed by a second randomization in a 1:1 ratio to 1 of 2 prolonged therapy schedules with bortezomib alone (Group A1: once weekly for the first 4 weeks in 35-day cycles; or Group A2: once every other week)

Current Standard of Care: Patients will start retreatment with eight 21-day bortezomib and dexamethasone cycles, followed by posttreatment follow-up every 6 weeks.

Type= exact number, unit = mg/m2 body surface area, number = 1.3, form = powder for solution for injection, route = subcutaneous, injection on Days 1, 4, 8 and 11, every 21 days of cycle 1 and 2; injection on Days 1, 8, 15, 22, every 35 days for cycles 3 to 6; followed by injections on Days 1, 8, 15, 22 every 35 days (Group A1) or injections every other week (Group A2). Treatment will be stopped at confirmed disease progression

bortezomib (optimized retreatment)

Type= exact number, unit = mg, number = 20, form = tablet, route = oral, intake on Days 1, 2, 4, 5, 8, 9, 11 and 12, every 21 days of cycle 1 and 2; intake on Days 1, 2, 8, 9, 15, 16, 22 and 23 every 35 days for cycles 3 to 6

dexamethasone (optimized retreatment)

Type= exact number, unit = mg/m2 body surface area, number = 1.3, form = powder for solution for injection, route = subcutaneous, injection on Days 1,4,8,11, every 21 days for cycles 1 to 8 or until confirmed disease progression

bortezomib (standard retreatment)

Type = exact number, unit = mg, number = 20, form = tablet, route= oral, intake on Days 1, 2, 4, 5, 8, 9, 11, 12, every 21 days for cycles 1 to 8 or until confirmed disease progression

dexamethasone (standard retreatment)

The objective of this study is to describe the effect of optimized retreatment with bortezomib in combination with dexamethasone followed by prolonged therapy with bortezomib, versus standard retreatment with bortezomib in combination with dexamethasone on progression free survival (PFS).

This is an interventional, randomized (assignment to a group is happening by chance, like flipping a coin), open-label, parallel-group, event-driven, international, multicenter, Phase 3 study. This study has different phases: a pre-treatment phase, a treatment phase (which consists of an optimized retreatment period followed by a prolonged therapy period, or a standard retreatment period followed by a posttreatment period), and a long-term follow-up phase for survival up to the end of the study. Before the premature stopping of enrollment, the end of the study was event-driven, defined as 1 year after 186 events (an 'event' being defined as disease progression or death). Following the premature stopping of enrollment, effective 20 June 2014, the end of the study is defined as a maximum of 18 months after enrollment of the last patient in the study. After providing written informed consent, patients will be evaluated for eligibility during a 14-day pre-treatment period. The study doctor will carry out tests to see if the patient is suitable for this study, within the two weeks before receipt of the first dose of the study drugs. Once it has been determined that the patient is able to participate, he/she will be randomly assigned to 1 of 2 different bortezomib retreatment schedules. In this first randomization, patients will receive optimized retreatment or standard retreatment in a 2:1 ratio. Group A: optimized retreatment followed by prolonged therapy. Patients will start therapy with retreatment with 6 cycles of bortezomib and dexamethasone (two 21-day cycles followed by four 35-day cycles) followed by a second randomization in a 1:1 ratio to 1 of 2 prolonged therapy schedules with bortezomib alone (Group A1: once weekly for the first 4 weeks in 35-day cycles; or Group A2: once every other week). Group B: standard retreatment with eight 21-day bortezomib and dexamethasone cycles, followed by posttreatment follow-up every 6 weeks. During the retreatment phase, a series of tests will be done at the first day of each cycle. For patients in Group A the doctor will assess if the patient has responded to the treatment or not. Only if the patient responded, will he/she be able to continue in the prolonged therapy part of the study. At this time the patient will be randomized to one of the two groups (Group A1 or Group A2) in the prolonged therapy phase. During the prolonged therapy phase the disease status and the response to therapy will be evaluated every 6 weeks. This phase will continue until the disease progresses, in case there are unacceptable toxicities despite dose modifications. During the posttreatment period patients in group B will continue to be evaluated for disease status every 6 weeks until confirmed disease progression, when they start alternative multiple myeloma treatment, are withdrawn from the study, death or at the end of the study (a maximum of 18 months after the last patient is enrolled in the study), whichever occurs first. In case the patient discontinues bortezomib before disease progression during the treatment phase, he/she will be asked to complete the End of Study Visit procedures and will be evaluated every 6 weeks until confirmed disease progression, when they start alternative multiple myeloma treatment, are withdrawn from the study, death or at the end of the study (a maximum of 18 months after the last patient is enrolled in the study), whichever occurs first. All patients will have an End of Trial Visit performed 30 to 35 days after the last administration of bortezomib, or as soon as possible after bortezomib treatment is discontinued for patients receiving alternative multiple myeloma therapy. After confirmed disease progression or start of the first alternative multiple myeloma therapy, patients will enter the long-term follow-up phase for up to a maximum of 18 months after the last patient is enrolled in the study. During this phase, the patients will be contacted by at least a telephone call every other month to be followed up for the first alternative multiple myeloma therapy and survival. From the end of the study in countries where bortezomib is not commercially available for prolonged therapy or is not accessible (via a national program or access program) at that time, patients who in the opinion of the investigator would continue to benefit from prolonged therapy with bortezomib, will continue to be supplied with bortezomib until it is accessible in that particular country or for a period of 2 years, whichever occurs first. Before the premature stopping of enrollment, it was planned to enroll a target of 240 patients in this study.

Study to Evaluate Optimized Retreatment and Prolonged Therapy With Bortezomib

A Randomized, Controlled Phase 3 Study to Evaluate Optimized Retreatment and Prolonged Therapy With Bortezomib (Velcade) in Patients With Multiple Myeloma in First or Second Relapse.

Time from randomization to therapy to time of diagnosis of PD or death due to any cause

Overall response rate as defined by the combination of patients with complete response, very good partial response and partial response according to the International Myeloma Working Group 2011 criteria (IMWG)

Time to Progression is defined as the time from baseline to PD, discontinuation/withdrawal or death.

DOR is defined as the duration from the date of the best confirmed response for patients who achieved Complete Response (CR) or Partial Response (PR) to the date of first documented evidence of PD over the duration of the study.

The ECOG Performance Status is used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The score ranges from 0 "fully active, able to carry on all pre-disease performance without restriction" to 5 "dead".

The EORTC QLQ-C30 incorporates 5 functional scales (physical, role, emotional, cognitive and social functioning), 1 global health and quality of life scale, 3 symptom scales (fatigue, nausea/vomiting and pain), and 6 single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The recall period is 1 week (the past week). It is a 30-item questionnaire with responses ranging for the functional scales from not at all to very much and the global health/QOL ranging from very poor to excellent. Scores are transformed to 0-100 scale.

The EQ-5D is a 5-item questionnaire and a "thermometer" visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state)

Janssen-Cilag International NV

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, Follicular

Lymphosarcoma

Follicular Lymphoma

Antirheumatic Agents

Antibodies

Rituximab

Immunoglobulins

Galiximab

Immunologic Factors

galiximab (500 mg/m2 IV) in combination with rituximab (375 mg/m2 IV)once weekly for 4 weeks.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Durvalumab Long-Term Safety and Efficacy Study	NCT04078152	Solid Tumor	Durvalumab	18 Years - 130 Years	AstraZeneca
Safety of IMRT Treatment With Inhomogeneous Dose in Patients With Relapsed High-grade Gliomas.	NCT04610229	Glioblastoma Mu... Glioblastoma Glioblastoma, A...	Hypofractionati...	18 Years -	Arcispedale Santa Maria Nuova-IRCCS
Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)	NCT00802737	Leukaemia, Lymp...	Ofatumumab	18 Years -	GlaxoSmithKline
Study to Evaluate Optimized Retreatment and Prolonged Therapy With Bortezomib	NCT01910987	Multiple Myelom...	bortezomib (opt... dexamethasone (... bortezomib (sta... dexamethasone (...	18 Years -	Janssen-Cilag International NV
Retreatment Study of Galiximab + Rituximab in Follicular Non-Hodgkin's Lymphoma (NHL)	NCT00384150	Lymphoma, Non-H...	galiximab in co...	18 Years -	Biogen
Retreatment Study of Galiximab + Rituximab in Follicular Non-Hodgkin's Lymphoma (NHL)	NCT00384150	Lymphoma, Non-H...	galiximab in co...	18 Years -	Biogen
Study to Evaluate Optimized Retreatment and Prolonged Therapy With Bortezomib	NCT01910987	Multiple Myelom...	bortezomib (opt... dexamethasone (... bortezomib (sta... dexamethasone (...	18 Years -	Janssen-Cilag International NV
Safety of IMRT Treatment With Inhomogeneous Dose in Patients With Relapsed High-grade Gliomas.	NCT04610229	Glioblastoma Mu... Glioblastoma Glioblastoma, A...	Hypofractionati...	18 Years -	Arcispedale Santa Maria Nuova-IRCCS
Study of Chemotherapy Sequenced by or Combined With EGFR-TKIs for NSCLC Patients Failed to EGFR-TKIs Therapy	NCT01746277	Non Small Cell ...	combined group Sequenced group	18 Years - 75 Years	Peking Union Medical College Hospital

Spots Global Cancer Trial Database for retreatment

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

Spots Global Cancer Trial Database for retreatment

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

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