Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Daratumumab

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

IBERDEX

* Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO).
* Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO.

IBERDARADEX

* Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, PO.
* Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO.
* Daratumumab will be given at 1800 mg, every 4 weeks, subcutaneously (SC). Cycles 1 and 2 (C1 and C2): Days 1, 8, 15, and 22 C3-6: Days 1 and 15 From C7 onwards: Day 1 of each cycle Cycles will be of 4 weeks of duration (28 days).

Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO)

Iberdomide

Dexamethasone 40 mg (PO) (or 20 mg (PO) if patient ≥ 75 years old) should be administered on the days 1, 8, 15 and 22 of every 4-week cycle.

Daratumumab will be given at 1800 mg, every 4 weeks, subcutaneously (SC). Cycles 1 and 2 (C1 and C2): Days 1, 8, 15, and 22 C3-6: Days 1 and 15 From C7 onwards: Day 1 of each cycle Cycles will be of 4 weeks of duration (28 days).

Carmen López-Carrero

Roberto Maldonado

Sunil Lakhwani

Cristina Encinas Rodríguez

Joaquín Martínez López

Joan Bargay Llenonart

Paula Rodríguez Otero

Maria Victoria Mateos Manteca

Enrique Ocio San Miguel

Marta Reinosa Segura

Javier de la Rubia Comos

María Victoria Mateos Manteca

Verónica González de la Calle

Jesús San Miguel Izquierdo

Juan José Lahuerta Palacios

Joan Bladé Creixenti

This is a multicenter, phase II, national, and open-label study to evaluate the efficacy and safety of two different combinations, iberdomide-dexamethasone (IBERDEX) and iberdomide-dexamethasone in combination with daratumumab (IBERDARADEX) in transplant ineligible newly diagnosed multiple myeloma (NDMM) patients. It will be ensured that at least 30% of the patients are frail in order to evaluate the feasibility of these combinations in this special population.

Patients will receive treatment with either iberdomide + dexamethasone (IBERDEX) or iberdomide + daratumumab + dexamethasone (IBERDARADEX), until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first. This is not a randomized trial so eligible patients will be sequentially allocated to receive iberdomide-dexamethasone or iberdomide-dexamethasone plus daratumumab.

This is a multicenter, phase II, national, and open-label study to evaluate the efficacy and safety of two different combinations, iberdomide-dexamethasone (IBERDEX) and iberdomide-dexamethasone in combination with daratumumab (IBERDARADEX) in transplant ineligible newly diagnosed multiple myeloma (NDMM) patients. It will be ensured that at least 30% of the patients are frail in order to evaluate the feasibility of these combinations in this special population.

Patients will receive treatment with either iberdomide + dexamethasone (IBERDEX) or iberdomide + daratumumab + dexamethasone (IBERDARADEX), until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first. This is not a randomized trial so eligible patients will be sequentially allocated to receive iberdomide-dexamethasone or iberdomide-dexamethasone plus daratumumab.

Participants will be evaluated for study eligibility per protocol as defined in the Inclusion/Exclusion criteria . The screening period takes place 28 days prior to the baseline visit.

Frontline treatment: cohorts 1 and 2

Cohort 1: IBERDEX

* Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO).
* Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO.

Cohort 2: IBERDARADEX

* Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, PO.
* Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO.
* Daratumumab will be given at 1800 mg, every 4 weeks, subcutaneously (SC). Cycles 1 and 2 (C1 and C2): Days 1, 8, 15, and 22 C3-6: Days 1 and 15 From C7 onwards: Day 1 of each cycle

The study treatment in both cohorts will be until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first.

The trial has the following objectives:

Primary Objectives

PO1: To determine the efficacy of iberdomide in combination with dexamethasone (IBERDEX cohort 1) and also in combination with daratumumab and dexamethasone (IBERDARADEX cohort 2) in transplant ineligible NDMM patients, as measured by overall response rate (ORR) as well as the other response categories and especially the complete response rate (CRR) according to the International Myeloma Working Group (IMWG) response criteria 2016.

Secondary Objectives

SO1: To evaluate the efficacy in terms of minimal residual disease (MRD) with especial attention to the proportion of patients in MRD negative at 12 months of starting treatment as well as patients able to sustain it over time (according to the IMWG response criteria 2016).

SO2: To evaluate time to event data in the overall population and in the frail and non-frail population: Progression Free Survival (PFS) (from the time of inclusion in the trial until progression and/or death) and Overall Survival (OS).

SO3: To evaluate the changes in the immune profiling in order to better understand the outcomes in the overall population and in the non-frail and frail subgroups of patients.

SO4: To assess quality of life evolution through EQ-5D/5L, QLQ-C30 and MY20 questionnaires, at baseline and at months 4, 8, 12, 18, and 24.

SO5: To assess the safety of the combination of iberdomide + dexamethasone and iberdomide + dexamethasone + daratumumab.

Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.

Multicenter, Phase II, National and Open-label Study to Evaluate Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.

The percentage of participants with a confirmed partial response (PR) or better (PR, Very good partial response (VGPR), Complete response (CR), stringent complete response (sCR)).Response rates will be monitored monthly, but the study will report the % of patients achieving CR rate at month 12, 18, 24 and yearly thereafter.

The percentage of participants with a confirmed complete response (CR) or better (stringent complete response (CR, sCR).

The percentage of participants who are MRD negative by next-generation flow cytometry (NGF), PET/CT, and mass spectrometry.

Time from the date of randomization until the earliest date of documented disease progression or death due to any cause.

Time from the date of randomization until the date of death due to any cause

Relative distribution and immunophenotype of inmune profiling from baseline onto treatment, remission and disease progression.

Global health status/quality of life based on patient reported outcome: EQ-5D/5L questionnaire.

Global health status/quality of life based on patient reported outcome: QLQ-C30 questionnaire.

Global health status/quality of life based on patient reported outcome: MY20 questionnaire.

Incidence of deaths and primary cause of death for safety analysis.

Percentage of patients discontinuing therapy due to AEs.

Percentage of patients requiring dose modifications.

Percentage of patients with changes in laboratory analytes from the hematology and blood chemistry panel.

Celgene-BMS

Janssen-Cilag, S.A.

LIDESEC

PETHEMA Foundation

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphatic Diseases

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Bendamustine Hydrochloride

Rituximab

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Rituximab (RTX)

Tafasitamab: Tafasitamab dose: 12 mg/kg intravenously (IV)

Tafasitamab

Bendamustine (BEN)

The purpose of the study is to compare the safety and efficacy of Tafasitamab with BEN versus RTX with BEN in adult patients with relapsed of refractory DLBCL.

This is a randomised, two-arm, multicentre, open-label phase II/III efficacy and safety study of Tafasitamab in combination with BEN versus RTX in combination with BEN given to adult patients who have relapsed after or are refractory to at least one but no more than three prior systemic therapies and have failed, or are not candidates for HDC and ASCT, and have thus exhausted their therapeutic options of demonstrated clinical benefit. At least one prior therapy line must have included a CD20-targeted therapy.

Outcome assessor: blinding on treatment group

A Trial to Evaluate the Efficacy and Safety of Tafasitamab With Bendamustine (BEN) Versus Rituximab (RTX) With BEN in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

A Phase 2/3, Randomised, Multicentre Study of Tafasitamab With Bendamustine Versus Rituximab With Bendamustine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL) Who Are Not Eligible for High-Dose Chemotherapy (HDC) and Autologous Stem-Cell Transplantation (ASCT)

To determine the efficacy of a combination of MOR00208 with BEN versus a combination of RTX with BEN in terms of progression-free survival (PFS) in:

* Adult patients with R-R DLBCL (overall population)
* A subgroup of adult patients with R-R DLBCL with low baseline peripheral blood NK-cell count (NKCC-low)

Number of participants with treatment- and non-treatment related adverse events as assessed by CTCAE

EORTC QLQ-C30 and EQ-5D-5L questionnaires will be used

ICON Clinical Research

MorphoSys AG

Prednisone

Melphalan

Lenalidomide

Bortezomib

Angiogenesis Inhibitors

Growth Inhibitors

Immunosuppressive Agents

Velcade (V):

* 1.3 mg/m2 subcutaneously on days 1, 4, 8, 11, 22, 25, 29 and 32 in cycles 1-4;
* 1.3 mg/m2 subcutaneously on days 1, 8, 22 and 29 from cycle 5.

Melphalan (M):

- 9 mg/m2 orally on days 1, 2 3 and 4 of each cycle.

Prednisone (P):

- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Each cycle is a 42-day cycle. Duration: Maximum 9 cycles can be performed.

Lenalidomide (R):

-25 mg orally on days 1-21 of each cycle.

Dexamethasone (d):

-40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycle. Duration: until PD or intolerance.

Velcade (V):

- 1.3 mg/m2 subcutaneously twice weekly on weeks 1, 2, 4, and 5 of cycle 1 (days 1,4,8,11,22,25,29,32) and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9 (days 1,8,22,29).

Melphalan (M):

- 9 mg/m2 orally on days 1, 2, 3 and 4 of each cycle.

Prednisone (P):

- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle.

Daratumumab:

-16 mg per kilogram of body weight or 1800 mg Daratumumab subcutaneous (SC) (according to local clinical practice) with oral or intravenous dexamethasone (to manage infusion reactions) at a dose of 20 mg once weekly in cycle 1 (days 1,8,15,22,29,36), every 3 weeks in cycles 2 through 9 (days 1,22), and every 4 weeks thereafter until disease progression or unacceptable toxic effects. Dexamethasone at a dose of 20 mg was substituted for prednisone on day 1 of each cycle.

Lenalidomide (R):

- 25 mg orally on days 1-21 of each cycle.

Dexamethasone (d):

- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycles.

Daratumumab:

-intravenous at a dose of 16 mg per kilogram of body weight or 1800 mg Daratumumab subcutaneous (SC) (according to local clinical practice) once weekly during cycles 1 and 2, every 2 weeks during cycles 3 through 6, and every 4 weeks thereafter; preinfusion medications were administered approximately 1 hour before each daratumumab dose.

Velcade

Alessandra Larocca, Dott.ssa

Multiple myeloma (MM) is a neoplastic disease deriving from an abnormal proliferation of monoclonal plasma cells in the bone marrow. The survival of MM patients varies from less than 6 months to more than 10 years depending on the stage of disease at diagnosis and prognostic factors. Before 2021, in Italy three current standard treatments were approved for elderly or younger patients with significant comorbidities not eligible for autologous stem cell transplantation (ASCT): bortezomib-melphalan-prednisone (VMP), melphalan-prednisone-thalidomide (MPT) and lenalidomide with low-dose dexamethasone (Rd). Daratumumab is a human IgGk monoclonal antibody that targets CD38, that showed clinical benefit in combination with standard-of-care therapy. The addition of Daratumumab (Dara) to VMP and Rd has created two new standards-of-care regimens Dara-VMP and Dara-Rd, which were approved by the EMA in October 2019, and by the AIFA at the beginning of 2021, based on the results of two large phase 3 studies.

A consistent fraction of elderly patients with cancer and co-morbidities are at increased risk of developing frailty (an emergent geriatric syndrome), as well as physical and cognitive decline, with negative effect on dependance, nutrition and lifestyle, and eventually on responsiveness to and efficacy of treatments.

A frailty scale was recently described that categorized patients with MM as fit, intermediate or frail based on age, comorbidities, and physical and cognitive functioning. The frailty score was a predictor of death, progression of the disease, toxicity and drug discontinuation.

The aim of this study was to compare the first line standard treatments, the triplet VMP versus the doublet Rd, that were available when the study was designed. Until 17th December 2021, 228 patients were enrolled in this trial and randomized to VMP vs Rd. Since Dara-VMP and Dara-Rd have recently become the new standard regimens, in this amendment of the study, daratumumab is added to VMP and Rd.

In this project, we will compare available first line standard treatments, the triplet VMP versus the doublet Rd with or without daratumumab (Dara-VMP, Dara-Rd), in an unselected population of patients ≥ 65 years affected by MM in every day clinical practice.

In the last decade, many novel and expensive drugs have been approved for this disease, yet the general older population is not adequately represented in validating trials. Nevertheless, the results and treatments derived from those registrational trials have often been applied to the real-life older population, with a high risk to produce a negative impact on patient functional capacity and ability to carry out daily tasks, cognitive function, mental status, nutritional condition, social situation/capability to stay at home and finally affecting their quality of life (QoL) and OS.

The main aim of the project is to evaluate the best initial treatment for elderly MM patients and to compare benefits, risks, QoL and costs of currently available, standard treatments according to the patient frailty profile.

All patients will be randomized in a 1:1 ratio to receive:

ARM A (enrollment closed):

Bortezomib (V):

* 1.3 mg/m2 subcutaneously on days 1, 4, 8, 11, 22, 25, 29 and 32 in cycles 1-4;
* 1.3 mg/m2 subcutaneously on days 1, 8, 22 and 29 in cycles 5-9.

Melphalan (M):

- 9 mg/m2 orally on days 1, 2, 3 and 4 of each cycle.

Prednisone (P):

- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Each cycle is to be repeated every 42 days. Duration: Maximum 9 therapy cycles can be performed. After 9 cycles, patients will be observed until progression disease or the start of a new line of therapy.

ARM A2:

Bortezomib (V) 1. 3 mg/m2 subcutaneously twice weekly on weeks 1, 2, 4, and 5 of cycle 1 (days 1,4,8,11,22,25,29,32) and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9 (days 1,8,22,29) Melphalan (M):- 9 mg/m2 orally on days 1, 2, 3 and 4 of each cycle.

Prednisone (P):

- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Daratumumab (Dara) 16 mg per kilogram of body weight or 1800 mg Daratumumab subcutaneous (SC) (according to local clinical practice) with oral or intravenous dexamethasone (to manage infusion reactions) at a dose of 20 mg once weekly in cycle 1 (days 1,8,15,22,29,36), every 3 weeks in cycles 2 through 9 (days 1,22), and every 4 weeks thereafter until disease progression or unacceptable toxic effects. Dexamethasone at a dose of 20 mg was substituted for prednisone on day 1 of each cycle.

ARM B (enrollment closed):

Lenalidomide (R):

- 25 mg orally on days 1-21 of each cycle.

Dexamethasone (d):

- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycles. Duration: patients will receive treatment until any sign of progression or intolerance.

ARM B2

Lenalidomide (R):

- 25 mg orally on days 1-21 of each cycle.

Dexamethasone (d):

- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycles. Daratumumab (Dara) intravenous at a dose of 16 mg per kilogram of body weight or 1800 mg Daratumumab subcutaneous (SC) (according to local clinical practice) once weekly during cycles 1 and 2, every 2 weeks during cycles 3 through 6, and every 4 weeks thereafter; preinfusion medications were administered approximately 1 hour before each daratumumab dose.

STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA

A RANDOMIZED, MULTICENTER, OPEN LABEL STUDY COMPARING TWO STANDARD TREATMENTS, BORTEZOMIB-MELPHALAN-PREDNISONE (VMP) WITH OR WITHOUT DARATUMUMAB (Dara-VMP) VS LENALIDOMIDE-DEXAMETHASONE (Rd) WITH OR WITHOUT DARATUMUMAB (Dara-Rd) IN AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) INELIGIBLE COMMUNITY POPULATION AFFECTED BY MULTIPLE MYELOMA (MM)

Number of months from the date of randomization to the date of first observation of PD, or death from any cause as an event.

Overall response rate will include complete response (CR), very good partial response (VGPR) and partial response (PR) using the International Response Criteria. Responders are defined as subjects with at least a PR.

Time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the end of the study.

Time between randomization and death. Subjects who die will be censored at time of death as an event, regardless cause of death.

Time from randomization to objective tumor progression on next-line treatment or death from any cause.

Time to next therapy will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event.

Time to progression will be measured from the date of randomization to the date of first observation of PD, or deaths related to PD.

Safety will be evaluated by assessing the incidence, severity and type of AEs according to NCI-CTCAE v. 4.0.

Incidence of treatment discontinuation for toxicities as well as the rate of death for toxicity will be evaluated during the entire duration of the trial (toxicities evaluated according to NCI-CTCAE v. 4.0)

Validation of Myeloma Frailty Score (fit score=0; intermediate-fitness score=1, and frail score≥2) that assess comorbidities, cognitive and physical status in real population according to geriatric assessment and considering patients' non-Myeloma polydrug therapies.

Quality of Life will be evaluated through questionnaire: EORTC-QLQ-C30 (a generic, multidimensional, cancer-specific QoL questionnaire).

Quality of Life will be evaluated through questionnaire for MM patients: QLQ-MY20 (a specific 20- item MM module).

Quality of Life will be evaluated through questionnaire: EQ-5D-5L (a generic assessment of five health categories and overall health score).

Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating working activities.

Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating care assistance.

Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating health care visit.

Infectious risk complications will be evaluated through a scale evaluating the number of adverse events, severity, type of infection, need for hospitalization (yes/no), number of days of suspension of study treatment. All these data will be combined in the statistical analysis to combine different outcome of treatments.

University of Turin, Italy

Principal Investigator

Patients either continue DRd with daratumumab iv, switch to daratumumab sc or switch multiple times iv/sc

Patients either continue DRd with daratumumab sc, switch to daratumumab iv or switch multiple times sc/iv

Wolfgang Knauf, Prof. Dr.

MYLENE is a prospective, multicenter, NIS to evaluate the patient and HCP satisfaction of sc and iv application of daratumumab in routine clinical practice in Germany. Patients observed in this study will be transplant ineligible NDMM patients for which the physician foresees an anti-myeloma therapy using DRd regimen as per local label.

250 NDMM patients treated with DRd will be enrolled (excluding screening failures, i.e., enrolled patients not fulfilling selection criteria identified before treatment start will be replaced) within 12 months in a proportion of approximately 1/3 patients receiving daratumumab sc and 2/3 patients receiving daratumumab iv as per physician's decision.

Therapy options for MM are mainly dependent on the age and fitness of the patients. NDMM patients up to the age of 65-70 years in whom autologous stem cell transplantation is not indicated, anti-myeloma treatment traditionally consists of systemic chemotherapy, with adjunctive use of radiation or surgery in selected cases associated with extramedullary disease. However, the therapeutic landscape of multiple myeloma progressed in the past decade with the introduction of immunomodulatory agents, proteasome inhibitors and anti-CD38 antibodies, like Daratumumab.

After approval of daratumumab iv in May 2016, the sc daratumumab application route was approved in June 2020 in Germany. Real-world evidence data, however, are not yet available neither related to daily experience nor to satisfaction with daratumumab sc application nor to the proportion of patients potentially switching from daratumumab iv to sc application.

MYLENE aims to close these gaps with focus on NDMM patients who are ineligible for autologous stem cell transplantation and who will be treated with DRd; this is to guarantee a homogenous patient population.

All aspects of treatment and clinical management of patients will be in accordance with local clinical practice and applicable local regulations, and at the discretion of the healthcare provider (or treating physician where different). Only data available per clinical practice will be collected within this study. Additionally, where permitted in accordance with local regulations, healthcare providers will be asked to obtain patient-reported outcome (PRO) data from patients within this study. Despite use of PROs and HCP as well as physician questionnaires, the design is non-interventional due to the fact that the questionnaires are structured documentation aids to document questions that are routinely part of the dialog between patient and physician or HCP during the patient visit and/or drug administration or that are considered by the HCP when evaluate treatment for the patient but are not documented in the medical record.

MYLENE is unique as it is focusing on the satisfaction of all involved stakeholders (i.e., patients and HCPs) under real-word conditions and mainly in private practices, since this patient collective is treated preferentially in these institutions, allowing to receive direct feedback about the use of daratumumab sc application and its potential hurdles or/and limitations. Furthermore, this study will provide insights on how the sc/iv application is managed in clinical routine as well as how it is perceived by medical professionals over time.

This NIS will be analyzed exploratively and is hence not designed to confirm or refute a predefined hypothesis.

Non-interventional Study to Evaluate Patient and Healthcare Provider Satisfaction of Daratumumab Use in the Treatment of First-line Daratumumab, Lenalidomide, Dexamethasone (DRd) Multiple Myeloma Patients in Germany Depending on Application Route (sc or iv)

Prospective, Multicenter, Non-interventional Study to Evaluate Patient and Healthcare Provider Satisfaction of Daratumumab Use in the Treatment of First-line Daratumumab, Lenalidomide, Dexamethasone (DRd) Multiple Myeloma Patients as Per Routine Clinical Practice in Germany Depending on Application Route (sc or iv)

Occurence and number of patients with (treatment-related) adverse events will be provided.

Additionally, summary tables of selected subsets of AEs will be displayed summarized by system organ class (SOC) and preferred term (PT), sorted by frequency of SOC and PT. Summary tables for AEs will include only AEs that started or worsened during the on-treatment period. However, safety data from the pre- and post-treatment periods will be listed separately.

Time to first occurrence of AESI will be calculated for patient with an AESI as the time from the date of first application of daratumumab until onset of first documented AESI and will displayed with descriptive statistics.

The primary objective of this NIS is to exploratively analyze patients' satisfaction of sc and iv application of daratumumab over time as measured by the "Patient Satisfaction and Time Questionnaire" (PatSTQ).

Overall patients´ satisfaction with daratumumab administration will be displayed as the result of one defined question in the PatSTQ, with descriptive statistics and boxplots.

Results of PatSTQ will be displayed with frequencies per group and by time point. Additionally, stacked bar plots with questionnaire results (including missings) per item and time point will be presented

The secondary objective of this NIS is to assess HCPs' satisfaction of sc and iv application over time as measured by the "HCP Satisfaction and Time Questionnaire - patient specific" (HSTQ-ps).

HCPs' application route satisfaction will be displayed by questionnaire time point as result of the HSTQ - ps questionnaire with frequencies for questions and with descriptive statistics.

The proportion of HCP active time spent on activities (drug preparation, drug administration, patient care/patient monitoring) over time

Patients' overall time spent at doctor's office

The switch rate (proportion of patients) of daratumumab application routes during 12 months of study participation under real-word conditions

The main reasons for sc or iv application selection evaluated by both, the "Physician Therapy Decision Questionnaire - general" (PTDQ-g) at study start and at the end of study (i.e., study close-out) and by the "Physician Therapy Decision Questionnaire - patient specific" (PTDQ-ps) at baseline and at switch of the application route

The impact of different factors on therapy decision and application route selection will be displayed as parameter estimates for selected fixed covariates (age, cytogenetics (high vs standard) and relevant comorbidities) in a mixed effects logistic regression model with the result of PTDQ-ps as outcome.

The treating physician selects up to two main reasons why the (new) application route (sc or iv) of daratumumab for a patient is chosen.

Patients' preference of the application route (only for patients switching from one application route to another) as measured by the "Patient Preference Questionnaire" (PatPQ).

The patient selects which method of daratumumab administration (iv or sc) is preferred and up to two reasons for the preference.

iOMEDICO AG

Anti-Infective Agents

Thalidomide

Anti-Bacterial Agents

Carfilzomib + Thalidomide + Dexamethasone (KTd) for 9 cycles (day 1-28) Followed by second randomisation: maintenance arm with carfilzomib monotherapy versus "observation only" arm

Carfilzomib + Lenalidomide + Dexamethasone (KRd) for 9 cycles (day 1-28) Followed by second randomisation: maintenance arm with carfilzomib monotherapy versus "observation only" arm

Induction treatment: Cycle 1 day 1+2: 20 mg/m2; days 8,9, 15 and 16: 27 mg/m2; Cycle 2: 27 mg/m2 on days 1,2,8,9,15 and 16; Cycle 3-9: 56 mg/m2 on days 1, 8 and 15; IV duration: 30-60 minutes; Maintenance treatment with carfilzomib (last tolerated dose on day 1 and 15 (± 7 days) of each cycle)

Carfilzomib

100mg orally on days 1-28 in patients \<75 years of age at Cycle 1; 50mg p.o. on days 1-28 in patients ≥ 75 years of age at Cycle 1

40mg p.o. on days 1, 8, 15,22 (± 1 day ) in patients \<75 years of age at Cycle 1; 20mg p.o. on days 1, 8, 15, 22 (± 1 day) in patients ≥ 75 years of age at Cycle 1, given 4 hours-30 min prior to carfilzomib

Heinz Ludwig, MD

This is a randomized, 2-arm phase II, multi-center study to evaluate the overall response rate in newly diagnosed, transplant ineligible patients receiving 9 cycles induction therapy with either KTd or KRd followed by randomization to either carfilzomib maintenance treatment for 12 months or to observation only. Maintenance is given for 12 cycles or progression of disease, whatever occurs first.

Multiple myeloma, a clonal neoplastic proliferation of plasma cells, is the second most common hematologic malignancy and accounts for approximately 72,000 annual deaths worldwide. There are an estimated 11,000 deaths per year in the US and more than 19,000 deaths per year in Europe.

This study examines the efficacy of carfilzomib (K) in combination with thalidomide, an old, well established first line immunomodulatory imide drugs (IMiD) in newly diagnosed multiple myeloma versus K in combination with lenalidomide in 1st line. This trial will also evaluate the adherence to and the safety of a thalidomide containing triplet by using a non-neurotoxic proteasome inhibitor. Moreover, weekly dosing of carfilzomib addresses the need for a more convenient dosing schedule. Finally, yet importantly, this trial will assess the efficacy of a less cost intensive triplet and a strategy to keep lenalidomide as backup for later lines.. The second part of the study - after completing 9 cycles induction therapy with KTd or KRd - patients of both arms will be pooled and again randomized 1:1 stratified by induction therapy into two arms (K-monotherapy versus observation-only).

Patients With Newly Diagnosed Multiple Myeloma Comparing KTd vs. KRd Induction Therapy and Investigating a K-mono Maintenance Strategy

A Randomized Phase II, 2-armed Study in Transplant Ineligible (TI) Patients With Newly Diagnosed Multiple Myeloma (NDMM) Comparing Carfilzomib + Thalidomide + Dexamethasone (KTd) Versus Carfilzomib + Lenalidomide + Dexamethasone (KRd) Induction Therapy With Respect to Response Rates and Investigating a Carfilzomib (K) Monotherapy Maintenance Strategy

Overall response rate (ORR) will be assessed according to International Myeloma Working Group (IMWG) criteria to determine the ORR in patients NDMM after receiving 9 cycles induction therapy with either carfilzomib in combination with thalidomide and dexamethasone or carfilzomib in combination with lenalidomide and dexamethasone

Feasibility of maintenance therapy with carfilzomib will be investigated in comparison with observation only strategy by observing treatment and visit compliance (listing withdrawals, treatment/visit delays and drug modifications).

Safety will be assessed by the type, incidence, severity (CTCAE v 4.0), and relatedness of adverse events (AEs) to treatment and by the descriptive analysis of laboratory parameters related to safety. Adverse events will be summarized by presenting the number and percentage (as appropriate) of patients having any adverse event by body system, type of adverse event, and maximum severity.

After 12 months maintenance treatment or observation overall response rate (ORR, ratio of the number of patients with CR to partial response (PR) divided by the number of all patients evaluable for response) will be analyzed descriptively and compared using a chi\^2 test without continuity correction. A one-sided 97.5% confidence interval for the difference in ORR will be calculated.

The updated IMWG response criteria will be applied for response evaluation in all patients; this also includes minimal residual disease (MRD) evaluation; thus, response rates will be assessed qualitatively and quantitatively; MRD testing will be performed in all patients achieving complete remission (CR) and in patients which are in a CR at the end of maintenance

To determine Overall Survival (OS) in patients with NDMM ineligible for transplantation receiving either KTd versus KRd induction therapy and sub-sequent being randomised either to maintenance arm with carfilzomib or to control only for a maximum period of 12 months.

Response rates will be assessed qualitatively and quantitatively (PR, VGPR, CR, sCR, MRD according to IMWG Rajkumar 2011)

Safety and tolerability of KTd and KRd followed by randomization to carfilzomib maintenance for a maximum period of 12 months or observation only will be assessed by the type, incidence, severity (CTCAE v 4.0), and relatedness of AEs to treatment and by the descriptive analysis of laboratory parameters related to safety. Adverse events will be summarized by presenting the number and percentage (as appropriate) of patients having any adverse event by body system, type of adverse event, and maximum severity.

Changes in quality of life will be analyzed by using the cancer patient-specific questionnaire EORTC-QLQ-C30. Measures will be calculated and analyzed descriptively, and compared between treatment groups using a Mann-Whitney U-test for unpaired observations.

Changes in quality of life will be analyzed by using the multiple myeloma-specific questionnaire "EORTC-QLQ-MY20". Measures will be calculated and analyzed descriptively, and compared between treatment groups using a Mann-Whitney U-test for unpaired observations.

Changes in general health status will be analyzed by using the questionnaires "EQ-5D-5L". QoL measures will be calculated and analyzed descriptively, and compared between treatment groups using a Mann-Whitney U-test for unpaired observations.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.	NCT05527340	Multiple Myelom...	Iberdomide Dexamethasone Daratumumab	18 Years -	PETHEMA Foundation
A Trial to Evaluate the Efficacy and Safety of Tafasitamab With Bendamustine (BEN) Versus Rituximab (RTX) With BEN in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)	NCT02763319	Diffuse Large B...	Rituximab (RTX) Tafasitamab Bendamustine (B...	18 Years -	MorphoSys AG
STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA	NCT03829371	Multiple Myelom...	Velcade Melphalan Prednisone Lenalidomide Dexamethasone Daratumumab	65 Years -	University of Turin, Italy
STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA	NCT03829371	Multiple Myelom...	Velcade Melphalan Prednisone Lenalidomide Dexamethasone Daratumumab	65 Years -	University of Turin, Italy
Non-interventional Study to Evaluate Patient and Healthcare Provider Satisfaction of Daratumumab Use in the Treatment of First-line Daratumumab, Lenalidomide, Dexamethasone (DRd) Multiple Myeloma Patients in Germany Depending on Application Route (sc or iv)	NCT05284591	Multiple Myelom... Newly Diagnosed Transplant Inel... Patient Satisfa... Patient Prefere... Personal Satisf...	Daratumumab	18 Years -	iOMEDICO AG
Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.	NCT05527340	Multiple Myelom...	Iberdomide Dexamethasone Daratumumab	18 Years -	PETHEMA Foundation
Patients With Newly Diagnosed Multiple Myeloma Comparing KTd vs. KRd Induction Therapy and Investigating a K-mono Maintenance Strategy	NCT02891811	Multiple Myelom...	Carfilzomib Thalidomide Lenalidomide Dexamethasone	18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie

Spots Global Cancer Trial Database for transplant ineligible