Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Disease Progression

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Bevacizumab

Albumin-Bound Paclitaxel

Belinostat

Histone Deacetylase Inhibitors

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Enzyme Inhibitors

This is a one arm, open label study of the investigational medication Belinostat.

Induction therapy will include 6 cycles of 5-days of medication administration followed by a 16 day rest period. Belinostat will be given once a day for 5 days total. Three dose levels will be evaluated (600mg/kg, 800 mg/kg, and 1000 mg/kg). In addition, participants will receive fixed doses of intravenous carboplatin (AUC 6), Paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) once on day 3 of each cycle. Serial disease status evaluations will be done throughout the study.

In the absence of significant toxicity or disease progression, participants may continue with a maintenance regimen of bevacizumab and Belinostat for an additional 6 cycles. The dose of Belinostat received during maintenance will be that tolerated in the initial 6 cycles.

Belinostat, carboplatin, paclitaxel and bevacizumab

Martin E Guiterrez, MD

The purpose of this study is to establish the safest dose of the investigational medication Belinostat that can be administered with a standard of care chemotherapy regimen of bevacizumab, carboplatin, and paclitaxel. Further study will examine the short and long-term effect (up to 2 years) of this medication on participant's disease status and overall survival.

This is a Phase Ib/II, single center, open label, dose-finding study to evaluate the use of Belinostat when given with standard of care chemotherapy in patients with untreated, non-small cell lung cancer (NSCLC). In the Phase Ib portion, dose limiting toxicity evaluation will be used to determine the maximum tolerated dose (MTD) of Belinostat when given with fixed doses of bevacizumab, carboplatin, and paclitaxel(a BelCap-B regimen). Three dose levels of Belinostat are proposed (600mg/kg, 800mg/kg, 1000mg/kg). Determination of MTD will be the basis for establishing set dosing for the phase II component of the study.

The phase II portion of the study includes further drug safety evaluation and a preliminary assessment of efficacy of Belinostat when used with specified induction and maintenance regimens. Response will be evaluated through the RECIST criteria. Additional analysis will be done to estimate the time to response, progression free survival, median survival, and overall survival (OS) in study participants to 2 years post-initiation of cycle 1.

Based on a standard 3 x 3 statistical design, the phase Ib portion may accrue between 3 to 12 participants. Phase II will have a minimum sample size of 10 and a maximum of 16 patients. Participants who complete the Phase I portion and are able to advance to Phase II, will be evaluable for the Phase II objectives.

Safety and Efficacy of Belinostat When Used With Standard of Care Chemotherapy for Untreated Non-small Cell Lung Cancer

Phase Ib/II Study to Determine the Recommended Dose, Safety, and Preliminary Efficacy of Belinostat When Used in Combination With Carboplatin, Paclitaxel, and Bevacizumab in Patients With Untreated Non-small Cell Lung Cancer.

The aim of the initial phase Ib component is to establish the maximum tolerated dose (MTD) of Belinostat when used with a standard of care carboplatin, paclitaxel and bevacizumab course of therapy ("BelCap-B") regimen. The MTD will be determined through the process of dose-limiting-toxicity evaluation.

The percentage of participants who are alive at 2 years post initiation of investigational treatment.

Long-term (up to 2 years) safety evaluation of the investigational treatment will be evaluated by ongoing evaluation of adverse events/late-effects using the NCI Common Toxicity Criteria.

Response to therapy will be measured by the RECIST criteria. The investigators will assess the percentage of research participants whose disease status indicates a response to investigational treatment according to the RECIST criteria.

The number (%) of participants who do not show evidence of disease progression (according to RECIST criteria)at 2 years post initial administration of the investigational product.

Holy Cross Hospital, Florida

Executive Director of Clinical Research

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Leukemia

Graft vs Host Disease

Neoplasms by Histologic Type

Hematologic Diseases

Homologous Wasting Disease

Fludarabine

Fludarabine phosphate

Thymoglobulin

Busulfan

Antilymphocyte Serum

Immunosuppressive Agents

Immunologic Factors

Alkylating Agents

Antineoplastic Agents, Alkylating

All patients on this trial will receive a conditioning regimen of Busulfan, Fludarabine, Anti-Thymocyte Globulin and Total Body Irradiation (400 cGy)

Patient will receive a Test Dose of Busulfan on either Day -10 or Day -9. Patient will receive their Regimen Dose of Busulfan on Day -5 to Day -2. The regimen dose of Busulfan will be based off of the findings from their Test Dose.

Patient will receive Fludarabine from Day -6 to Day -2. The dose of Fludarabine will be 30 mg/m\^2/day.

The patient will also receive Thymoglobulin (rabbitATG) on Day -4 to Day -2. Each dose of rabbitATG will be 1.5 mg/kg/day.

On Day -1 the patient will receive a total of 400 cGy of Total Body Irradiation.

Total Body Irradiation

Sonali Chaudhury, MD

Colleen E Rosen, BS, RN

The study proposes the use of Fludarabine, Busulfan, Anti Thymocyte Globulin Rabbit (ATG) and Total Body Irradiation as a preparative regimen before hematopoietic stem cell transplant from unrelated donor peripheral blood stem cells (PBSC). The hypothesis states that the 100 day mortality after this type of transplant will be significantly below the accepted standards, which is about 30% for unrelated donors.

The primary objective of this study is to evaluate the toxicity (as measured as 100 day survival) after hematopoietic stem cell transplant from an unrelated donor with a novel preparative regimen of Fludarabine, Busulfan, Anti-Thymocyte Globulin, and Total Body Irradiation for pediatric patients with leukemia. The secondary objectives are to evaluate the relapse-free and overall survival after hematopoietic stem cell transplant as well as to evaluate the incidence of acute and chronic graft-versus-host disease after this preparative regimen.

Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors

Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors Using Fludarabine, Busulfan, 400 cGy Total Body Irradiation, and Thymoglobulin

Ann & Robert H Lurie Children's Hospital of Chicago

Recurrence

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Mantle Cell Lymphoma

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Bendamustine 90 mg/m² d 1+2 + Rituximab 375 mg/m² d 1 q4w

Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w

Bendamustine 90 mg/m² d 1+2 + Rituximab 375 mg/m² d 1 q4w for maximum 6 cycles

Bendamustine plus Rituximab

Fludarabine 25 mg/m² d 1-3 + Rituximab 375 mg/m² d 1 q4w for maximum 6 cycles

The study addresses the question if a therapy with bendamustine plus rituximab is comparable (non inferior) with the well-tried combination of fludarabine plus rituximab with regard to event free survival (EFS) in recurrent low malignant Non-Hodgkin and mantle cell lymphomas.

Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab

Prospective Randomised Multicenter Study for Therapy Optimization of Recurrent, Progressive Low Grade Non-Hodgkin Lymphomas and Mantle Cell Lymphomas

From date of randomization until the date of first documented progression, date of detection of a secondary malignancy or date of death from any cause, whichever came first. Minimum 1 year

University of Giessen

Professor Mathias Rummel

Lymphoma, Follicular

Follicular Lymphoma

Anti-Infective Agents

Etoposide

Cytarabine

Melphalan

Etoposide phosphate

Antimetabolites

Antiviral Agents

High Dose Chemotherapy (HDT) containing :

* Bendamustine
* Etoposide
* Cytarabine
* Melphalan

HDT will be followed by an Autologous Stem Cell Transplantation

High Dose Chemotherapy (HDT) containing :

* Bendamustine 160 mg/m2 for 2 days (D-8 and D-7)
* Etoposide 200 mg/m2 and Cytarabine 400 mg/m2 for 4 days (D-6 to D-3)
* Melphalan 140 mg/m2 on D-2

HDT will be followed by an Autologous Stem Cell Transplantation on D0

BeEAM

Hervé Ghesquières, Dr

The purpose of this study is to evaluate the efficacy and safety of BeEAM (bendamustine, etoposide, cytarabine and melphalan) regimen prior to autologous stem cell transplant for first and second chemosensitive relapses in patients with follicular lymphoma (World Health Organisation (WHO) grade 1, 2, 3a).

The natural history of this follicular lymphoma (FL) is marked by multiple relapses. The prognosis of FL has improved with the use of effective sequential chemotherapy and the introduction of anti-cluster of differentiation antigen 20 (anti-CD20) monoclonal antibody. Based on the multiple phases II, high dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) appear to be an effective treatment in relapsed FL. At rituximab era, the 3-years EFS rate was 75% for relapsed transplanted patients treated in first line therapy in FL2000 protocol. Bendamustine that combines alkylating and antimetabolite activities had proven clinical activity in relapse and in first line therapy of FL. Carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM regimen) is one of the most used schedule of HDT in non hodgkin lymphoma. Regarding the good safety profile of Bendamustine, Visani et al. proposed a phase I/II of bendamustine at day -7 and -6, followed by etoposide, cytarabine and melphalan with similar dose than BEAM regimen. The bendamustine maximal dose is 200 mg/m² day -7, -6. Data from engraftment showed closed results than those observed after BEAM. None of patients experienced a dose limiting toxicity. In this context, the investigators proposed to perform a multicentric phase II of this regimen with 200 mg/m² day-7 and -6 of bendamustine for first and second relapsed FL with a chemosensitive disease after salvage therapy. No FL was evaluated in Visani et al. study. In addition, the investigators can observe a shortage of the BCNU these last years that incline to evaluate new schedule of HDT.

BENdamustine at Elevated Dose for Relapsed Follicular Lymphoma in Intensification Therapy and Transplantation (BENEFIT)

A Multicenter Phase II Study Evaluating BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Prior to Autologous Stem Cell Transplant for First and Second Chemosensitive Relapses in Patients With Follicular Lymphoma

EFS will be measured from the date of inclusion to the date of event defined as : death due to any cause, relapse/progression, or changes in therapies. Patients with no event at the time of analysis will be censored at the date of the last contact

The safety analyzable population include all patients who received at least one dose of BeEAM regimen

ORR is defined by the rate of patients in Complete Response (CR) and in Partial Response (PR) at time of evaluation.

ORR is assessed according to Cheson et al. 2007 criteria

ORR is defined by the rate of patients in Complete Response (CR) and in Partial Response (PR) at time of evaluation.

ORR assessed according to Cheson et al. 1999 criteria

PFS will be measured from the date of inclusion to the date of event defined as : progression/relapse or death due to any cause. Patients with no event at the time of analysis will be censored at the date of the last contact.

PFS will be assessed among all included patients and in the subgroup of complete responders at the beginning of HDT.

OS will be measured from the date of inclusion to the date of death due to any cause and will be censored at the date of last contact for the patients alive at last contact

Centre Leon Berard

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Bortezomib

Bortezomib consolidation : 20 injections starting 3 months after ASCT

Bortezomib 1,3 mg/sqm Days 1,4,8,11 for two 3-week cycles and then once a week for three weeks in 4 4-week cycles

bortezomib

Ulf-Henrik Mellqvist, Dr., PhD

Multiple myeloma is a malignant incurable hematological disease where survival has been significantly improved by high-dose melphalan with autologous stem cell support (ASCT) in younger patients. However, the disease will eventually relapse and new treatment is demanded. Bortezomib is a newly approved drug for treating relapsing multiple myeloma. It has a different biological effect and response even in patients refractory to conventional chemotherapy. The purpose of the study is in a randomized design to investigate if addition of bortezomib by 20 injections during a 4 months period starting 3 month after ASCT can prolong the time to progression compared to patients receiving no consolidation or maintenance therapy.

Rationale:

ASCT prolongs EFS and OS for myeloma patients \< 65 years of age. During the period from ASCT to progression most myeloma patients experience few symptoms and have a good quality of life11. A further prolongation of EFS would be a big step forward in myeloma treatment. Bortezomib is a new promising agent, which has shown clear anti-myeloma effect in heavily pre-treated patients. After ASCT the tumour cell burden is low and it is the hypothesis of this clinical trial that the unique mechanism of action of bortezomib may reduce the number of tumour cells even further and by doing so prolong EFS.

Primary objective:

\* Evaluate the effect on EFS (an event is defined as either progression or death of any cause without preceding progression) of consolidation treatment with bortezomib after ASCT compared to no consolidation

Secondary objectives:

* Overall survival from ASCT
* Overall survival from start of relapse treatment
* Time to need for relapse treatment
* Response rate in patients not in CR following ASCT
* Toxicity from consolidation treatment
* Quality of life
* Cost utility
* Planned subgroup analysis: comparison of primary and secondary endpoint in patients receiving one vs. two high dose treatments

Efficacy of Bortezomib Consolidation After High-dose Melphalan With Stem Cell Support in Myeloma Patients

Clinical Protocol Bortezomib Consolidation in Patients With Myeloma Following Treatment With High-dose Melphalan and Autologous Stem Cell Support. A Randomised NMSG Trial (15/05)

Janssen-Cilag Ltd.

Nordic Myeloma Study Group

Ulf-Henrik Melqvist

Hematopoietic Stem Cell Transplantation

Benedetto Bruno, MD, PhD

Mario Boccadoro

Bruno Benedetto, MD, PhD

To evaluate toxicity profile and efficacy of a tandem autologous-nonmyeloablative transplant approach in newly diagnose myeloma patients younger than 65 years

Tandem Autologous- Nonmyeloablative Allogeneic Transplant for Newly Diagnosed Multiple Myeloma (Trapianto Tandem Autologo-Allogenico Non Mieloablativo Nel Mieloma Alla Diagnosi)

Allogeneic Stem Cell Transplantation for Multiple Myeloma: a Two Step Approach to Reduce Toxicity Involving High-Dose Melphalan and Autologous Stem Cell Transplant Followed by PBSC Allografting After Low-Dose TBI

Azienda Ospedaliera San Giovanni Battista

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasm, Residual

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Daunorubicin

Idarubicin

Midostaurin

Protein Kinase Inhibitors

Participants received Midostaurin in Induction 50mg twice daily on Day 8 until 48 hrs before start of next cycle. During Induction 2 and consolidation 50mg twice daily on Day 4 until 48 hrs before start of next cycle. During post-consolidation 50mg twice daily for 28 consecutive days of each 28-day treatment cycle up to 12 cycles. For participants who could not tolerate the protocol-specified dosing schedule, dose interruptions and/or reductions were either recommended or mandated allowing participants to continue the study treatment. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation.

Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation

Midostaurin was provided as 25 mg capsules 8PC, was supplied as double-blind in blister packs and taken orally.

Placebo was provided as 25 mg soft gelatin capsules 8PC, was supplied as double-blind in blister packs and taken orally.

Placebo

Along with the study drug/placebo, chemotherapy was given as well: either Daunorubicin or Idarubicin and Cytarabine - all taken by i.v.

Chemotherapy

Novartis Pharmaceuticals

The purpose of this study was to confirm the preliminary evidence from early clinical trials that midostaurin may provide clinical benefit not only to AML patients with the FLT3-mutations but also in FLT3-MN (SR\<0.05) AML (FLT3 mutant to wild type signal ratio below the 0.05 clinical cut-off).

This study evaluated the efficacy and safety of midostaurin in combination with daunorubicin or idarubicin and cytarabine for induction and intermediate-dose cytarabine for consolidation, and midostaurin single agent post-consolidation therapy in newly diagnosed patients with FLT3-MN (SR\<0.05) AML.

This was a multi-center, multinational, randomized, double-blind Phase III study using a group sequential design. Subjects were stratified according to age (\<60 vs. ≥ 60 years). Subjects within each stratum were randomized in a 1:1 ratio into one of two treatment arms: Midostaurin + chemotherapy 'or' Placebo + chemotherapy.

The study consisted of the following phases:

Screening/randomization phase: Subjects had to sign informed consent form before screening for enrollment. Subjects started chemotherapy at day 1 and were randomized at day 8.

Induction phase: All subjects received at least one cycle (28 days) of induction therapy with continuous infusion cytarabine (D1 - D7) and daunorubicin or idarubicin (D1 - D3) (induction 1). Subjects who did not achieve CR or CRi with adequate blood count recovery after Induction 1 received a second cycle with intermediate-dose cytarabine (D1 - D3) and daunorubicin or idarubicin (D1 - D3) (induction 2). Subjects who did not achieve CR or CRi with adequate blood recovery after induction 2 discontinued study treatment and were followed for survival.

Consolidation phase: Subjects who achieved CR or CRi with adequate blood count recovery after induction with one or two cycles of induction proceeded to consolidation therapy with either 3 or 4 cycles respectively of intermediate-dose cytarabine (D1 - D3), or to Hematopoietic Stem Cells Transplantation (HSCT) with or without preceding consolidation cycles.

Post-consolidation phase: Subjects who maintained CR or CRi with adequate blood count recovery at the end of the consolidation phase received 12 cycles (28 days/cycle) of continuous therapy with midostaurin or placebo twice daily at 50 mg. Subjects who underwent HSCT after achieving CR or CRi with adequate blood count recovery received midostaurin or placebo twice daily 50 mg post-transplant therapy, continuously, for up to 12 cycles (28 days/cycle). Post HSCT post-consolidation therapy began \>30 days but not later than 100 days following HSCT.

Follow-up phase: All enrolled subjects were followed through the treatment period and until relapse/treatment failure, thereafter for start of new line of therapy and survival.

A Global Study of the Efficacy and Safety of Midostaurin + Chemotherapy in Newly Diagnosed Patients With FLT3 Mutation Negative (FLT3-MN) Acute Myeloid Leukemia (AML)

A Phase III, Randomized, Double-blind Study of Chemotherapy With Daunorubicin or Idarubicin and Cytarabine for Induction and Intermediate Dose Cytarabine for Consolidation Plus Midostaurin (PKC412) or Chemotherapy Plus Placebo in Newly Diagnosed Patients With FLT-3 Mutation Negative Acute Myeloid Leukemia (AML)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

EFS was defined as the time from randomization to failure to obtain a complete remission (CR) or Complete remission with incomplete hematologic recovery (CRi) with adequate blood count recovery in induction, relapse after CR or CRi with adequate blood count recovery or death due to any cause, whichever occurred first as assessed by the investigator.

OS was defined as the time from randomization to date of death due to any cause. Patients entered the survival follow-up phase once they completed the safety follow up period (30 days after the last dose of midostaurin/placebo) in case of induction failure or if they had relapsed during post-treatment follow-up. Patients were then contacted by telephone every 3 months +/- 2 weeks or had a visit to follow up on their survival status, per Kaplan-Meier estimates.

Assessment was based on the International Working Group (IWG) criteria for AML as per investigator assessment.

CR: Bone marrow: \< 5% blasts no blasts with Auer rods; Peripheral blood: neutrophils ≥ 1.0 x 109/L platelets ≥ 100 x 109/L, no blasts; No evidence of extramedullary disease (such as central nervous system (CNS) or soft tissue involvement); Transfusion independent.

CRi with adequate blood count recovery is defined as the following:

Bone marrow \< 5% blasts no blasts with Auer rods Peripheral blood Neutrophils \>= 1.0 x 109/L and 50 x 109/L \<=platelets \< 100 x 109/L no blasts No evidence of extramedullary disease (such as CNS or soft tissue involvement).

MRD- rate was defined as the rate of participants reaching MRD at any timepoint. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP).

MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment.

MRD- rate was defined as the rate of participants reaching MRD at any timepoint during Post-consolidation phase. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP).

MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment.

Time to MRD- is defined as time from randomization to first occurrence of MRD-. Participants with leukemic blasts below 0.1% were considered as MRD-negative based on leukemia-associated immunophenotype (LAIP).

MRD was derived from bone marrow and blood data using cellular and molecular technologies and MRD status was measured using the flow cytometry assessments for LAIP irrespective of the investigator's overall clinical response assessment.

DFS as measured from the date of first CR or CRi with adequate blood count recovery to relapse or death due to any cause, whichever occurred first. Participants who did not relapse nor die were censored at the last adequate response assessment. Assessment was based on the IWG criteria for AML as per investigator assessment

Cumulative Incidence of Relapse (CIR) was defined for participants with CR or CRi with adequate blood count recovery and was the time from achieving the CR or CRi with adequate blood count recovery until the onset of relapse from CR or CRi with adequate blood recovery. Participants without relapse were censored at the last adequate response assessment. Participants who died without relapse were counted as a competing cause of failure.

Cumulative Incidence of Death (CID) was defined for all participants achieving CR or CRi with adequate blood count recovery measured from the date of achievement of CR or CRi until the date of death due to any reason. Participants not known to have died were censored on the last contact date. Participants who experienced relapse were counted as a competing cause of failure.

Time to CR or CRi with adequate blood count recovery was defined as the time from randomization to CR or CRi with adequate blood count recovery whichever occurred first

The time to neutrophil recovery was assessed for the following criteria: Partial neutrophil recovery: Number of days from start of treatment to the first day neutrophils ≥0.5 x 10\^9/L.

Full neutrophil recovery: Number of days from start of treatment to the first day neutrophils ≥1.0 x 10\^9/L

Time to platelet recovery was assessed for the following criteria: Partial platelet recovery: Number of days from start of treatment to the first day platelets ≥50 x 10\^9/L.

Full platelet recovery: Number of days from start of treatment to the first day platelets ≥100 x 10\^9/L.

Serial pharmacokinetics (PK) samples were collected in Non-poor metabolizer participants to assess the plasma concentrations of midostaurin, CGP52421 and CGP62221.

The AUC from time zero to a measurable concentration sampling time (t) (mass x time x volume-1). Note: as the last sampling time was at 12 h, AUC0-12h was determined after the first dose, reported at Cycle 1, Day 8

The AUC from time zero to the last measurable concentration sampling time after the first dose reported at Cycle 1, Day 8

The maximum (peak) observed plasma drug concentration after the first dose administration reported at Cycle 1, Day 8

The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration reported at Cycle 1, Day 8

The total FACT-Leu score consists of 44 items with total scores ranging from 0 to 176. Higher scores indicate better health-related quality of life ( HRQoL). Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL.

The EQ5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The patient is asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. The questionnaire also included a Visual Analogue Scale (VAS), where the patient is asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state.

Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post-treatment survival follow-up are not considered Adverse Events. The total number at risk in the post-treatment survival includes patients that entered the post-treatment survival follow-up period.

AEs during on-treatment period (up to 30 days post-treatment)

Midostaurin + Chemotherapy (On-treatment)

Placebo + Chemotherapy (On-treatment)

Deaths collected in the post- treatment survival follow-up phase (starting from day 31 post- treatment). No AEs were collected during this period

Midostaurin + Chemotherapy (Post-treatment Survival Follow-up)

Placebo + Chemotherapy (Post-treatment Survival Follow-up)

Midostaurin + Chemotherapy

Participants received matching placebo to midostaurin with same dose, plus chemotherapy. Chemotherapy consisted of daunorubicin or idarubicin and cytarabine for induction and intermediate dose cytarabine for consolidation.

Placebo + Chemotherapy

Full analysis set (FAS) comprised all participants to whom study drug was assigned by randomization.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficacy of Belinostat When Used With Standard of Care Chemotherapy for Untreated Non-small Cell Lung Cancer	NCT01090830	Non-Small-Cell ...	Belinostat, car...	18 Years -	Holy Cross Hospital, Florida
Safety and Efficacy of Belinostat When Used With Standard of Care Chemotherapy for Untreated Non-small Cell Lung Cancer	NCT01090830	Non-Small-Cell ...	Belinostat, car...	18 Years -	Holy Cross Hospital, Florida
Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors	NCT00679536	Leukemia	Busulfan Fludarabine Thymoglobulin Total Body Irra...	- 21 Years	Ann & Robert H Lurie Children's Hospital of Chicago
Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab	NCT01456351	Non-Hodgkin's L... Mantle Cell Lym...	Bendamustine pl... Fludarabine 25 ...	18 Years -	University of Giessen
Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors	NCT00679536	Leukemia	Busulfan Fludarabine Thymoglobulin Total Body Irra...	- 21 Years	Ann & Robert H Lurie Children's Hospital of Chicago
BENdamustine at Elevated Dose for Relapsed Follicular Lymphoma in Intensification Therapy and Transplantation (BENEFIT)	NCT02008006	Follicular Lymp...	BeEAM	18 Years - 65 Years	Centre Leon Berard
Efficacy of Bortezomib Consolidation After High-dose Melphalan With Stem Cell Support in Myeloma Patients	NCT00417911	Multiple Myelom...	bortezomib	18 Years -	Nordic Myeloma Study Group
BENdamustine at Elevated Dose for Relapsed Follicular Lymphoma in Intensification Therapy and Transplantation (BENEFIT)	NCT02008006	Follicular Lymp...	BeEAM	18 Years - 65 Years	Centre Leon Berard
Tandem Autologous- Nonmyeloablative Allogeneic Transplant for Newly Diagnosed Multiple Myeloma (Trapianto Tandem Autologo-Allogenico Non Mieloablativo Nel Mieloma Alla Diagnosi)	NCT00702247	Multiple Myelom...	Hematopoietic S...	18 Years - 65 Years	Azienda Ospedaliera San Giovanni Battista
A Global Study of the Efficacy and Safety of Midostaurin + Chemotherapy in Newly Diagnosed Patients With FLT3 Mutation Negative (FLT3-MN) Acute Myeloid Leukemia (AML)	NCT03512197	Acute Myeloid L...	Midostaurin Placebo Chemotherapy	18 Years -	Novartis

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