Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Heart and Blood Diseases

Rare Diseases

Syndrome

Myeloproliferative Disorders

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Diseases

Hematologic Diseases

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

* DNA extraction from blood sample for CALR mutation quantification (fragment analysis)
* at diagnosis and follow-up (inclusion period: 3 years)
* max 1 sample/year
* secondary outcome: mutational landscape by Next Generation Sequencing (NGS) analysis at diagnosis

CALR allele burden quantification

Laurane COTTIN, Doctor

Emma BLANCHET

Laurane COTTIN, Dr

Prospective study to evaluate the relevance of CALR allele burden monitoring as a molecular marker of disease progression.

A first local study on 45 patients showed the prognostic impact of CALR mutation quantification in follow-up, independently of the European LeukemiaNet (ELN) prognostic score validated in this group of patients.

This study aims to evaluate a multicenter cohort of 260 patients, including all types of CALR-mutated MPNs and several follow-up samples, to model the temporal evolution of CALR allele burden.

Blood of MPN patients will be collected, at the time of diagnosis and for 3 years (max 1 sample/year), for the quantification of the CALR allele burden. During follow-up, a clinicobiological score to define the progression or not of the disease for each patient will be evaluated in Essential Thrombocythemia (ET) and MyeloFibrosis (MF).

Interest of CALR Allele Burden in Diagnosis and Follow-up of Patients With CALR Mutated Myeloproliferative Syndromes (CALRSUIVI)

Clinicobiological score :

For ET, disease progression if ≥ 1 of:

* leukocytosis \> 12 G/L or myelemia \> 10% or erythroblasts \> 1%,
* anemia or thrombocytopenia not related to drug toxicity,
* development or worsening of splenomegaly,
* development of thrombocytosis (platelets \> 450 G/L) on cytoreductive therapy,
* poor disease control (at least one change in therapy for reasons other than adverse events),
* hematologic transformation or death related to hematologic pathology.

For MF, disease progression if ≥ 1 of:

* anemia \< 100 g/L, neutropenia \< 1 G/L, thrombocytopenia \< 100 G/L and/or development of general signs not previously present or recurring after improvement,
* increase in leukocytosis \> 25 G/L not previously present,
* appearance or aggravation of transfusion dependence,
* appearance (\> 5 cm) or aggravation (\> 50%) of splenomegaly,
* leukemic transformation or death related to the hematologic pathology.

Ligue contre le cancer, France

University Hospital, Angers

Neoplasms

Polycythemia Vera

Polycythemia

Bone Marrow Neoplasms

Hematologic Neoplasms

All Drugs and Chemicals

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants with polycythemia vera will receive 100 mg of momelotinib.

Participants with polycythemia vera will receive 200 mg of momelotinib.

Participants with essential thrombocythemia will receive 100 mg of momelotinib.

Participants with essential thrombocythemia will receive 200 mg of momelotinib.

Momelotinib tablet administered orally once daily

Momelotinib

Peter Lee, MD, PhD

This open-label study is to determine the safety and efficacy of momelotinib in participants with either polycythemia vera (PV) or essential thrombocythemia (ET) who have not yet received treatment with a Janus kinase (JAK) inhibitor.

Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia

A Phase 2, Open-label, Randomized Study to Evaluate the Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia

For the PV Cohort, overall response rate (ORR) is defined as the proportion of participants with all of the following at some point during the treatment period:

* Hematocrit \< 45% in the absence of phlebotomy that lasts at least 4 weeks
* White blood cell (WBC) count \< 10 x 10\^9/L that lasts at least 4 weeks
* Platelet count ≤ 400 x 10\^9/L that lasts at least 4 weeks
* Resolution of palpable splenomegaly that lasts at least 4 weeks

For the ET Cohort, overall response rate is defined as the proportion of participants with all of the following at some point during the treatment period:

* WBC count \< 10 x 10\^9/L that lasts at least 4 weeks
* Platelet count ≤ 400 x 10\^9/L that lasts at least 4 weeks
* Resolution of palpable splenomegaly that lasts at least 4 weeks

Confirmed overall response rate is defined as the proportion of participants who meet all the criteria listed for the primary endpoints of PV or ET, sustained for at least 12 weeks.

Sierra Oncology LLC - a GSK company

Digestive System Diseases

Carcinoma

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Hematinics

Liver Extracts

Patients with synchronous colorectal liver metastases who underwent surgical resection

Blood samples were drawn by expert phlebotomists in vacuum blood tubes containing K2-EDTA (Terumo Europe NV, Leuven, Belgium). The complete blood cell count (CBC) was performed using Advia 2120 (Siemens Healthcare Diagnostics, Tarrytown NY, USA). The local reference range for platelets was 150-400 x 109/L. The same analyser was used throughout the study period, and the quality and reproducibility of test results was validated by data of both internal quality control and external quality assessment

Measurement of platelet count at diagnosis

Corrado Pedrazzani, MD

Colorectal cancer (CRC) is the third most common malignancy worldwide and is often metastatic at diagnosis. Despite progresses in surgical techniques and the introduction of novel chemotherapy regimens, many patients still suffer from a poor prognosis. It is therefore of utmost importance to identify prognostic markers that may improve selection of patients.

In recent years several studies demonstrated that preoperative blood tests as platelet count or neuthophil-to-lymphocyte ratio could be prognostic factors in CRC as well as other malignancies. The aim of this study was to evaluate the role of preoperative platelet count (PC) in patients with synchronous colorectal liver metastases.

Elevated Platelet Count as Prognostic Factor in Colorectal Cancer With Synchronous Liver Metastases

Elevated Platelet Count as Prognostic Factor in Colorectal Cancer With Synchronous Liver Metastases: a Retrospective Single-center Cohort Study

correlation between high PC and overall survival

correlation between high PC and clinic-pathological variables

Azienda Ospedaliera Universitaria Integrata Verona

Principal Investigator

Vascular Diseases

Janus Kinase Inhibitors

LDE225

INC424

Novartis Pharmaceuticals

The purpose of this phase Ib/II clinical trial was to: a) evaluate the safety of the co-administration of LDE225 and INC424 in myelofibrosis patients and establish a maximum tolerated dose and/or Recommended Phase II dose of the combination and b) to assess the efficacy of the co-administration of LDE225 and INC424 on spleen volume reduction.

The study is considered to have been completed because the participants completed the study as per study design at the time of trial termination. If participants were already in extension phase until discontinuation criteria were met or alternative setting was available, they were considered as completed. The study was terminated due to one of the compounds being divested.

A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF

A Phase Ib/II, Open-label, Multi-center, Dose-finding Study to Assess the Safety and Efficacy of the Oral Combination of LDE225 and INC424 (Ruxolitinib) in Patients With Myelofibrosis

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.

A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.

Reduction in spleen volume as measured by magnetic resonance imaging/Cat Scan (MRI/CT) in Phase Ib expansion and Phase II Stage 1 patients

Plasma Concentration Time Curve: AUC0-24h: Area under the concentration-time curve from time zero to 24 hours extrapolate from AUClast\[mass x time x volume-1\]

AUC0-12h: Area under the concentration-time curve from time zero to 12 hours extrapolate from AUClast\[mass x time x volume-1\]. AUCinf: Area under the concentration-time curve from time zero to infinity with extrapolation of the terminal phase \[mass x time x volume-1\]. AUClast: Area under the concentration-time curve from time zero to the time of last measurable concentration \[mass x time x volume-1\].

Cmax: Maximum observed plasma concentration after drug administration \[mass x volume-

1\].

CL/F: Apparent total plasma clearance of drug after oral administration \[volume x time-1\]

The number of patients experiencing improvement in their bone marrow fibrosis by at least one grade and assessment of cellularity.

Phase Ib and Phase ll: Change in Pharmacodynamic Biomarkers: JAK2V617F allele burden

Summary of cytokine levels in Pharmacodynamic Biomarkers for all 26 collected at Week 25 Day 1 and Week 49 Day 1

The 7-day modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 is a 7-item PRO instrument based on the modified MFSAF v2.0 diary administered at specified visits. The first 6 items assess MF symptom severity at its worst as recalled in the 7 days prior to the clinic visit assessment. The symptoms measured include night sweats, itching, abdominal discomfort, pain under the ribs (left side), early satiety, \& bone/muscle pain. The 7th item captures MF-related inactivity in the past 7 days prior to the clinic visit assessment. All 7 items ask subjects to record their answers on an 11-point numeric rating scale (NRS), (0 = Absent, 10 = Worst Imaginable). The first 6 items of the instrument focus on MF symptoms \& are summed to create a Total Symptom score.

EORTC QLQ-C30 is the European Organization for Research \& Treatment of Cancer, Quality of Life (QoL) Questionnaire \& is one of the most widely used \& validated instruments to measure health-related QoL in subjects with cancer. The scale includes 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning \& social functioning), global health status/QoL \& 9 symptom scale/items (fatigue, nausea \& vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, \& financial difficulties). This instrument asks the subject to respond according to the past week, with the exception of the first 5 questions that represent physical functioning \& capture the subject's current status. The range of scores for all of the scales is from 0 to 100. For functional \& global health status/QoL scales, higher scores indicate better QoL \& level of functioning; for symptom scales, higher scores indicate greater level of symptoms or difficulties.

Racc: Accumulation ratio calculated as AUC0-12h on Week 9 Day 1 divided by AUC0-12h on Week 1 Day 1 \[fold\]

T1/2: Elimination half-life associated with the terminal slope (lambda_z) of a semi logarithmic concentration-time curve \[time\]

Vss/F: Apparent volume of distribution at steady state after oral administration \[volume\]

Participants who took a combination of LDE225 400mg and INC424 10mg in the dose escalation phase

LDE225 400 mg + INC424 10 mg

Participants who took a combination of LDED225 400mg and INC424 15mg in the dose escalation phase

LDE225 400 mg + INC424 15 mg

Participants who took a combination of LDED225 400mg and INC424 20mg in the dose escalation phase

LDE225 400 mg + INC424 20 mg

Participants who took a combination of LDED225 400mg and INC424 20mg in the dose expansion phase

LDE225 400 mg + INC424 20 mg (Dose Expansion)

All Patients

Participants who took a combination of LDE225 400mg and INC424 10mg in the dose escalation phase.

LDE225 400mg + INC424 10 mg (Dose Escalation Phase)

LDE225 400mg + INC424 15 mg (Dose Escalation Phase)

Participants who took a combination of LDE225 400mg and INC424 20mg in the dose escalation phase.

LDE225 400mg + INC424 20mg (Dose Escalation Phase)

LDED225 400mg + INC424 20mg (Dose Expansion Phase)

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Please refer to detailed description regarding reason for early termination of study.

Study Director

LDE225 400mg + INC424 10mg (Dose Escalation Phase)

LDE225 400mg + INC424 15mg (Dose Escalation Phase)

Safety Analysis Set (SAS) included all participants in Phase Ib \& Phase II who received at least 1 dose of LDE225 and/or INC424 \& had at least 1 valid post-baseline safety assessment. DLT was measured in the Phase Ib dose escalation \& expansion phase, as part of the primary outcome. All participants in the safety set were considered for toxicities.

Number of Participants With Dose Limiting Toxicities (DLTs) (Phase 1b)

Week 24

Week 48

The Full Analysis Set (FAS) comprised all subjects in Phase Ib and Phase II who received at least one dose of LDE225 and/or INC424. The data disclosed includes only participants from Phase Ib dose expansion phase and Ph II Stage 1. This data does not include dose escalation Phase Ib participants.

Percentage of Patients Achieving >= 35% Reduction in Spleen Volume in Phase Ib Expansion and Phase II Stage 1

LDE225 (Week 1, Day 1) (n=6,10,4,24)

LDE225 (Week 9, Day 1) (n=6,6,4,14)

The Pharmacokinetic Analysis set (PAS) consisted of all subjects in Phase Ib and Phase II who received at least one (full or partial) dose of LDE225 and/or INC424 and provided at least one evaluable PK blood sample for LDE225 and/or INC424.

Phase Ib and Phase II: LDE225: Plasma Pharmacokinetics (PK) Parameter: Area Under the Curve(AUC0-24h)

AUC0-12h: Wk1 Day 1 (n=8,10,5,25)

AUC0-12h: Wk 9 Day 1 (n=8,9,4,20)

AUCinf: Wk1 Day 1 (n=7,9,4,16)

AUCinf: Wk 9 Day 1 (n=8,9,3,15)

AUClast: Wk1 Day 1 (n=8,10,5,26)

AUClast: Wk 9 Day 1 (n=8,9,4,20)

Phase Ib and Phase II: INC424: PK Parameters: Area Under the Curve for AUC0-12h, AUCinf & AUClast

LDE225 (Week 1, Day 1) (n=6,10,5,26)

LDE225 (Week 9, Day 1) (n=8,8,5,20)

INC424 (Week 1, Day 1) (n=8,10,5,27)

INC424 (Week 9, Day 1) (n=8,9,4,20)

The pharmacokinetic analysis set (PAS) consisted of all subjects in Phase Ib and Phase II who received at least one (full or partial) dose of LDE225 and/or INC424 and provided at least one evaluable PK blood sample for LDE225 and/or INC424.

Phase Ib and Phase II: LDE225 & INC424: PK Parameter: Maximum Plasma Concentration (Cmax)

Phase Ib and Phase II: LDE225 & INC424: Plasma PK Parameter: Time to Maximum Plasma Concentration (Tmax)

LDE225 (Week 1, Day 1) (n=5,5,1,12)

INC424 (Week 1, Day 1) (n=7,9,4,16)

INC424 (Week 9, Day 1) (n=0,0,0,0)

Phase Ib and Phase II: LDE225 & INC424:: Plasma Pharmacokinetics (PK) Parameters: Area Under the Curve(CL/F)

Baseline, grade 0 (n=0,0,0,1)

Baseline, grade 1 (n=0,1,0,4)

Baseline, grade 2 (n=4,6,3,8)

Baseline, grade 3 (n=3,3,0,8)

Baseline, missing grade (n=1,0,2,6)

Week 25 Day 1, grade 1 (n=1,1,0,1)

Week 25 Day 1, grade 2 (n=0,3,2,7)

Week 25 Day 1, grade 3 (n=5,4,1,5)

Week 25 Day 1, missing grade (n=2,2,2,14)

Week 49 Day 1, grade 0 (n=0,0,0,1)

Week 49, Day 1 grade 1 (n=0,0,0,1)

Week 49 Day 1, grade 2 (n=0,1,1,2)

Week 49 Day 1, grade 3 (n=2,2,2,3)

Week 49 Day 1, missing grade (n=6,7,2,20)

The Full Analysis Set (FAS) comprised all subjects in Phase Ib and Phase II who received at least one dose of LDE225 and/or INC424.

Phase Ib and Phase II: Percentage of Participants With Fibrosis Grade Assessed by Bone Marrow Histomorphology, by Time and Treatment in Phase Ib and Phase II Stage 1

Baseline

Week 25 Day 1 (n=7,6,5,21)

Week 49 Day 1 (n=4,3,4,13)

The Biomarker Analysis Set (BAS) consisted of all subjects in Phase Ib and Phase II who received at least one (full or partial) dose of LDE225 and/or INC424 and provided at least one evaluable biomarker sample.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Interest of CALR Allele Burden in Diagnosis and Follow-up of Patients With CALR Mutated Myeloproliferative Syndromes (CALRSUIVI)	NCT04942080	Myeloproliferat... Essential Throm... Primary Myelofi... Primary Myelofi...	CALR allele bur...	18 Years -	University Hospital, Angers
Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia	NCT01998828	Polycythemia Ve... Essential Throm...	Momelotinib	18 Years -	Sierra Oncology LLC - a GSK company
Elevated Platelet Count as Prognostic Factor in Colorectal Cancer With Synchronous Liver Metastases	NCT03717519	Colorectal Canc... Colorectal Carc... Stage IV Colon ...	Measurement of ...	18 Years - 100 Years	Azienda Ospedaliera Universitaria Integrata Verona
A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients With MF	NCT01787552	Primary Myelofi... Thrombocytosis Essential Throm... Polycythemia Ve... Myeloproliferat... Bone Marrow Dis... Hematologic Dis... Blood Coagulati... Blood Platelet ... Hemorrhagic Dis...	LDE225 INC424	18 Years -	Novartis
Open Label Ruxolitinib (INCB018424) in Patients With Myelofibrosis and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis	NCT00509899	Myelofibrosis Polycythemia Ve... Thrombocytosis	Ruxolitinib	18 Years -	Incyte Corporation
Open Label Ruxolitinib (INCB018424) in Patients With Myelofibrosis and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis	NCT00509899	Myelofibrosis Polycythemia Ve... Thrombocytosis	Ruxolitinib	18 Years -	Incyte Corporation
Interest of CALR Allele Burden in Diagnosis and Follow-up of Patients With CALR Mutated Myeloproliferative Syndromes (CALRSUIVI)	NCT04942080	Myeloproliferat... Essential Throm... Primary Myelofi... Primary Myelofi...	CALR allele bur...	18 Years -	University Hospital, Angers
Leading in MPNs Beyond Ruxolitinib in Combo With T-Regs	NCT05423691	Myelofibrosis	CK0804	18 Years -	Cellenkos, Inc.
Interest of CALR Allele Burden in Diagnosis and Follow-up of Patients With CALR Mutated Myeloproliferative Syndromes (CALRSUIVI)	NCT04942080	Myeloproliferat... Essential Throm... Primary Myelofi... Primary Myelofi...	CALR allele bur...	18 Years -	University Hospital, Angers

Spots Global Cancer Trial Database for thrombocytosis