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

Immune System Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasm Metastasis

Graft vs Host Disease

Neoplasms by Histologic Type

Neoplastic Processes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Homologous Wasting Disease

Acute Graft Versus Host Disease

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Amino Acids

Tacrolimus

Fludarabine

Fludarabine phosphate

Melphalan

Sirolimus

Mechlorethamine

Nitrogen Mustard Compounds

Temsirolimus

MTOR Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Phenylalanine

Alanine

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV on days -9 to -5 and melphalan IV over 20 minutes on day -4. Beginning greater than 48 hours after completion of melphalan, patients undergo peripheral blood stem cell or bone marrow transplant according to standard guidelines on day 0.

GVHD PROPHYLAXIS: Patients receive ruxolitinib phosphate PO BID on days -3 to 30 tapered to day 60, tacrolimus IV continuously or PO BID on days -3 to 100 , and sirolimus PO QD on day -3 to 100. Treatment continues in the absence of disease progression or unacceptable toxicity.

Undergo allogeneic bone marrow transplant

Allogeneic Bone Marrow Transplantation

Undergo allogeneic hematopoeitic stem cell transplant

Allogeneic Hematopoietic Stem Cell Transplantation

Fludarabine Phosphate

Laboratory Biomarker Analysis

Undergo hematopoietic stem cell transplant

Peripheral Blood Stem Cell Transplantation

Pharmacological Study

Ruxolitinib Phosphate

Haris Ali

This phase I trial studies the side effects and best dose of ruxolitinib phosphate when given together with tacrolimus and sirolimus in preventing acute graft-versus-host disease during reduced intensity donor hematopoietic cell transplant in patients with myelofibrosis. Sometimes transplanted cells from a donor can attack the normal tissue of the transplant patient called graft-versus-host disease. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It may also reduce graft-versus-host disease by reducing inflammation and immune modulation. Giving ruxolitinib phosphate together with tacrolimus and sirolimus after transplant may prevent graft-versus-host disease.

PRIMARY OBJECTIVES:

I. Among the dose levels tested, to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of ruxolitinib (ruxolitinib phosphate), when given in combination with tacrolimus and sirolimus (TAC/SIR) as acute graft-versus-host disease (aGVHD) prophylaxis as part of reduced intensity allogeneic hematopoietic cell transplant (HCT), in patients with myelofibrosis or other related myeloid neoplasm with marrow fibrosis.

SECONDARY OBJECTIVES:

I. To determine if the addition of ruxolitinib, to the standard aGVHD prophylactic regimen of TAC/SIR, is safe by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.

II. To estimate the cumulative incidence of aGVHD and non-relapse mortality (NRM) at 100-days post transplant.

III. To estimate the cumulative incidence of chronic GVHD at 1- and 2-years post transplant.

IV. To characterize and evaluate hematologic recovery, donor cell engraftment and immune reconstitution by cell count and flow cytometry of lymphocyte subsets.

V. To estimate the probabilities of overall and progression-free survival (OS/PFS) at 1- and 2-years post transplant.

VI. To characterize changes in aGVHD biomarkers (regenerating islet-derived 3-alpha \[Reg-3alpha\], soluble tumor necrosis factor receptor I \[sTNF RI\], interleukin 2 receptor alpha \[IL2Ralpha\]), Janus-associated kinase (JAK)-regulated pro-inflammatory cytokines (i.e. interleukin \[IL\]-6, tumor necrosis factor \[TNF\] alpha, C-reactive protein \[CRP\], beta 2 microglobulin) and signal transducer and activator of transcription 3 (STAT3) phosphorylation (downstream of JAK signaling) over time and by aGVHD status/grade.

OUTLINE: This is a dose-escalation study of ruxolitinib phosphate.

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -9 to -5 and melphalan IV over 20 minutes on day -4. Beginning greater than 48 hours after completion of melphalan, patients undergo peripheral blood stem cell or bone marrow transplant according to standard guidelines on day 0.

GVHD PROPHYLAXIS: Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days -3 to 30 tapered to day 60, tacrolimus IV continuously or PO BID on days -3 to 100 , and sirolimus PO once daily (QD) on day -3 to 100. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up 2 years.

Ruxolitinib Phosphate, Tacrolimus and Sirolimus in Preventing Acute Graft-versus-Host Disease During Reduced Intensity Donor Hematopoietic Cell Transplant in Patients With Myelofibrosis

A Phase I Trial of Ruxolitinib Combined With Tacrolimus and Sirolimus as Acute Graft-versus-Host Disease (aGVHD) Prophylaxis During Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis

Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

The first day of acute GVHD onset at a certain grade will be used to calculate the cumulative incidence (grades II-IV). Calculated using the Gray method with prior death or relapse considered competing events.

For all cytokines/biomarkers that are measured repeatedly over time, a nonparametric smoothing plot will be produced in the first step to view changes in the trend. Expression level changes on the onset of aGVHD from baseline measures will be correlated with aGVHD grade (0-1 vs 2-4 or 0-2 vs 3-4). Furthermore, GVHD biomarkers, Reg-3a, TNF R1, and a composite biomarker panel of 4 proteins (IL-2Ra, TNFR1, IL-8, and hepatocyte growth factor) will be correlated with survival outcomes in a continuous manner or dichotomized manner.

The first day of chronic GVHD onset will be used to calculate the cumulative incidence. Calculated using the Gray method with prior death or relapse considered competing events.

Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any.

The cumulative incidence of relapse/progression and non-relapse mortality will be calculated as competing risks using the Gray method. Descriptive statistics will also be used to assess the possible relationship between pre-HSCT disease status and outcomes. As the results of these evaluations are considered hypothesis-generating in nature, the statistics used will not include any formal statistical tests/comparisons.

Estimate will be calculated using the Kaplan-Meier method.

The cumulative incidence of relapse/progression and non-relapse mortality will be calculated as competing risks using the Gray method. Descriptive statistics will also be used to assess the possible relationship between pre-hematopoietic stem cell transplant (HSCT) disease status and outcomes. As the results of these evaluations are considered hypothesis-generating in nature, the statistics used will not include any formal statistical tests/comparisons.

National Cancer Institute (NCI)

City of Hope Medical Center

Polycythemia Vera

Polycythemia

Bone Marrow Neoplasms

Hematologic Neoplasms

Harinder Gill, MD

Garret Leung, MD

Yok-lam Kwong, MD

This is a multinational, multicenter, prospective and retrospective, observational, cohort study of patients with myeloproliferative neoplasm.

This is a multinational, multicenter, prospective and retrospective, observational, cohort registry of patients with MPN. The registry mainly involves study centres in Asia including but not limited to Hong Kong, Singapore, Malaysia, Taiwan, Korea and Thailand. Clinicopathologic characteristics, cytogenetic characteristics, mutational characteristics, treatment characteristics, outcomes and survivals of Asian patients MPN diagnosed between 2010-2025 will be collected to establish clinical registry.

Data on the clinicopathologic characteristics, cytogenetics, mutational profile, prognostic scoring treatment characteristics, responses to treatment, outcome and survivals will be collected through routine clinic visits and/or reviewing medical records. Data will be collected at diagnosis, and approximately every 6 months thereafter (for prospective data) and at progression until death/study termination.

Peripheral blood and bone marrow aspirate

Asian Myeloproliferative Neoplasm (MPN) Registry

Asian Myeloproliferative Neoplasm (MPN) Registry - An Asian Myeloid Working Group (AMWG) Project.

Measured in months, from date of diagnosis of MPN to date of documentation of secondary myelofibrosis (event), death (event) or latest follow-up (censor). Patient without an event will be censored at date last known to be progression-free

Measured in months, from date of diagnosis of MPN to the date of the first MDS or AML or death due to any cause. Patient without an event will be censored at date last known to be progression-free and alive.

Measured in months from the date of diagnosis of MDS until the date of death due to any cause. Patient who is alive will be censored at the date last known alive

Novartis

The University of Hong Kong

* spleen fibrosis by elastography
* plasma cytokines levels
* mutationnal landscape by NGS
* CD34 circulating cells

Non-invasive diagnosis score

Damien Luque Paz, Pharm.D.

Corentin Orvain, M.D.

Damien Luque Paz

Corentin Orvain

Jean-Christophe Ianotto

Eric Lippert

Prospective study for the development of a non-invasive score for differentiating prefibrotic myelofibrosis from essential thrombocytosis and overt myelofibrosis.

The diagnostic criteria for myeloproliferative neoplasia have recently been revised in the WHO 2016 classification, which now recognizes a new entity between essential thrombocythemia (TE) and overt myelofibrosis (or primary myelofibrosis): prefibrotic myelofibrosis. Prefibrotic myelofibrosis patients seem to have a poorer prognosis compared to essential thrombocythemia in term of overall survival and myelofibrotic evolution. The dichotomy between these diseases is based on the bone marrow biopsy evaluation and is challenging with a lack of reproducibility showed in the literature.

This study aims to develop a diagnostic non-invasive score for differentiating prefibrotic myelofibrosis from essential thrombocytosis and overt myelofibrosis.

The parameters studied are :

* spleen fibrosis by elastography
* plasma cytokines levels
* mutationnal landscape by NGS
* CD34 circulating cells

Bone marrow biopsy were reviewed by 2 anatomopathologists. Number of patients to be enrolled : 130

Pilot Study for the Development of a Diagnostic Score to Differentiate Myeloproliferative Neoplasms.

Pilot Study for the Development of a Non-invasive Diagnostic Score to Differentiate Between Essential Thrombocythemia, Premyelofibrosis and Myelofibrosis

Data of study protocol, Statiscal analysis plan and the infromed consent form will be made available after the study completion

Assessment of the non-invasive diagnostic score against the WHO diagnosis

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
Ruxolitinib Phosphate, Tacrolimus and Sirolimus in Preventing Acute Graft-versus-Host Disease During Reduced Intensity Donor Hematopoietic Cell Transplant in Patients With Myelofibrosis	NCT02528877	Acute Myeloid L... Primary Myelofi... Primary Myelofi... Secondary Acute... Secondary Myelo...	Allogeneic Bone... Allogeneic Hema... Fludarabine Pho... Laboratory Biom... Melphalan Peripheral Bloo... Pharmacological... Ruxolitinib Pho... Sirolimus Tacrolimus	18 Years - 75 Years	City of Hope Medical Center
Asian Myeloproliferative Neoplasm (MPN) Registry	NCT05882773	Myeloproliferat... Polycythemia Ve... Essential Throm... Post-polycythem... Post-essential ... Primary Myelofi... Primary Myelofi... Primary Myelofi...		18 Years -	The University of Hong Kong
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
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
Pilot Study for the Development of a Diagnostic Score to Differentiate Myeloproliferative Neoplasms.	NCT03869476	Myeloproliferat... Essential Throm... Primary Myelofi... Primary Myelofi...	Non-invasive di...	18 Years - 99 Years	University Hospital, Angers

Spots Global Cancer Trial Database for primary myelofibrosis, prefibrotic stage