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

Gastrointestinal Agents

All Drugs and Chemicals

Antineoplastic Agents

Antisickling Agents

Fibrinolytic Agents

Platelet Aggregation Inhibitors

Calcium Carbonate

Hydroxyurea

Anagrelide

Ropeginterferon alfa-2b (P1101) dosage: from 250 mcg to 500 mcg

Ropeginterferon alfa-2b

Anagrelide dosage: 0.5 mg per capsule, according to label and physician's judgement

Toshiaki Sato, MD/PhD

Craig Zimmerman, PhD

This is a Phase 3 open-label, multicenter, randomized, active-controlled study designed to compare the efficacy and safety and tolerability of P1101 compared with ANA after 12 months of treatment as second-line therapy for subjects with ET who have had a suboptimal or failed response to HU.

PharmaEssentia Corporation is developing a pegylated (PEG) IFN-α product, P1101, for the treatment of ET.

Available clinical data and experience with P1101 in PV shows that the compound, with proper dose modifications, is effective in controlling disease in a significant proportion of subjects with ET. Further, its increased serum half-life presents distinct advantages for ET treatment over that of standard IFN-α and other available PEG IFN-α therapy. This pivotal Phase 3 study will establish the efficacy and safety of P1101 in ET subjects.

In core study phase, the enrolled subjects will be randomized into two arms, the test arm is P1101, the control arm is ANA. The overall duration for each eligible patient is 14 months, including screening (1 month), treatment (12 months) and follow-up (1 month) period. Efficacy evaluations, safety assessments, and PK and immunogenicity evaluations of P1101 will be performed.

Evaluation of efficacy will include clinical laboratory assessments, allelic burden measurements of CALR, JAK-2, and MPL, spleen size measurements, bone marrow sampling, EQ-5D-3L, and MPN-SAF TSS completion.

Evaluation of safety will include assessing vital signs, clinical safety laboratory tests, physical examinations, ECG evaluation, heart ECHO, lung X-ray, ECOG performance status, ocular examination, and AEs.

Subjects who completed the end of treatment (EoT) and safety follow-up (EoS) visits of the SURPASS ET study and may benefit from P1101 therapy have the opportunity to receive P1101 treatment.

Experimental Drug (Biological): Ropeginterferon alfa-2b (P1101), Q2W, SC injection Control Drug: Anagrelide, capsules, daily, p.o.

Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance

A Phase 3, Open-Label, Multicenter, Randomized, Active-controlled Study to Assess PK and Compare the Efficacy, Safety, and Tolerability of P1101 vs Anagrelide as 2nd Line Therapy for Essential Thrombocythemia (SURPASS ET): The Core Study and Its Extension Study.

platelets ≤400 x 10\^9/L AND white blood cells (WBC) \<9.5 x 10\^9/L

based on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

absence of hemorrhagic or thrombotic events

PharmaEssentia

Anti-Infective Agents

Vaccines

Poly ICLC

Interferons

Immunologic Factors

peptide-based vaccine in patients with myeloproliferative neoplasm (myelofibrosis and essential thrombocythemia) with CALR mutations

ten (10) doses of Mutant-CALR peptides with KLH as helper peptide (in the first vaccine only). Mutant-CALR vaccine will administered every 2 weeks for the first 4 doses and then every 4 weeks for additional 6 doses. Maintenance Treatment The protocol allows for a continued administration of up to four (4) additional Mutant-CALR vaccine and four (4) Poly-ICLC administrations, 12 weeks apart.

Peptide-based vaccine

ten (10) doses of Poly-ICLC. Poly-ICLC will be given on weeks 1, 3, 5, 7, 11, 15, 19, 23, 27 and 31. each Poly-ICLC dose must be given the day after the corresponding Mut-CALR vaccination.

Marina Kremyanskaya, MD, PhD

Mikaela Dougherty

Mikaela Dougherty, BS

Nina Bhardwaj, MD, PhD

Camelia Iancu-Rubin, PhD

The primary objective of this study is to assess the safety and tolerability of administrating mutated-CALR peptide Vaccine to patients with MPN. The researchers plan to enroll 10 patients over a 12 month period. Maximum length of participation in 80 weeks. Patients will be asked to complete questionnaires, bone marrow biopsies, research lab collection, and standard of care lab draw. This research will be taking place only at The Mount Sinai Hospital, specifically at the Ruttenberg Treatment Center.

Current MPN treatments are geared towards symptom palliation and not on changing the natural course of the disease. Mutations in calreticulin gene (CALR) is the second most common driver mutation in ET and MF patients (30%). All CALR mutations identified to date in MPN patients result in the formation of an altered protein with an identical 36-amino acid sequence in the C-terminus. This altered protein results in a MPN-specific shared neo-antigen. The mutated CALR neoantigen present in patient with MPN represents an ideal antigen for targeted immunotherapy as it is stably and specifically expressed by the malignant cells and is absent in the normal tissues. CALR neoantigen is immunogenic, effector T cells are capable of recognizing this neo-antigen, and hematopoietic cells carrying the mutation can be potently killed by these specific effector T-cells in vitro.

The researchers believe that a mutated-CALR vaccine will enhance mutated-CALR-specific T cell immunity in MPN patients carrying CALR mutations, which in turn would target and eliminate CALR+ malignant cells, thereby leading to improved clinical outcomes in this patient population.

Mutant CALR-peptide Based Vaccine in Patients With Mutated CALR Myeloproliferative Neoplasm

A Phase I Open Label Peptide Based Vaccine in Patients With Myeloproliferative Neoplasm Harboring CALR Mutations

The Dose Limiting Toxicity (DLT) rate, defined as the proportion of patients with at least 1 grade 3 or higher AE considered to be at least possibly related to the treatment with Poly ICLC and CALR vaccines.

The type, incidence, severity, seriousness, and relatedness of adverse events (AEs) per NCI CTCAE v5.0.

Number of observations, severity, and relatedness of clinical laboratory tests (hematology, biochemistry)

Changes in the immune milieu (which is a composite of expression of cytokines, presence of antibodies, alterations in number and phenotype of immune cells and induction of vaccine-specific T cell response) due to the vaccines as compared to baseline values.

The % change in driver mutation burden (CALR VAF) as compared to baseline

The proportion of patients who normalize their platelet number and/or achieve platelets less than 600 if started with platelet above 600.

The proportion of patients achieving response or improvement in their disease status by ELN/IWG criteria for the categories: Complete Response; Partial Response; Clinical Improvement and Stable Disease

The proportion of patients who achieve improvement in quality of life as assessed by the by the Myelofibrosis Symptom Assessment Form. Each of the items are scored 0 to 10, with total score from 0 to 100, with higher score indicating more symptoms.

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
Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance	NCT04285086	Essential Throm...	Ropeginterferon... Anagrelide	18 Years -	PharmaEssentia
Ropeginterferon Alfa-2b (P1101) vs. Anagrelide in Essential Thrombocythemia Patients With Hydroxyurea Resistance or Intolerance	NCT04285086	Essential Throm...	Ropeginterferon... Anagrelide	18 Years -	PharmaEssentia
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
Mutant CALR-peptide Based Vaccine in Patients With Mutated CALR Myeloproliferative Neoplasm	NCT05025488	Myelofibrosis Essential Throm... MPN	Peptide-based v... Poly ICLC	18 Years -	Icahn School of Medicine at Mount Sinai

Spots Global Cancer Trial Database for calr

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

Spots Global Cancer Trial Database for calr

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

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