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18F-FLT (PET/CT) in Prefibrotic/Early Primary Myelofibrosis and Essential Thrombocythemia (PMF/ET-FLT)

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ClinicalTrials.gov Identifier: NCT03116542
Recruitment Status : Recruiting
First Posted : April 17, 2017
Last Update Posted : August 2, 2018
Sponsor:
Information provided by (Responsible Party):
Hamad Medical Corporation

Brief Summary:

The main purpose of this project is to study the uptake pattern of FLT-PET in cases, and it is value in assessing the malignant hematopoiesis in cases of Pre-PMF and ET, regarding diagnosis, staging and monitoring response to therapy. Identifying different patterns of uptake in patients with Pre-PMF and ET in various clinical settings.

Evaluating FLT-PET as a novel non-invasive technique in cases with Pre-PMF and ET, in comparison to the standard bone marrow biopsy about disease diagnosis, assessment of disease activity, detection of transformation, monitoring of treatment response and grading of fibrosis.Study the ability of FLT-PET to differentiate between Pre-PMF and ET.

the investigators also aim to examine the association of FLT-PET uptake patterns with different genetic makeup (JAK2 (Janus kinase 2), CALR (Calreticulin), MPL (myeloproliferative leukemia protein), or Triple negative disease) or allele burden in cases of Pre-PMF and ET.


Condition or disease Intervention/treatment Phase
Essential Thrombocythemia Primary Myelofibrosis, Fibrotic Stage Primary Myelofibrosis, Prefibrotic Stage Device: Diagnostic (18F-FLT PET/CT) Not Applicable

Detailed Description:

PET with fluorodeoxy glucose combined with computed tomography is a major tool for the diagnosis, staging, and monitoring of treatment response in clinical oncology. 3'-18Fluoro-3'-deoxy-L-thymidine (18F-FLT) is a PET radiotracer that quickly accumulates in proliferating cells and can be used to assess tumor cell proliferation in various cancers as PET radiotracer offers a non-invasive assessment of cell proliferation in vivo.

Myeloproliferative Neoplasms (MPNs) are clonal hematopoietic stem disorders characterized by high rate of effective proliferation of one or more cell lineage. MPNs are overlapping syndromes that can progress to fibrotic stage or evolute into acute leukemia. Preliminary results of a pilot study (5) suggested that this technique could be useful to assess bone marrow (BM) activity and extramedullary hematopoiesis in patients with Myelofibrosis (MF).

The current standard for follow- up of these patients is based on pathological markers (peripheral blood counts and/ bone marrow histomorphology) and molecular markers. Although, bone marrow examination could be considered as a standard gold method as it gives detailed information about cellularity, the morphology of each lineage, a degree of fibrosis, transformation and dysplastic features. However, many patients are reluctant to go for this invasive technique which precludes precise assessment of disease activity at the desirable frequencies. Non- invasive techniques which may act as the good clinical surrogate are lacking.

The objective of this study is to study the uptake pattern of FLT-PET in cases, and it is value in assessing the malignant hematopoiesis in cases of Pre-PMF and ET, regarding diagnosis, staging and monitoring response to therapy.

Identifying different patterns of uptake in patients with Pre-PMF and ET in various clinical settings.

Evaluating FLT-PET as a novel non-invasive technique in cases with Pre-PMF and ET, in comparison to the standard bone marrow biopsy about disease diagnosis, assessment of disease activity, detection of transformation, monitoring of treatment response and grading of fibrosis.

Study the ability of FLT-PET to differentiate between Pre-PMF and ET. the investigators also aim to investigate the association of FLT-PET uptake patterns with different genetic makeup (JAK2, CALR, MPL, or Triple negative disease) or allele burden in cases of Pre-PMF and ET.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Study of 18F-FLT Positron Emission Tomography/Computed Tomography (PET/CT) Imaging in Cases of Prefibrotic/Early Primary Myelofibrosis (PMF) and Essential Thrombocythemia (ET)
Actual Study Start Date : May 7, 2017
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: Diagnostic (18F-FLT PET/CT)
Patients undergo 18F-FLT (3'-18Fluoro-3'-deoxy-L-thymidine) PET/CT (Positron Emission Tomography/Computed Tomography) at baseline. No specific dietary restrictions or hydration are required for FLT-PET scans, however, patients will be urged to drink plenty of water before and after the PET studies. [18F] FLT will be prepared by the cyclotron core facility and assessed for quality control following "good manufacturing practice" criteria. The radiopharmaceutical will immediately be brought to the Molecular Imaging and Therapy Service Radiopharmacy for dispensation in the PET suite. For each scan, patients will receive approximately up to 370 MBq (target of 10 mCi) [18F] FLT by intravenous infusion.
Device: Diagnostic (18F-FLT PET/CT)
The tracer compound [F-18] FLT will be injected into the patient's veins in a small volume of normal saline solution. The PET scan data collection is started immediately and is continued for 2 hours.
Other Names:
  • 18F-FLT PET/CT
  • 3'-Deoxy-3'-(18F) Fluorothymidine
  • 3'-deoxy-3'-[18F]fluorothymidine
  • Fluorothymidine F 18




Primary Outcome Measures :
  1. Number of patients with 50% or more uptake of FLT-PET in patients with Prefibrotic/Early Primary Myelofibrosis (PMF) and Essential Thrombocythemia (ET) 12 months from the baseline [ Time Frame: 12 Months ]
    Evaluate the uptake of 3'-deoxy-3'-[18F] fluorothymidine (FLT) positron emission tomography/computed tomography (PET) imaging and it is value in assessing the malignant hematopoiesis in patients with Prefibrotic/Early Primary Myelofibrosis (PMF) and Essential Thrombocythemia (ET).


Secondary Outcome Measures :
  1. Reduction in at least 50% of the allele burden of different mutations (JAK-2, MPL, CALR) and its expression on FLT- PET uptake pattern 12 moths from the baseline [ Time Frame: 12 Months ]
    Effect of different mutations (JAK-2, MPL, CALR) expression and allele burden on FLT- PET uptake pattern



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Age 18 year old or above Patient accept to sign inform consent ECOG (Eastern Cooperative Oncology Group) performance less than or equal 2

  • Cases fulfilling WHO (World Health Organization) 2016 diagnostic criteria for PMF:

WHO criteria for prefibrotic/early primary myelofibrosis (prePMF)

Major criteria:

  1. Megakaryocytic proliferation and atypia, without reticulin fibrosis > grade 1*, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation and often decreased erythropoiesis
  2. Not meeting the WHO criteria for BCR-ABL1+ ((BCR-ABL = fusion gene from BCR (breakpoint cluster region gene/BCR gene product) and ABL (Abelson proto-oncogene)) CML (chronic myelogenous leukemia), PV (Polycythemia Vera), ET, myelodysplastic syndromes, or other myeloid neoplasms
  3. Presence of JAK2, CALR or MPL mutation or in the absence of these mutations, presence of another clonal marker**or absence of minor reactive BM reticulin fibrosis.

Minor criteria:

Presence of at least one of the following, confirmed in two consecutive determinations:

  1. Anemia not attributed to a comorbid condition
  2. Leukocytosis >11 x 109/L
  3. Palpable splenomegaly
  4. LDH (Lactate dehydrogenase) increased to above upper normal limit of institutional reference range.

Diagnosis of prePMF requires meeting all three major criteria, and at least one minor criterion **in the absence of any of the 3 major clonal mutations, the search for the most frequent accompanying gene mutations (e.g. ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, SF3B1) are of help in determining the clonal nature of the disease.

*** minor (grade 1) reticulin fibrosis secondary to infection, autoimmune disorder or other chronic inflammatory conditions, hairy cell leukemia or other lymphoid neoplasm, metastatic malignancy, or toxic (chronic) myelopathies

WHO diagnostic criteria essential thrombocythemia Major criteria Platelet count ≥450 × 109/L Bone marrow biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei. No significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibers.

Not meeting WHO criteria for BCR-ABL1+ CML, PV, PMF, myelodysplastic syndromes, or other myeloid neoplasms Presence of JAK2, CALR, or MPL mutation Minor criterion Presence of a clonal marker or absence of evidence for reactive thrombocytosis Diagnosis of ET requires meeting all 4 major criteria or the first 3 major criteria and the minor criterion

Exclusion Criteria:

  • Patient not fulfilling the inclusion criteria.
  • Vulnerable groups: pregnant, minors, prisoners will not be included.
  • Bone marrow will be collected as part of the routine diagnostic work-up. No extra bone marrow material will be collected solely for the aim of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03116542


Contacts
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Contact: Mohamed Yassin 55037393 yassin@hamad.qa
Contact: Abdulqadir Nashwan 66473549 anashwan@hamad.qa

Locations
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Qatar
National Center for Cancer Care & Research (NCCCR) Recruiting
Doha, Qatar
Contact: Mohamed Yassin       yassin@hamad.qa   
Contact: Abdulqadir Nashwan    66473549    anashwan@hamad.qa   
Sub-Investigator: HALIMA EL OMRI         
Sub-Investigator: Shehab F Mohamed         
Sub-Investigator: Omar M Ismail         
Sub-Investigator: Ahmad Al Sabbagh         
Sub-Investigator: Firyal Ibrahim         
Sub-Investigator: Dina S Soliman         
Sub-Investigator: Samah A Kohla         
Sub-Investigator: Sadek A Nehmeh         
Sub-Investigator: Lajos Szabados         
Sub-Investigator: Stefan Guhlke         
Principal Investigator: Mohamed A Yassin         
Sponsors and Collaborators
Hamad Medical Corporation

Publications:

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Responsible Party: Hamad Medical Corporation
ClinicalTrials.gov Identifier: NCT03116542     History of Changes
Other Study ID Numbers: 16287/16
First Posted: April 17, 2017    Key Record Dates
Last Update Posted: August 2, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Anti-Infective Agents
Primary Myelofibrosis
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Alovudine
Antiviral Agents