Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Polycythemia Vera

Polycythemia

Thrombocytosis

Thrombocythemia, Essential

Hematologic Neoplasms

Hematologic Diseases

Bone Marrow Neoplasms

Bone Marrow Diseases

Myeloproliferative Disorders

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

Antineoplastic Agents

Antisickling Agents

All Drugs and Chemicals

Hydroxyurea

Pharmaceutical form:capsule

Route of administration: oral

SAR302503

Clinical Sciences & Operations

Primary Objective:

* Dose Ranging Phase: To evaluate the efficacy of daily oral doses of 100, 200, and 400 mg SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for :

  * Inducing absence of phlebotomy and a hematocrit below 45% for a minimum of 3 months in patients with polycythemia vera, and
  * Reduction of platelet count to ≤400 x 10x9/L for a minimum of 3 months in patients with essential thrombocythemia.
* PV Dose Expansion Phase and ET Dose Ranging Phase (only 600 mg dose group): To evaluate the efficacy of daily oral SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for:

  * Inducing absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with PV, and
  * Reduction of platelet count to ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with ET.

Secondary Objectives:

* To evaluate the safety of SAR302503.
* To evaluate the efficacy of SAR302503 in patients with PV who are resistant or intolerant to hydroxyurea for inducing absence of phlebotomy eligibility.
* To evaluate the efficacy of SAR302503 in patients with ET who are resistant or intolerant to hydroxyurea for reduction of platelet counts.
* To evaluate the efficacy of SAR302503 in inducing complete and partial responses beginning at Day 1 of Cycle 6 visit through Cycle 8.
* To evaluate splenic response as measured by spleen volume using MRI or CT.
* To evaluate the pharmacokinetics of SAR302503 after single and repeat doses.
* To evaluate the pharmacodynamics of SAR302503 as measured by changes in JAK2V617F allele burden in patients with JAK2V617F mutation, and STAT3 phosphorylation inhibition.
* To measure improvement in baseline myeloproliferative neoplasm (MPN)-associated symptoms, as well as overall impact on quality of life.
* To measure generic health-related quality of life and utility value using the EuroQol Group (EQ-5DTM) questionnaire.

The duration of the study for an individual patient is at least 40 weeks and will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of up to 8, 28-day cycles (32 weeks), and a follow-up visit 30 days following the last administration of study drug. Treatment may continue if the patient is deriving benefit and does not experience disease progression, unacceptable toxicity, or meet other study withdrawal criteria.

Per Protocol Amendment No. 5, accrual of patients with essential thrombocythemia is closed.

Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia

A Randomized Phase II, Open-Label Study of the Efficacy and Safety of Orally Administered SAR302503 in Patients With Polycythemia Vera (PV) or Essential Thrombocythemia (ET) Who Are Resistant or Intolerant to Hydroxyurea

Sanofi

Primary Myelofibrosis

once daily in consecutive 28-day cycles, flexible dosing regimen (the starting dose is 400mg/day), orally, empty stomach, approximately same time each day

Primary Objective:

- To evaluate the efficacy of once daily dose of SAR302503 in subjects previously treated with ruxolitinib and with a current diagnosis of intermediate-1 with symptoms, Intermediate-2 or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (Post-PV MF), or post-essential thrombocythemia myelofibrosis (Post-ET MF) based on the reduction of spleen volume at the end of 6 treatment cycles;

Secondary Objectives:

* To evaluate the effect of SAR302503 on Myelofibrosis (MF) associated symptoms as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary
* To evaluate the durability of splenic response
* To evaluate the splenic response to SAR302503 by palpation at the end of Cycle 6
* To evaluate the splenic response to SAR302503 at the end of Cycle 3
* To evaluate the effect of SAR302503 on the Janus kinase 2 (JAK2) V617F allele burden
* To evaluate the safety and tolerability of SAR302503 in this population
* To evaluate plasma concentrations of SAR302503 for population PK analysis, if warranted

The expected duration of the treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a 6-month (6-cycle) treatment period, and an EOT visit for subjects who will not continue the treatment after completing the 6 cycles of SAR302503, or discontinue the treatment early for any reasons as well as a follow-up visit which should occur 30 days after the last administration of SAR302503. Patients who continue to benefit clinically will be allowed to remain on study medication beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib

A Phase II, Multicenter, Open Label, Single Arm Study of SAR302503 in Subjects Previously Treated With Ruxolitinib and With a Current Diagnosis of Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Symptoms and General Pathology

Splenomegaly

Primary Objective:

- To evaluate the efficacy of daily oral doses of 300 mg, 400 mg, and 500 mg SAR302503 for the reduction of spleen volume as determined by magnetic resonance imaging (MRI).

Secondary Objectives:

* To evaluate the safety of SAR302503.
* To evaluate the pharmacokinetics (PK) of SAR302503 after single and repeat doses.
* To evaluate the pharmacodynamics of SAR302503 as measured by changes in JAK2V617F allele burden in those patients with JAK2V617F mutation, changes in substrate phosphorylation in the JAK-STAT signal transduction pathway, and the expression of cytokines.
* To measure improvement in baseline Myeloproliferative Neoplasm (MPN) associated symptoms, as well as overall impact in quality of life (QOL), through serial administration of the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).
* To measure generic health-related quality of life (HRQL) and utility values using the EQ-5D questionnaire.

The duration of the study for an individual patient will include a period to assess eligibility (screening period 28 days), followed by a treatment period of at least 1 cycle (28 days) of study treatment, and an end-of-treatment visit at least 30 days following the last administration of study drug. However, treatment may continue if patients are deriving benefit and do not have unacceptable toxicity or meet study withdrawal criteria.

The study duration will be approximately 16 months which includes a 3-month enrollment period followed by a 12-month treatment period following the last patient enrolled followed by a 30-day follow-up period. The cut-off date for the analysis of the primary endpoint of response will be in maximum at the end of 3 months after the date of first dose of study drug of the last treated patient. The final analysis will be performed after the last enrolled patient completes the Cycle12 assessment.

Phase 2 Study of SAR302503 in Patients With Myelofibrosis

A Phase 2 Randomized, Open-Label, Dose-Ranging Study of the Efficacy and Safety of Orally Administered SAR302503 in Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly

Immune System Diseases

Graft vs Host Disease

Homologous Wasting Disease

Antirheumatic Agents

Pharmaceutical Solutions

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Micronutrients

Hematinics

Vitamins

Cyclophosphamide

Methotrexate

Cyclosporine

Cyclosporins

Lenograstim

Mycophenolic Acid

Mesna

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

GVHD prophylaxis will consist of high-dose PTCy (50 mg/kg i.v. on days +3 and +4) with mesna, cyclosporine (initiated on day +5) and methotrexate i.v (see doses on the right). Cyclosporine will be dosed with a target trough of 200 to 250 ng/mL and discontinued without taper at D+60 (if bone marrow graft) or until D+90 (is peripheral blood graft), unless acute GVHD is present. Filgrastim will be administered from day +5 until neutrophil recovery to ≥ 1,000/mcL for 3 days.

GVHD prophylaxis will consist of high-dose PTCy (50 mg/kg i.v. on days +3 and +4) with mesna, cyclosporine (initiated on day +5) and mycophenolate mofetil (15 mg/kg/dose p.o. t.i.d. initiated on day +5). Cyclosporine will be dosed with a target trough of 200 to 250 ng/mL and discontinued without taper at D+60 (if bone marrow graft) or until D+90 (is peripheral blood graft), unless acute GVHD is present.

Phase 1:

* Level -1: Methotrexate 7.5 mg/m2 on D+6 and D+9\*. Level -1 will be explored only if the starting dose is too toxic (reduced dose).
* Level 0 \[Starting Dose\]: Methotrexate 10 mg/m2 on D+6 and 7.5 mg/m2 on D+9
* Level +1: Methotrexate 10 mg/m2 on D+6 and D+9
* Level +2: Methotrexate 15 mg/m2 on D+6 and 10 mg/m2 on D+9

Phase 2: dose determined in the phase 1 trial

Methotrexate Injectable Solution

Giancarlo Fatobene, MD

Maria Claudia R Moreira, MD

Afonso Vigorito, MD, PhD

Iago Colturato, MD

Bruna Carvalho

Vanderson Rocha, MD, PhD

Allogeneic hematopoietic cell transplantation (HCT) is an important therapeutic strategy for many malignant and benign hematologic diseases. Haploidentical HCT has been increasingly used in patients lacking a HLA-matched donor due to its prompt availability, possibly lower cost and results comparable with other donor types. Graft-versus-host disease (GVHD) is the main cause of morbidity and mortality after HSCT, and prophylactic strategies are routinely used. In the context of haploidentical HCT, posttransplant cyclophosphamide plus cyclosporine and mycophenolate mofetil (MMF) is the most common platform used in Brazil. Data comparing MMF and methotrexate (MTX) as GVHD prophylaxes have proved controversial in other donor types, yet some large studies have showed that MTX is associated with lower risk of GVHD and improved long-term outcomes. Moreover, it is known that MMF is a potent inhibitor of natural killer (NK) cells, possibly interfering with the graft-versus-leukemia effect in haploidentical HCT. Given the possible advantages and the absence of consistent evidence regarding safety, efficacy and ideal dosage of MTX as GVHD prophylaxis in this setting, we propose a phase I / II study evaluating this drug in adult patients with hematologic malignancies undergoing haploidentical HCT with posttransplant cyclophosphamide.

Phase I / II multicenter open-label clinical trial with prospective nonrandomized arm and historical control group

GVHD Prophylaxis With Methotrexate in Haploidentical HCT Using Posttransplant Cyclophosphamide

GVHD Prophylaxis With Methotrexate and Cyclosporine in Haploidentical Stem Cell Transplantation Using Posttransplant Cyclophosphamide in Hematologic Malignancies: Phase I/II Trial

The methotrexate dose to be used in the subsequent phase 2 will be equal to or lower than the maximum tolerated dose (MTD). MTD will be considered exceeded if at least 2 out of 6 subjects on a certain dosing level develop dose-limiting toxicity (DLT). DLT consists of gastrointestinal tract perforation, mediastinitis, airway obstruction requiring orotracheal intubation, severe gastrointestinal bleeding (without evidence of GVHD), graft failure, or hyperbilirubinemia or increase in alanine transaminase \[ALT\] / aspartate transaminase \[AST\] levels \> 5x the upper limit of normal.

Relapse, grade 3-4 GVHD and 2014 NIH Chronic GVHD will be considered events, and non-relapse related mortality will be a competing event.

Neutrophil engraftment will be the first of three consecutive daily absolute neutrophil counts \> 500 / mcL after transplantation. Disease relapse will be a competitive event. Platelet engraftment will be considered as the first of seven daily consecutive platelet counts \> 20,000 / mcL without transfusion support. Disease relapse will be a competitive event.

Time to primary or secondary graft failure. Primary graft failure will be defined as failure to reach neutrophils \> 500 / mcL for three consecutive days or donor chimerism \<5% in any hematopoietic compartment (lymphocyte chimerism or total bone marrow / peripheral blood chimerism) and requiring additional hematopoietic cells. Secondary graft failure will be defined as the need for additional hematopoietic cells due to declining hematopoietic recovery in a patient with previous neutrophil engraftment.

Time to onset of grade II-IV acute GVHD according to the MAGIC criteria. Death without previous acute GVHD will be a competing event.

Time to onset of grade III-IV acute GVHD according to the MAGIC criteria. Death without previous acute GVHD will be a competing event.

Time to onset of disease relapse or progression (imaging, morphologic or molecular). Non-relapse related mortality will be a competing event.

Time to onset of 2014 NIH Chronic GVHD. Non-relapse related mortality will be a competing event.

Change in mean subscale response of the SF-36 Survey version 2.0 (Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Energy/fatigue, Emotional well-being, Social

Change in mean subscale response of the FACT-BMT survey

Adverse events will be classified according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 5.0

Libbs Farmacêutica LTDA

University of Sao Paulo General Hospital

once daily X 28 days, orally, empty stomach, approximately same time each day

Placebo

Primary Objective:

* To evaluate the efficacy of daily oral doses of 400 mg or 500 mg of SAR302503 (Investigational Medicinal Product, IMP) compared to placebo in the reduction of spleen volume as determined by magnetic resonance imaging (MRI) (or computed tomography scan in patients with contraindications for MRI).

Secondary Objectives:

* To evaluate the effect on Myelofibrosis (MF)-associated symptoms (key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary.
* To evaluate the Overall Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.
* To evaluate the Progression Free Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.
* To evaluate the durability of splenic response.
* To evaluate the safety of IMP.

The expected duration of a patient's treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a ≥6-month (6-cycle) treatment period, and an End Of Treatment (EOT) visit, which should be performed at least 30 days following the last administration of IMP or placebo.

Patients who continue to benefit clinically will be allowed to remain on IMP or placebo beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study of SAR302503 in Patients With Intermediate-2 or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly

This assessment will be conducted through the modified MFSAF diary, which will be completed during the week prior to Day 1 of each treatment cycle up to Cycle 6, and during the week prior to the end of Cycle 6.

Mouth and Tooth Diseases

Digestive System Diseases

Stomatitis

Xerostomia

Mucositis

Gastroenteritis

Gastrointestinal Diseases

Mouth Diseases

Stomatognathic Diseases

Salivary Gland Diseases

The protocol will be performed daily by a single trained professional from the first day of conditioning until D + 5 after bone marrow transplantation or while lesions are present.

PBMI protocol will use the indium-gallium-aluminium-phosphorus diode laser (InGaAlP) (DUO® - MMOptics Ltda, São Carlos, Brazil). Four anatomical areas will be irradiated perpendicularly in the buccal mucosa through several anatomical points with a distance of approximately 1 cm between them, in order to cover the largest area per cm² by region.

Application points:

* Buccal mucosa: 9 points each side: bite line on cheeks and upper and lower internal buccal vestibule (18 points).
* Tongue: 4 points on each side, on the lateral and ventral edge (8 points).
* Floor of the mouth: 1 point on each side (2 points)
* Upper and lower lips: upper and lower lips (lip redness), bottom of upper and lower sulcus and buccal commissure, right and left sides (4 points).
* Soft palate: right and left side (2 points)

The protocol will be performed daily by a single trained professional from the first day of conditioning until D + 5 after bone marrow transplantation or while lesions are present.

A gallium-aluminum arsenide diode laser (Gemini® manufactured by Azena Medical, LLC, distributed by Ultradent Products, Inc.) with double wavelength 810 + 980 nm, previously standardized and calibrated for extraoral application by the measurement of potency (Coherent Inc, Santa Clara, CA). The equipment will be programmed with 1 W of power. The application points will be carried out perpendicularly on the face.

Application points:

* 4 points on each cheek (2 on the right and 2 on the left)
* 1 on lips; patients with sealed lips being possible to cover the upper and lower lip
* 5 points in the cervical region (2 in the right submandibular space and 2 in the left submandibular space and submental space in the midline).

Intraoral photobiomodulation therapy (660nm, 100mW, 10 J/cm 2 , 3 s/point) for the management of oral side effects related during hematopoietic stem cell transplantation (HSCT). Mainly in the decrease of oral OM rates and OM severity, healing of OM ulcers and pain relief. Second, evaluate quality of life,hyposalivation/xerostomia, functional evaluation and dysfagia, in the arm. All results obtained in the group will be compared with the other arm.

Photobiomodulation therapy (intraoral)

Extraoral photobiomodulation therapy (810 + 980 nm, 1 W, 6.11 J/cm2 , 30 s/point) for the management of oral side effects related during hematopoietic stem cell transplantation (HSCT). Mainly in the decrease of oral OM rates and OM severity, healing of OM ulcers and pain relief. Second, evaluate quality of life,hyposalivation/xerostomia, functional evaluation and dysfagia, in the arm. All results obtained in the group will be compared with the other arm.

Photobiomodulation therapy (extraoral)

Manoela D Martins, PhD

Luan NS Kovalski, Msc

Fábio A Alves, PhD

Patients undergoing hematopoietic cell transplantation (HSCT) receive high doses of chemotherapy with or without radiotherapy to eradicate the underlying disease, which induces a series of adverse effects, including in the oral cavity. Among the most common oral lesions is oral mucositis (OM), which has been associated with greater morbidity and important biological and economic impact.Currently, photobiomodulation (PBM) with intraoral application has been recommended for the prevention of OM, however, few studies have evaluated the impact of its extraoral use.

The main objective of this study is to evaluate the effectiveness of extraoral PBM using unfocused high-power laser compared to intraoral PBM with low-power laser in the management of OM, mouth pain, functional capacity, development and duration of hyposalivation and xerostomia and quality of life. This is a multicenter, randomized, single blind clinical trial to be conducted at the Hospital de Clínicas de Porto Alegre (HCPA) and at the AC Camargo Cancer Center Hospital.

All patients who accept participate of the study will assign an informed consent form. For data management, the REDcap® software will be used, where all forms referring to patients evaluation will be incorporated. 42 patients will be selected who will undergo HSCT regardless of the underlying disease. Subsequently, upon accepting participation in the study, participants will undergo a sequential allocation using the R shiny summary statistics ® software by the variables of gender, age, type of HSCT and type of conditioning and will be allocated into 2 groups: Group I : intraoral photobiomodulation (660nm, 100mW, 10 J/cm 2 , 3 s/point) (PBMI, n=21) and Group II: extraoral photobiomodulation (810 + 980 nm,1 W,6.11 J/cm 2, 30 s/point) with high power extraoral unfocused laser with 1 W power (PBME, n=21). In both arms, the patients will receive photobiomodulation therapy from the the beginning of the conditioning until D + 5 after HSCT procedure. If any patient presenting or developing lesion after D + 5, this patient will receive the photobiomodulation protocol stipulated in your respective group util occur the healing of the lesion.

The study will be carried out by a dental surgeon who will carry out the initial assessment and reassessments (blinded to the groups) and another who will carry out the application of the PBM. Patients will be evaluated daily from the beginning of the conditioning until the bone marrow grafting or while there are oral lesions.

If they do not develop lesions, after bone marrow grafting, the patients will be evaluated weekly until hospital discharge. After clinical exam, grade and OM severity will be evaluated, after that, classified according WHO and NCI scale, pain assessment (VAS and NRS-101) and functional assessment, until D + 5 after HSTC procedure. The evaluation of xerostomia/hyposalivation (stimulated and non-stimulated salivary flow and xerostomia inventory) and quality of life will be performed in three moments, at the beginning of the conditioning, on the day of the HSCT and on the bone marrow marrow grafting day.

Saliva samples will be collected with SWABS, to futures microbioma analysis. The statistical analyzes will be carried out in the PASW 18.0 program, initially the evaluation of the data distribution will be carried out from the application of the Shapiro-Wilk and Kolmogorov-Smirnov tests.

If from the application of these tests, the data show normal distribution (p\>0.05), the t test will be used. If the distribution proves to be non-normal from the application of the test (p\<0.05), the Wilcoxon test will be used. The p-value will be set to 5%. Logistic regression will be used in fitted models to estimate the probability of occurrence of OM (dependent variable) in relation to clinical demographic variables (independent variables).

Patients will be randomized to one of two groups for the duration of the study. Group I (PBMI, n=21) photobiomodulation intraoral with a low potency laser, and Group II: photobiomodulation with high power extraoral unfocused laser with 1 W power (PBME, n=21).

The outcomes assessor will not know the laser protocol of each patient (single blind) .

Effectiveness of Extraoral Photobiomodulation in Management of Oral Adverse Effects in Patients Undergoing HSCT

Effectiveness of Extraoral Photobiomodulation Protocols in Management of Oral Adverse Effects in Patients Undergoing Hematopoietic Stem Cell Transplantation

The measurement of mucositis will be performed daily from the beginning of the conditioning therapy until the bone marrow grafting or while there are oral lesions.

Mucositis will be scored according to WHO criteria: grade 0 (none), grade I (oral soreness, erythema), grade II (oral erythema, ulcers, solid and liquid diet tolerated), grade III (oral ulcers, liquid diet only), and grade IV (oral diet impossible).

The measurement of mucositis will be performed daily from the beginning of the conditioning therapy until the bone marrow grafting or while there are oral lesions.

The National Cancer Institute (NCI) scale (NCI - Common Terminology Criteria for Adverse Events) will be performed: grade I (mucosal erythema), grade II ( patchy ulcerations with pseudomembranes), grade III (confluent ulceration or pseudomembranes, bleeding with minor trauma), and grade IV (tissue necrosis, significant spontaneous bleeding)

Evaluation of pain, will be employed the visual analogical scale (VAS). Pain evaluation will be performed daily from the beginning of the conditioning therapy until the bone marrow grafting or while there are oral lesions.

VAS scale will be represented by a 10 centimeters line, 0 corresponding no pain ranging up to 10 worst pain possible. The patient will be instructed to slide the marker though 10 centimeters line.

Also, Numeric Rating Scale (NRS-101) will be employed. Pain evaluation will be performed daily from the beginning of the conditioning therapy until the bone marrow grafting or while there are oral lesions.

NRS-101, the patients will be instructed to assign one number between 0 (no pain) varying until 100 (worst pain possible).

Analysis of chewing, swallowing, liquid intake and taste alteration. Responses will be scored daily ranging from 0 - no difficulty, to 4 - impossible to accomplish. The functional evaluation will be performed daily from the beginning of the conditioning therapy until the bone marrow grafting or while there are oral lesions.

Will be taken into account - total absence of dysphagia, dysphagia to solid food and dysphagia to any liquid or solid food. Dysfagia evaluation will be performed daily from the beginning of the conditioning therapy until the bone marrow grafting or while there are oral lesions.

* Non-stimulated saliva: the patient will be instructed to sit down calmly, tilt the head down, a millimeter collection tube, positioned below the lower lip, for 5 minutes, all the saliva produced will be deposited in the tube
* Stimulated saliva: the patient will remain seated, with the head tilted forward and the collection of non-stimulated saliva will be performed immediately afterwards. With the patient in the same position, he will chew a silicone sialogogue provided and all the saliva produced during the 5-minute period will be dispensed into another tube identical to the first one. The measurement of the volume of saliva collected will be considering the graduation of the tube.

Parameters: \< 0.1 ml/min will be considered hyposalivation for unstimulated, \< 0.7 ml/min for stimulated salivation

Saliva samples will be collected at the beginning of the conditioning, on the day of the HSCT and on the bone marrow marrow grafting day.

The Oral Health Impacts Profile questionnaire (OHIP -14) will be employed. Quality of life will be evaluated at the beginning of the conditioning, on the day of the HSCT and on the bone marrow marrow grafting day.

OHIP is a questionnaire that measures people's perception of the social impact of oral disorders on their well-being. Fourteen items of OHIP are divided into seven dimensions; functional limitation, physical discomfort, psychological discomfort, physical disability, psychological disability, social disability and handicaps.

The responses are rated on a 5-point Likert scale: 0 = never; 1 = hardly ever; 2 = occasionally; 3 = fairly often; 4 = very often/every day. The OHIP-14 scores can range from 0 to 56 and are calculated by summing the ordinal values for the 14 items. The domain scores can range from 0 to 8. Higher OHIP-14 scores indicate worse and lower scores indicate better quality of life.

The measure of the time application will be take with a timer during all photobiomodulation sessions

To assess the impact of treatment on oral health, the manual of epidemiological studies for oral health surveys proposed by the World Health Organization (WHO) will be used. The community periodontal index (CPI) will be used, evaluating two indicators of periodontal condition: gingival bleeding and periodontal pockets (adopting index teeth to record attachment loss).

An evaluation of the dental condition will also be carried out.

Oral health will be evaluated at the beginning of the conditioning, on the day of the HSCT, on the bone marrow marrow grafting day, one year and two years after bone marrow grafting.

Saliva samples will be collected through SWAB friction in buccal mucosa. After that, the SWABS will be emerged in a buffering saline solution. The tubes will be centrifuged for five minutes at 5000 rpm and the precipitates will be collected. Samples will be frozen in liquid nitrogen and immediately stored at -80 °C until the DNA extraction step.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia	NCT01420783	Hematopoietic N...	SAR302503	18 Years -	Sanofi
Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib	NCT01523171	Hematopoietic N...	SAR302503	18 Years -	Sanofi
Phase 2 Study of SAR302503 in Patients With Myelofibrosis	NCT01420770	Hematopoietic N...	SAR302503	18 Years -	Sanofi
GVHD Prophylaxis With Methotrexate in Haploidentical HCT Using Posttransplant Cyclophosphamide	NCT04622956	Graft Vs Host D... Hematopoietic N...	Methotrexate In...	18 Years - 70 Years	University of Sao Paulo General Hospital
Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis	NCT01437787	Hematopoietic N...	SAR302503 Placebo	18 Years -	Sanofi
Effectiveness of Extraoral Photobiomodulation in Management of Oral Adverse Effects in Patients Undergoing HSCT	NCT05759975	Oral Mucositis Hematopoietic N... Xerostomia Hyposalivation	Photobiomodulat... Photobiomodulat...	18 Years - 90 Years	Federal University of Rio Grande do Sul
Phase 2 Study of SAR302503 in Patients With Myelofibrosis	NCT01420770	Hematopoietic N...	SAR302503	18 Years -	Sanofi
Effectiveness of Extraoral Photobiomodulation in Management of Oral Adverse Effects in Patients Undergoing HSCT	NCT05759975	Oral Mucositis Hematopoietic N... Xerostomia Hyposalivation	Photobiomodulat... Photobiomodulat...	18 Years - 90 Years	Federal University of Rio Grande do Sul
Effectiveness of Extraoral Photobiomodulation in Management of Oral Adverse Effects in Patients Undergoing HSCT	NCT05759975	Oral Mucositis Hematopoietic N... Xerostomia Hyposalivation	Photobiomodulat... Photobiomodulat...	18 Years - 90 Years	Federal University of Rio Grande do Sul

Spots Global Cancer Trial Database for hematopoietic neoplasm