There are 17 clinical trials

Clinical Trials

1 Efficacy of Tyrosine Kinase Inhibition in Reducing Eosinophilia in Patients With Myeloid and/or Steroid-Refractory Hypereosinophilic Syndrome

The purpose of this study is to evaluate the safety and efficacy of the tyrosine kinase inhibitor, imatinib mesylate (Gleevec ) in reducing peripheral blood eosinophilia in patients with the myeloid form of hypereosinophilic syndrome (HES). Patients with the hypereosinophilic syndrome who meet a set of criteria designed to select patients with the myeloid form of the disease, as well as patients without myeloid disease who are refractory to standard therapy for HES, will be admitted on this protocol. A thorough clinical evaluation will be performed with emphasis on potential sequelae of eosinophil-mediated tissue damage. A baseline bone marrow will be obtained to exclude leukemia or lymphoma and to assess the degree and nature of eosinophilopoiesis. Bone marrow, blood cells and/or serum will also be collected to test for the presence of a recently described mutation that is associated with imatinib-responsiveness in HES, and to provide reagents (such as DNA, RNA, and specific antibodies) and for use in the laboratory to address issues related to the mechanism of action of imatinib mesylate in HES. Imatinib mesylate will be initiated at a dose of 400 mg daily, the FDA-approved dose for the treatment of chronic myelogenous leukemia. In patients who demonstrate a complete clinical and hematologic response to imatinib therapy and who do not have life-threatening disease, the dose will be decreased gradually to 100mg daily and then discontinued. In order to minimize bone marrow suppression, other myelosuppressive agents will be tapered and discontinued during the first week of therapy with imatinib mesylate. Complete blood counts will be performed weekly for the first month and biweekly thereafter. Clinical assessments will be performed every three months to assess progression of end organ damage. In patients who demonstrate a complete clinical and hematologic response to imatinib therapy and who do not have life-threatening disease, the dose will be decreased gradually to 100 mg daily and then discontinued. In the event of clinical, hematologic or molecular relapse during the taper, the imatinib dose will be increased to a maximum of 600 mg daily to achieve a second remission. Laboratory monitoring will be performed as above except for molecular monitoring which will be monitored monthly if drug is discontinued or molecular relapse occurs. Once a stable dosing regimen is achieved for greater than or equal to 6 months in subjects who have undergone dose descalation or greater than or equal to 2 years in subjects receiving 300-400 mg of imatinib daily who did not qualify for dose de-escalation, the frequency of NIH visits and end organ assessments will be decreased to 6 months, with molecular monitoring every 3 months and monthly routine laboratory assessments.

NCT00044304 Eosinophilic Myeloid Neoplasm Hypereosinophilic Syndrome Drug: Imatinib Drug: Ruxolitinib

MeSH:Hypereosinophilic Syndrome Syndrome

EXCLUSION CRITERIA: 1. Pregnancy or nursing women 2. HIV positivity or other known immunodeficiency 3. D816V KIT-positive systemic mastocytosis 4. Absolute neutrophil count less than 1000/mm(3) or platelet count less than 10,000/mm(3) or less than 50,000/m(3) with clinical evidence of bleeding. --- D816V ---

2 Imatinib Mesylate in Patients With Various Types of Malignancies Involving Activated Tyrosine Kinase Enzymes

This trial is for various types of malignancies which may depend on certain enzymes (tyrosine kinases) for growth. The objective of this study is to assess to what extent imatinib mesylate blocks these enzymes and to assess the effect on the malignancy.

NCT00171912 Hypereosinophilic Syndrome Systemic Mastocytosis Chronic Myelomonocytic Leukemia Dermatofibrosarcoma Drug: imatinib mesylate

MeSH:Leukemia Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Mastocytosis Mastocytosis, Systemic Dermatofibrosarcoma Hypereosinophilic Syndrome Neoplasms

HPO:Chronic myelomonocytic leukemia Juvenile myelomonocytic leukemia Leukemia Mastocytosis Neoplasm

Exclusion Criteria: 1. Certain leukaemias (abl-mutated), some gastrointestinal stromal tumours (c-KIT-positive) or certain systemic mastocytosis (if c- KIT D816V mutation). --- D816V ---

Not included: Patients with chronic myeloid leukemia, some other types of leukemias (abl-mutated) some types of gastrointestinal stromal tumours (c-KIT-positive), some systemic mastocytosis (if c-KIT D816V mutation), brain, prostate, breast or lung cancers. --- D816V ---

3 Investigation of Cellular and Molecular Pathologic Mechanisms in Mast Cell Disorders.

Mastocytosis is a disorder characterized by presence of excessive numbers of mast cells in skin, bone marrow and internal organs. It can affect both children and adults, males and females and individuals from all ethnic backgrounds, although precise demographic information about the affected populations is not available as it is a rare disorder. Mastocytosis in children is generally limited to the skin and follows a self limited course, while it is a disorder of the hematopoietic stem cell associated with somatic mutations of the c-kit gene in most patients with adult-onset of disease. There is no known curative therapy for most patients with systemic mastocytosis. Recent research studies identified several subtypes of disease with distinct clinical and pathologic features, however, a precise understanding of the incidence as well as molecular pathology of different disease subtypes is lacking. This study aims to examine molecular and cellular pathological aspects of disease in patients with mastocytosis and correlate findings with clinical presentation and prognosis. Patients will undergo a routine history and physical examination, and diagnostic tests will be ordered as dictated by each patient's clinical presentation. Blood and bone marrow will be obtained for diagnostic and research purposes. Genetic analysis of the c-kit gene regulating mast cell growth and differentiation will be performed. It is hoped that findings obtained from this study will help to design novel therapies for mastocytosis and other disorders in which mast cells play a critical role.

NCT00336076 Mastocytosis Other: Collection of blood and bone marrow

MeSH:Mastocytosis

HPO:Mastocytosis

Proportion of KIT D816V mutation in blood, bone marrow and sorted mast cells. --- D816V ---

KIT D816V mutation was assessed in patient samples containing various proportions of neoplastic mast cells.. Inclusion Criteria: - Confirmed or suspected diagnosis of mastocytosis. --- D816V ---

4 Phase II Study of Thalidomide in Mastocytosis

RATIONALE: Thalidomide may stop the growth of systemic mastocytosis by blocking blood flow to the disease. PURPOSE: This phase II trial is studying how well thalidomide works in treating patients with relapsed or progressive systemic mastocytosis.

NCT00769587 Non Neoplastic Condition Precancerous Condition Drug: thalidomide

MeSH:Mastocytosis Precancerous Conditions Mastocytosis, Systemic Disease

HPO:Mastocytosis

DISEASE CHARACTERISTICS: - Diagnosis of systemic mastocytosis - Aggressive or borderline (smoldering) disease (in first line or more) - Relapsed or progressive disease - Measurable or evaluable disease - Presence of c-Kit D816V mutation in the skin, spine, or infiltrated organs - No nonsymptomatic mastocytosis PATIENT CHARACTERISTICS: - Life expectancy > 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for 1 month prior to, during, and until first menstrual cycle after completion of study treatment - Bilirubin < 2 times normal (unrelated to disease) - Liver enzymes < 2 times normal (unrelated to disease) - Creatinine ≤ 300 mmol/L - No central or peripheral neuropathy leading to psychiatric concerns - No HIV positivity - No active infection or other serious underlying illness that would preclude treatment - No history of thromboembolism or deep vein thrombosis - No geographical, social, or psychological reasons preventing medical monitoring PRIOR CONCURRENT THERAPY: - More than 4 weeks since prior antitumor therapy (e.g., chemotherapy, radiotherapy) - No other concurrent treatment specific for this disease - No concurrent participation in another experimental drug trial DISEASE CHARACTERISTICS: - Diagnosis of systemic mastocytosis - Aggressive or borderline (smoldering) disease (in first line or more) - Relapsed or progressive disease - Measurable or evaluable disease - Presence of c-Kit D816V mutation in the skin, spine, or infiltrated organs - No nonsymptomatic mastocytosis PATIENT CHARACTERISTICS: - Life expectancy > 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for 1 month prior to, during, and until first menstrual cycle after completion of study treatment - Bilirubin < 2 times normal (unrelated to disease) - Liver enzymes < 2 times normal (unrelated to disease) - Creatinine ≤ 300 mmol/L - No central or peripheral neuropathy leading to psychiatric concerns - No HIV positivity - No active infection or other serious underlying illness that would preclude treatment - No history of thromboembolism or deep vein thrombosis - No geographical, social, or psychological reasons preventing medical monitoring PRIOR CONCURRENT THERAPY: - More than 4 weeks since prior antitumor therapy (e.g., chemotherapy, radiotherapy) - No other concurrent treatment specific for this disease - No concurrent participation in another experimental drug trial Non Neoplastic Condition Precancerous Condition Mastocytosis Precancerous Conditions Mastocytosis, Systemic Disease OBJECTIVES: Primary - Determine the objective response rate at 6 months in patients with systemic mastocytosis treated with thalidomide. --- D816V ---

DISEASE CHARACTERISTICS: - Diagnosis of systemic mastocytosis - Aggressive or borderline (smoldering) disease (in first line or more) - Relapsed or progressive disease - Measurable or evaluable disease - Presence of c-Kit D816V mutation in the skin, spine, or infiltrated organs - No nonsymptomatic mastocytosis PATIENT CHARACTERISTICS: - Life expectancy > 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for 1 month prior to, during, and until first menstrual cycle after completion of study treatment - Bilirubin < 2 times normal (unrelated to disease) - Liver enzymes < 2 times normal (unrelated to disease) - Creatinine ≤ 300 mmol/L - No central or peripheral neuropathy leading to psychiatric concerns - No HIV positivity - No active infection or other serious underlying illness that would preclude treatment - No history of thromboembolism or deep vein thrombosis - No geographical, social, or psychological reasons preventing medical monitoring PRIOR CONCURRENT THERAPY: - More than 4 weeks since prior antitumor therapy (e.g., chemotherapy, radiotherapy) - No other concurrent treatment specific for this disease - No concurrent participation in another experimental drug trial DISEASE CHARACTERISTICS: - Diagnosis of systemic mastocytosis - Aggressive or borderline (smoldering) disease (in first line or more) - Relapsed or progressive disease - Measurable or evaluable disease - Presence of c-Kit D816V mutation in the skin, spine, or infiltrated organs - No nonsymptomatic mastocytosis PATIENT CHARACTERISTICS: - Life expectancy > 3 months - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for 1 month prior to, during, and until first menstrual cycle after completion of study treatment - Bilirubin < 2 times normal (unrelated to disease) - Liver enzymes < 2 times normal (unrelated to disease) - Creatinine ≤ 300 mmol/L - No central or peripheral neuropathy leading to psychiatric concerns - No HIV positivity - No active infection or other serious underlying illness that would preclude treatment - No history of thromboembolism or deep vein thrombosis - No geographical, social, or psychological reasons preventing medical monitoring PRIOR CONCURRENT THERAPY: - More than 4 weeks since prior antitumor therapy (e.g., chemotherapy, radiotherapy) - No other concurrent treatment specific for this disease - No concurrent participation in another experimental drug trial Non Neoplastic Condition Precancerous Condition Mastocytosis Precancerous Conditions Mastocytosis, Systemic Disease OBJECTIVES: Primary - Determine the objective response rate at 6 months in patients with systemic mastocytosis treated with thalidomide. --- D816V --- --- D816V ---

5 Randomized, Placebo-controlled, Phase 3 Study to Compare Efficacy and Safety of Masitinib at 6 mg/kg/Day to Placebo in Treatment of Patients With Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis With Handicap

The objective of this study is to compare the safety and efficacy of masitinib (AB1010) to placebo in patients with mastocytosis with handicap.

NCT00814073 Indolent Systemic Mastocytosis Drug: Masitinib Drug: Placebo Other: Best Supportive Care

MeSH:Mastocytosis Mastocytosis, Systemic

HPO:Mastocytosis

The objective of this phase 3 study was therefore to evaluate masitinib efficacy and safety in severe systemic mastocytosis patients, with or without D816V mutation of c-Kit. --- D816V ---

6 Phase IIa, Open-label, Randomized Study of Oral AB1010 in Patients With Systemic Indolent Mastocytosis With Handicap and Not Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V)

This is a 12 weeks study aimed at assessing the safety and efficacy of 2 doses of AB1010 in patients suffering from indolent systemic mastocytosis with handicap.

NCT00831974 Mastocytosis Drug: masitinib (AB1010) Drug: masitinib (AB1010)

MeSH:Mastocytosis

HPO:Mastocytosis

Phase IIa, Open-label, Randomized Study of Oral AB1010 in Patients With Systemic Indolent Mastocytosis With Handicap and Not Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V). --- Asp-816-Val ---

Phase IIa, Open-label, Randomized Study of Oral AB1010 in Patients With Systemic Indolent Mastocytosis With Handicap and Not Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V). --- Asp-816-Val --- --- D816V ---

3. The absence of an activating point mutation in the phosphotransferase domain of c-Kit such as D816V c-Kit mutation in at least one of the two infiltrated organs: bone marrow and/or skin and/or other tissue. --- D816V ---

7 A 12-week With Possible Extension, Prospective, Multicenter, Randomized, Open-label, 2-parallel Group, Phase IIa Study to Compare Efficacy and Safety of AB1010 at 3 or 6 mg/kg/Day in Treatment of Patients With Mastocytosis With Handicap and Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V)

The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V).

NCT01266369 Mastocytosis Drug: masitinib

MeSH:Mastocytosis

HPO:Mastocytosis

A 12-week With Possible Extension, Prospective, Multicenter, Randomized, Open-label, 2-parallel Group, Phase IIa Study to Compare Efficacy and Safety of AB1010 at 3 or 6 mg/kg/Day in Treatment of Patients With Mastocytosis With Handicap and Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V). --- Asp-816-Val ---

A 12-week With Possible Extension, Prospective, Multicenter, Randomized, Open-label, 2-parallel Group, Phase IIa Study to Compare Efficacy and Safety of AB1010 at 3 or 6 mg/kg/Day in Treatment of Patients With Mastocytosis With Handicap and Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V). --- Asp-816-Val --- --- D816V ---

Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V). --- D816V ---

Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V). --- D816V --- --- Asp-816-Val ---

Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V). --- D816V --- --- Asp-816-Val --- --- D816V ---

Pruritus score at week 12 Number of flushes per week at week 12 Hamilton score at week 12 Fatigue Impact scale at week 12. Inclusion Criteria: 1. Patients with one of the following documented mastocytosis: - Smouldering systemic mastocytosis - Indolent systemic mastocytosis with organomegaly - Indolent Systemic Mastocytosis having 2 infiltrated organs (skin and bone-marrow) - Any mastocytosis with in the last 6 months at least 3 anaphylactic shocks or syncops requiring either use of adrenaline or medical assistance - Cutaneous Mastocytosis (CM) 2. Skin biopsy-documented mastocytosis and evaluable disease based upon: - Histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin biopsy - Clinical criteria: typical skin lesions (maculopapular, urticaria pigmentosa, mastocytoma) 3. Missing data (c-kit molecular analysis not done) or documented presence of an activating point mutation in the phosphotransferase domain of c-kit such as D816V c-kit mutation in at least one infiltrated organ (bone marrow or skin) 4. Refractory to at least one of the symptomatic treatments such as: - Anti H1 - Anti H2 - Proton pump inhibitor - Osteoclast inhibitor - Cromoglycate Sodium - Antileukotriene - Other therapies used for the symptomatic care 5. Handicap defined as at least one of the following handicaps: - pruritus score ≥ 6 - number of flushes per week ≥ 7 - number of stools per day ≥ 4 , - number of mictions per day ≥ 8 , - QLQ-C30 score ≥ 60, - Hamilton score ≥ 10 Exclusion Criteria: 1. Patients with one of the following mastocytosis: - Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD) - Mast cell leukemia (MCL) - Aggressive systemic mastocytosis (ASM) 2. Patient with a major surgery within 2 weeks prior to study entry 3. --- D816V ---

- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection Inclusion Criteria: 1. Patients with one of the following documented mastocytosis: - Smouldering systemic mastocytosis - Indolent systemic mastocytosis with organomegaly - Indolent Systemic Mastocytosis having 2 infiltrated organs (skin and bone-marrow) - Any mastocytosis with in the last 6 months at least 3 anaphylactic shocks or syncops requiring either use of adrenaline or medical assistance - Cutaneous Mastocytosis (CM) 2. Skin biopsy-documented mastocytosis and evaluable disease based upon: - Histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin biopsy - Clinical criteria: typical skin lesions (maculopapular, urticaria pigmentosa, mastocytoma) 3. Missing data (c-kit molecular analysis not done) or documented presence of an activating point mutation in the phosphotransferase domain of c-kit such as D816V c-kit mutation in at least one infiltrated organ (bone marrow or skin) 4. Refractory to at least one of the symptomatic treatments such as: - Anti H1 - Anti H2 - Proton pump inhibitor - Osteoclast inhibitor - Cromoglycate Sodium - Antileukotriene - Other therapies used for the symptomatic care 5. Handicap defined as at least one of the following handicaps: - pruritus score ≥ 6 - number of flushes per week ≥ 7 - number of stools per day ≥ 4 , - number of mictions per day ≥ 8 , - QLQ-C30 score ≥ 60, - Hamilton score ≥ 10 Exclusion Criteria: 1. Patients with one of the following mastocytosis: - Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD) - Mast cell leukemia (MCL) - Aggressive systemic mastocytosis (ASM) 2. Patient with a major surgery within 2 weeks prior to study entry 3. --- D816V ---

8 Imatinib Mesylate Therapy in Systemic Mastocytosis Patients Lacking KIT Mutations

The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Imatinib Mesylate therapy in patients with systemic mastocytosis lacking KIT mutations.

NCT01297777 Systemic Mastocytosis Drug: Imatinib Mesylate

MeSH:Mastocytosis Mastocytosis, Systemic

HPO:Mastocytosis

Systemic Mastocytosis Mastocytosis Mastocytosis, Systemic In vitro studies have proven that imatinib inhibits wild type Kit (wtKit) and suppresses proliferation of the HMC-1V560G cell line, while it is ineffective on inhibiting the growth of HMC-1V560G, D816V cells. --- D816V ---

In contrast, several experiments have provided compelling evidence regarding the resistance against the growth-inhibitory effects of imatinib on cells carrying the D816V KIT mutation. --- D816V ---

9 Detection of Clonal Mast Cell Disorders Among Patients With Exercise-induced Anaphylaxis

Anaphylaxis is a serious allergic reaction that develops rapidly and can cause death. Some patients experience anaphylaxis is association with exercise, a disorder called exercise-induced anaphylaxis. A subset of patients with unexplained anaphylaxis, especially those with hypotension during the anaphylactic episodes, have been shown to have abnormal, clonal populations of a certain cell type, mast cells, in the bone marrow. This has been described in at least one patient with exercise-induced anaphylaxis. The investigators would like review the findings in a group of patients with exercise-induced anaphylaxis who have undergone evaluation for the presence of abnormal, clonal mast cells.

NCT01326741 Anaphylaxis

MeSH:Anaphylaxis Shock

HPO:Anaphylactic shock

Presence of clonal mast cells in bone marrow as assessed by D816V c-kit mutation or CD25 will be recorded for each participant.. Number of participants with presence of clonal abnormalities in the bone marrow specimen. --- D816V ---

Presence of clonal mast cells in bone marrow as assessed by D816V c-kit mutation or CD25 will be recorded for each participant. --- D816V ---

10 Subcutaneous Cladribine Plus Pegylated Interpheron Alfa-2a in Advanced Systemic Mastocytosis With D816V and Other Exon 17 KIT Mutations.

The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Cladribine plus Pegylated Interpheron alpha-2a therapy in patients with advanced systemic mastocytosis carrying D816V or other exon 17 KIT mutations.

NCT01602939 Systemic Mastocytosis Drug: Cladribine and pegylated interpheron alpha-2a

MeSH:Mastocytosis Mastocytosis, Systemic

HPO:Mastocytosis

Subcutaneous Cladribine Plus Pegylated Interpheron Alfa-2a in Advanced Systemic Mastocytosis With D816V and Other Exon 17 KIT Mutations.. Cladribine Plus Pegylated Interpheron Alfa-2a in Systemic Mastocytosis The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Cladribine plus Pegylated Interpheron alpha-2a therapy in patients with advanced systemic mastocytosis carrying D816V or other exon 17 KIT mutations. --- D816V ---

Subcutaneous Cladribine Plus Pegylated Interpheron Alfa-2a in Advanced Systemic Mastocytosis With D816V and Other Exon 17 KIT Mutations.. Cladribine Plus Pegylated Interpheron Alfa-2a in Systemic Mastocytosis The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Cladribine plus Pegylated Interpheron alpha-2a therapy in patients with advanced systemic mastocytosis carrying D816V or other exon 17 KIT mutations. --- D816V --- --- D816V ---

- Diagnosis of advanced systemic mastocytosis (aggressive systemic mastocytosis or proggressing systemic mastocytosis) with D816V or other exon 17 KIT mutations. --- D816V ---

11 Phase II Single Arm Open Pilot Study to Demonstrate the Efficacy of Midostaurin in Symptom Improvement and Decrease of Mast Cell Burden in Patients With Indolent or Smoldering Systemic Mastocytosis.

Rationale: Patients with indolent or smoldering systemic mastocytosis can have severe disabling symptoms. Almost all patients have fatigue, a compromised quality of life, hampering normal functioning. Because this form of mastocytosis is not considered life-threatening, mast cell eradication has never been applied and patients receive only symptomatic therapy with histamine blockers. Midostaurin, a c-KIT inhibitor has shown activity regarding symptom control and decrease of malignant mast cells in patients with aggressive systemic mastocytosis (ASM) or mast cell leukemia

NCT01920204 Indolent Systemic Mastocytosis Drug: Midostaurin,

MeSH:Mastocytosis Mastocytosis, Systemic

HPO:Mastocytosis

Number and grading of Common Terminology Criteria adverse events during the 6 months of therapy.. Inclusion Criteria: - Patients with Indolent Systemic Mastocytosis (ISM) or Smouldering Systemic Mastocytosis (SSM) according to the WHO criteria - Presence of the D816V c-KIT mutation - Serum tryptase > 20 mg/l - Serious mediator-related symptoms that cannot be controlled by H1 and H2 blocking drugs. --- D816V ---

- Any known other present malignancy, non-melanoma skin cancers excluded - History of malignancy within the last 5 years, non-melanoma skin cancers excluded - Any serious comorbidity interfering with therapy compliance and follow-up compliance - Pregnancy - Patients not willing or who are not able to comply with contraceptive measures Inclusion Criteria: - Patients with Indolent Systemic Mastocytosis (ISM) or Smouldering Systemic Mastocytosis (SSM) according to the WHO criteria - Presence of the D816V c-KIT mutation - Serum tryptase > 20 mg/l - Serious mediator-related symptoms that cannot be controlled by H1 and H2 blocking drugs. --- D816V ---

12 Phase II Study of Ponatinib for Advanced Cancers With Genomic Alterations in Fibroblastic Growth Factor Receptor (FGFR) and Other Genomic Targets (KIT, PDGFRá, RET FLT3, ABL1)

This phase II trial studies how well ponatinib hydrochloride works in treating patients with cancer that has spread to other parts of the body (metastatic), has failed previous treatment (refractory), and has one of several alterations, or mutations, in its deoxyribonucleic acid (DNA) sequence. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether a patient's genetic alterations may affect how well ponatinib hydrochloride works.

NCT02272998 Malignant Neoplasm Drug: ponatinib hydrochloride Other: laboratory biomarker analysis

MeSH:Neoplasms

HPO:Neoplasm

- Patients with known ponatinib-resistant gene alterations - PDGFRA D842V mutation - cKIT D816V mutation - FLT3 D835V/Y/H/F or Y842C mutations - FGFR3 K652E mutation - Major surgery (e.g. --- D842V --- --- D816V ---

13 A Phase 1 Study of BLU-285 in Patients With Advanced Systemic Mastocytosis (AdvSM) and Relapsed or Refractory Myeloid Malignancies

This is a Phase 1, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (also known as BLU-285), administered orally (PO), in adult patients with advanced systemic mastocytosis and other relapsed or refractory myeloid malignancies. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).

NCT02561988 Aggressive Systemic Mastocytosis Systemic Mastocytosis-associated Hematologic Non-mast Cell Disease Mast Cell Leukemia Relapsed or Refractory Myeloid Malignancies Drug: Avapritinib

MeSH:Mastocytosis Mastocytosis, Systemic Leukemia, Mast-Cell Neoplasms

HPO:Mastocytosis Neoplasm

Changes in levels of serum tryptase and levels of V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) D816V allele burden in blood. --- D816V ---

14 A Multicenter Phase 1, Open-Label Study of DCC-2618 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Malignancies

This is a Phase 1, open-label, first-in-human (FIH) dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity of DCC-2618, administered orally (PO), in adult patients with advanced malignancies. The study consists of 2 parts, a dose-escalation phase and an expansion phase.

NCT02571036 Gastrointestinal Stromal Tumors Advanced Systemic Mastocytosis Advanced Cancers Drug: DCC-2618 Drug: DCC-2618

MeSH:Gastrointestinal Stromal Tumors Mastocytosis Mastocytosis, Systemic

HPO:Gastrointestinal stroma tumor Mastocytosis

Patients with de novo imatinib resistant mutations, such as but not limited to KIT D816V or PDGFRA D842V, are eligible without prior imatinib therapy. --- D816V ---

15 An Open-label, Single Arm, Phase 2 Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis

This is an open-label, single arm, Phase 2 study evaluating the efficacy and safety of avapritinib (BLU-285) in patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL)

NCT03580655 Advanced Systemic Mastocytosis Aggressive Systemic Mastocytosis Systemic Mastocytosis With an Associated Hematologic Neoplasm Mast Cell Leukemia Drug: Avapritinib

MeSH:Mastocytosis Mastocytosis, Systemic Hematologic Neoplasms Leukemia, Mast-Cell

HPO:Hematological neoplasm Leukemia Mastocytosis

Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) mutation burden. --- D816V ---

16 A 3-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib (BLU-285), a Selective KIT Mutation-Targeted Tyrosine Kinase Inhibitor, in Indolent and Smoldering Systemic Mastocytosis With Symptoms Inadequately Controlled With Standard Therapy

This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. The study will be conducted in 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.

NCT03731260 Indolent Systemic Mastocytosis Drug: Avapritinib Drug: Placebo

MeSH:Mastocytosis Mastocytosis, Systemic

HPO:Mastocytosis

Part 2: Proportion of patients with a ≥50% reduction in peripheral blood V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele fraction or undetectable for patients with detectable mutation at Baseline. --- D816V ---

Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele burden in blood. --- D816V ---

17 A Phase 2 Randomized Double-Blinded Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutaneous Sarilumab in Improving the Quality of Life in Subjects With Indolent Systemic Mastocytosis

Background: Mast cells help the body fight disease and heal wounds. People with indolent systemic mastocytosis (ISM) make too many mast cells. This causes pain, tiredness, digestive problems, and other symptoms. Researchers think the drug sarilumab could help. Objective: To see if sarilumab is a safe and effective treatment for people with ISM. Eligibility: Adults ages 18-75 with ISM who are enrolled in NIH study 02-I-0277 Design: Participants will be screened with: - Physical exam - Medical history - Blood and urine tests - Questionnaires - Bone marrow removed by a needle inserted into the hip bone - Ultrasound of the abdomen - Photographs of the skin Participants will repeat some screening tests at study visits. Participants will have a baseline visit in the hospital for 3 days. They will: - Be assigned to get either the study drug or a placebo. They will not know which one they get. - Have a skin punch biopsy: An instrument will remove a small piece of skin. - Get their first drug dose injected under their skin Participants will keep a side effect and medication diary during the study. Participants will visit the clinic to get a drug dose every 2 weeks, for a total of 8 doses. Participants will have a visit 2 weeks after their final dose. It will last up to 2 days. Participants will have another visit 12 weeks later. Participants may then continue this study for 1 more year. Those who continue will get sarilumab, even if they previously got the placebo, every 2 weeks. They will have visits every 6 weeks, and then every 3 months.

NCT03770273 Indolent Systemic Mastocytosis Biological: Sarilumab Other: Placebo

MeSH:Mastocytosis Mastocytosis, System Mastocytosis, Systemic

HPO:Mastocytosis

Mastocytosis Quality of Life Questionnaire (MC-QoL).. QoL at 16 weeks post-initiation of study drug/placebo using the Mastocytosis Quality of Life Questionnaire (MC-QoL).. mast cells in bone marrow and allelic frequency of D816V. --- D816V ---

Decrease in the allelic frequency of D816V using PCR. --- D816V ---

HPO Nodes