Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Behaviors and Mental Disorders

Nervous System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Leukemia

Mastocytosis

Aggression

Mastocytosis, Systemic

Leukemia, Mast-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Dementia

Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Mast Cell Activation Disorders

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Systemic Mastocytosis

Acute Graft Versus Host Disease

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Tyrosine Kinase Inhibitors

Midostaurin

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Midostaurin was administered at a dose of 100 mg twice daily (bid) in continuous cycles of 28 days until disease progression, intolerable toxicity or withdrawal due to any cause, whichever occurred first.

Midostaurin was provided as 25 mg soft gelatin capsules for oral administration.

Midostaurin (PKC412)

Novartis Pharmaceuticals

The purpose of this study was to determine the efficacy and safety of twice daily (bid) oral midostaurin in patients with Aggressive Systemic Mastocytosis (ASM) or Mast Cell Leukemia (MCL) with or without an Associated Hematological clonal Non-Mast cell lineage Disease (AHNMD).

Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia

A Single Arm, Phase II, Open-Label Study to Determine the Efficacy of 100mg Twice Daily Oral Dosing of Midostaurin Administered to Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia +/- an Associated Hematological Clonal Non-Mast Cell Lineage Disease

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Overall Response Rate (ORR) was defined as the percentage of participants who classified as confirmed responders (Major Response (MR) or Partial Response (PR)) by the adjudication of the SSC and based on a Modified Valent Criteria.

A major responder had complete resolution of at least one C-Finding and no progression in other C-Findings. A partial responder showed a measurable improvement in one or more C-Finding(s) without confirmed progression in other C-Findings. A C-Finding was a Clinical Finding, which was considered by the investigator and corroborated by the Study Steering Committee (SSC) Chairperson or designee, attributable to the mast cell disease component and not the associated hematological clonal non-mast cell lineage disease (AHNMD) component or any other cause.

The Duration of response (DoR) was defined as the time from first onset of confirmed response (MR or PR) to the date of first documented and confirmed progression or death due to ASM/MCL.

The Time to response (TTR) was defined as the time from start of treatment until the date of onset of confirmed response (MR or PR).

The Progression-free survival (PFS) is defined as the time from start of treatment to the date of the first documented and confirmed progression or death due to any cause.

The Overall Survival (OS) is defined as the time from start of treatment to the date of death due to any cause.

Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC)

Histopathologic response was summarized to demonstrate the change from baseline in percentage of mast cell infiltrations in the Bone Marrow (BM) and related serum tryptase levels.

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Age Continuous (PEP)

PEP (n=89) - Female

PEP (n=89) - Male

Sex: Female, Male (PEP)

PEP (n=89) - Black

PEP (n=89) - White

PEP (n=89) - Other/Missing

Race (PEP)

The Participant Flow was on the Full Analysis Set (FAS), the Baseline Characteristics were done on the FAS and Primary Efficacy Population (PEP). The Efficacy analysis was done on the PEP (except for the Overall Survival which was done on FAS and PEP). The Safety analysis was done on the Safety Set (SS).

Study Director

Primary Efficacy Population: participants assigned to study treatment who met diagnostic criteria for aggressive systemic mastocytosis or mast cell leukemia and presented with at least 1 measurable C-Finding at study entry and/or participants with transfusion dependent anemia due to their underlying disease at study entry as confirmed by the SCC.

Percentage of Participants With Overall Response Rate (ORR)

Primary Efficacy Population (PEP), which consisted of all participants with a confirmed response, was considered.

Median Time to Duration of Response (DoR)

Median Time to Response (TTR)

Median Time to Progression-Free Survival (PFS)

Primary Efficacy Population (PEP) (n=89)

Full Analysis Set (FAS) (n=116)

Primary Efficacy Population (PEP), which consisted of all participants with a confirmed response and the Full Analysis Set (FAS), which consisted of all patients who received at least one dose of study drug were considered.

Median Time to Overall Survival (OS)

AEs by Primary System Organ Class (SOC) (n=116)

SAEs by Primary System Organ Class (SOC) (n=88)

Deaths by Primary System Organ Class (SOC) (n=25)

Long-term Safety and Tolerability of Midostaurin

>50% decrease in mast cell (MC) (n=41)

>0-<=50% decrease in mast cell (MC) (n=19)

>50% decrease in serum tryptase (n=52)

>0-<=50% decrease in serum tryptase (n=25)

Primary Efficacy Population (PEP); for each patient, the best improvement relative to Baseline was considered.

Histopathologic Response

Overall Study

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Carboplatin

Dexamethasone

Etoposide

Rituximab

Ifosfamide

Dexamethasone acetate

Etoposide phosphate

Isophosphamide mustard

Antineoplastic Agents, Immunological

Immunologic Factors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Alkylating

Alkylating Agents

All subjects will receive KPT-330 (selinexor) on days -5 and -3 starting one week before RICE chemotherapy is started. Once chemotherapy starts, selinexor will be given on days 1, 3, and 5 of each chemotherapy cycle.

RICE chemotherapy will consist of Rituximab, ifosfamide, carboplatin, etoposide, and dexamethasone.

KPT-330 administered orally on days -5 and -3 prior to starting chemotherapy. Once chemotherapy starts, KPT-330 will be administered on days 1, 3, and 5 of each cycle. Dose levels will range from 20 mg to 100mg with a standard 3+3 escalation schema.

KPT-330

20 mg qd on Days -5 and -3. 20 mg qd on Days 1-5

Peter Martin, MD

This study evaluates the addition of selinexor (KPT-330) to RICE chemotherapy in the treatment of relapsed and refractory aggressive B-Cell Lymphoma, with the goal of improved response rates (as compared to RICE chemotherapy alone).

Although aggressive B-cell lymphomas are potentially curable with front-line chemotherapy, at least one-third of patients experience progression or relapse. Second-line regimens such as rituximab, ifosfamide, carboplatin, and etoposide (RICE) are administered with the goal of cytoreduction prior to autologous stem cell transplantation (ASCT) in eligible patients. However, half of patients who receive salvage treatment and ASCT are still not cured.

Selinexor is a Selective Inhibitor of Nuclear Export / SINE compound, which is a new class of molecule. SINE compounds have been shown to induce apoptotic cell death in pre-clinical models of AML, CLL, T-ALL, and Ph+ ALL as well as B and T-cell non-Hodgkin lymphomas. Preliminarily, selinexor has demonstrated promising single-agent clinical activity in patients with previously treated NHL including DLBCL, warranting further investigation. Based on promising preclinical and clinical data, selinexor is currently under evaluation in combination with chemotherapy for solid tumors.

The investigators hypothesize that the combination of selinexor plus RICE will be well-tolerated and clinically active in participants with previously treated aggressive B-cell lymphomas and propose a phase I trial to evaluate this combination. Moreover, Investigators will evaluate primary patient samples before and after selinexor to investigate the mechanisms of action of selinexor, including the mechanisms by which selinexor sensitizes cells to chemotherapy, and evaluate other novel drug combinations in aggressive B-cell lymphomas.

KPT-330 Plus RICE for Relapsed/Refractory Aggressive B-Cell Lymphoma

A Phase I Investigator-Initiated Study of Selinexor (KPT-330) Plus RICE in Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

The highest dose level at which no more than 1 or 6 patients presents with a dose-limiting toxicity (DLT) during the first 6 cycles of treatment

Overall survival of patients enrolled on KPT-330 + RICE

Progression-free survival of patients enrolled on KPT-330+RICE

The efficacy (as assessed by clinical response) of the combination of KPT-330 + RICE in patients with Rel/Ref b-cell lymphoma

The number of patients who can feasibly undergo a stem cell transplant after treatment with KPT-330+RICE

Karyopharm Therapeutics Inc

The Leukemia and Lymphoma Society

FDA Office of Orphan Products Development

Weill Medical College of Cornell University

Clofarabine

Antimetabolites

Clofarabine 30 mg/m2/day will be administered as a 2-hour intravenous infusion (IVI) on days 1-5.

Kristie Blum

This study will determine the efficacy of clofarabine as measured by response rate in patients with aggressive non-Hodgkin's lymphoma

Rationale: Two Food and Drug Administration drugs approved for blood cancers such as non-Hodgkin's lymphoma (NHL) include fludarabine (Fludara) and cladribine (Leustat). The drug offered in the current study, clofarabine was designed to combine the anti-cancer strength of both fludarabine and cladribine. Laboratory research suggests that clofarabine targets anti-cancer mechanisms in cells, helps repair DNA, and inhibits tumor growth. Research also indicates that clofarabine has some efficacy against a variety of blood cancers and solid tumors. Numerous tumor responses have been observed with high doses of clofarabine in heavily pretreated patients with different types of lymphoma. The current study build on this previous research to test clofarabine in patients with aggressive NHL.

Purpose: This study will evaluate the safety and efficacy of clofarabine for aggressive NHL. Toxicities resulting from the combination of clofarabine and the supportive care drug GM-CSF will also be analyzed in patients. GM-CSF is a blood-forming agent that stimulates the production of white blood cells. In addition, several tests, including blood and tumor tissue analysis, will assess immune response and biological changes to the tumor as a result of study drugs.

Treatment: Patients in this study will be given clofarabine through intravenous infusions. This drug will initially be provided to patients for five consecutive days. Several tests will then be conducted and supportive care agents will be administered to stabilize patients' blood cell counts, immune response, and reduce the risk of infection. The first ten patients in this study will be hospitalized until recovery from the first five days of clofarabine to carefully monitor any additional toxicities resulting from the dosing regimen. Patients will receive another five day treatment cycle with clofarabine within seven days after recovering from each previous cycle and no more than four weeks from the start of the previous cycle. Disease response will be measured after every two cycles of treatment with clofarabine. Patient with stable or reduced disease will receive a maximum of six treatment cycles with clofarabine. Treatments will be discontinued due to disease growth, unacceptable side effects, or a treatment delay of more than 21 days.

A Phase II Study of Clofarabine in Patients With Aggressive Non-Hodgkin's Lymphoma

Ohio State University Comprehensive Cancer Center

Gland and Hormone Related Diseases

Thyroid Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Cancer, Papillary

Neoplasms, Glandular and Epithelial

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Adenocarcinoma

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

This mutation will be analysed using the tumor tissues of the patients operated for thyroid diseases and diagnosed with papillary thyroid carcinoma. And mutation positive patients will be investigated for the aggressive characteristics of the tumor.

BRAF V600E mutation analysis will be made using the tumor tissues of the patients with papillary thyroid cancer (3 sections of 7 mm from he paraffin blocks). And mutation positives and negatives will be identified.

BRAF V600E POSITIVITY

Yeliz E Ersoy, DR

Yeliz E Ersoy, M.D.

The purpose of this study is to determine whether BRAF V600E mutation in our patients with papillary thyroid cancer has an association with poor prognosis.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy and BRAF V600E mutation is the most common genetic alteration identified in PTC, ranging from 25 to 80%, with the average rate about 45%. Various studies demonstrated a relationship between BRAF V600E mutation and aggressive characteristics of the cancer, including the worse patient prognosis. But,there are no studies from Turkey regarding this topic. So the investigators will examine BRAF V600E mutation in our patients with PTC and try to assess the role of this mutation in prognosis and further management of the patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia	NCT00782067	Leukemia	Midostaurin (PK...	18 Years -	Novartis
KPT-330 Plus RICE for Relapsed/Refractory Aggressive B-Cell Lymphoma	NCT02471911	Diffuse Large B...	KPT-330 Rituximab Etoposide Carboplatin Ifosfamide Dexamethasone	18 Years -	Weill Medical College of Cornell University
A Phase II Study of Clofarabine in Patients With Aggressive Non-Hodgkin's Lymphoma	NCT00201669	Non-Hodgkin's L...	Clofarabine	18 Years -	Ohio State University Comprehensive Cancer Center
BRAF V600E Mutations In Papillary Thyroid Carcinoma	NCT01417442	Papillary Thyro...	BRAF V600E POSI...	-	Bezmialem Vakif University
BRAF V600E Mutations In Papillary Thyroid Carcinoma	NCT01417442	Papillary Thyro...	BRAF V600E POSI...	-	Bezmialem Vakif University
KPT-330 Plus RICE for Relapsed/Refractory Aggressive B-Cell Lymphoma	NCT02471911	Diffuse Large B...	KPT-330 Rituximab Etoposide Carboplatin Ifosfamide Dexamethasone	18 Years -	Weill Medical College of Cornell University

Spots Global Cancer Trial Database for aggressive

Every month we try and update this database with for aggressive 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 aggressive

Every month we try and update this database with for aggressive 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 aggressive 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.