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

Digestive System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Wounds and Injuries

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Stomach Neoplasms

Sarcoma

Gastrointestinal Stromal Tumors

Hematoma, Subdural

Sarcoma, Endometrial Stromal

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Endometrial Stromal Tumors

Endometrial Neoplasms

Uterine Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Stomach Cancer

Soft Tissue Sarcoma

Endometrial Stromal Sarcoma

Patients with histologically confirmed or clinical presentation suspicious of GIST

Audra A Satterwhite, R.N.

Andrew M Blakely, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Objective:

To follow people with GISTs and collect tumor tissue so that it can be studied in the lab.

Eligibility:

People age 6 and older who have a GIST.

Design:

Participants will be screened with a review of their medical records and samples.

Participants will enroll in 1 other NIH study, and may be asked to enroll in 2 other optional NIH studies.

Participants will have a medical history and physical exam. Data about how they function in their daily activities will be obtained.

Participants may speak with a genetic counselor. They may have genetic testing.

Participants will give blood samples. They may have a cheek swab. For this, small brush will be rubbed against the inside of the cheek.

Participants may have a computed tomography (CT) scan of the chest, abdomen, and pelvis. Or they may have a CT scan of the chest and magnetic resonance imaging (MRI) of the abdomen and pelvis.

Participants will be monitored every 6-12 months at the NIH Clinical Center, for up to 10 years before having surgery. If they need surgery, it will be performed at the NIH. Then, they will be monitored every 6-12 months, for up to 5 years after surgery.

If a participant has surgery, tumor tissue samples will be taken.

If a participant does not need surgery, their participation will end after 10 years. If they have surgery, the 5-year monitoring period will restart after each surgery.

Background:

Gastrointestinal stromal tumors (GISTs) are the most common gastrointestinal soft tissue sarcoma, but remain a rare disease entity.

Most GISTs are characterized by KIT or PDGFRA mutations, making them susceptible to tyrosine kinase inhibitor (TKI) therapy.

Wild-type (WT) GISTs are rarer tumors, usually characterized by SDH mutations and/or lack of KIT or PDGFRA mutations; paragangliomas are frequently associated with WT GISTs.

Non-WT GISTs may become refractory to TKI therapy, whereas WT GISTs are generally resistant to TKI therapy.

The primary treatment modality for GISTs is surgical resection, which may involve the stomach, liver, and/or peritoneal surfaces; most patients will require multiple operations to remove disease not responsive to systemic agents.

Investigational systemic therapies are limited by toxicity and/or lack of efficacy, resulting in an unmet need for novel treatment options.

Obtaining fresh tumor tissue is critical to the successful development of GIST models for drug research, as well as for next generation tumor genomic sequencing, and to help identify novel targets and/or agents for the treatment of WT and TKI-resistant non-WT GISTs.

Objective:

Evaluate and follow patients with GISTs, particularly WT and treatment-refractory non-WT, to support translational research for this rare disease

Assess disease-free intervals (DFIs) between surgical resection of disease for at least 5 years

Eligibility:

Participants with histologically confirmed or clinical presentation suspicious of GIST.

Design:

Prospective cohort study

Participants with histologically confirmed or clinical presentation suspicious of GIST will enroll on study and will have active surveillance every 9-15 months for up to 10 years prior to and up to 5 years after surgical resection and/or cytoreduction. As participants may have multiple resections during the course of the study, 5-year surveillance post-surgery may be initiated multiple times, relative to the last resection performed.

All participants enrolled will be evaluated for tumor resection or cytoreduction at the start of study and if appropriate, will be offered surgery, otherwise they will be on active surveillance until surgical resection or cytoreduction is clinically indicated.

It is expected that approximately 30-40 patients per year may enroll on this trial; the accrual ceiling will be set at 400 to permit accrual over a 10-year period.

Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis

Prospective Study of Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Patients with non-WT GIST and WT GIST will have the durations of the DFIs described both within each patient as their own control and across patients. Analyses will be done separately for those with WT GIST and those with non-WT GIST as well as for all patients combined.

Surveillance every 6-12 months and time of surgery, by tumor measurement and imaging studies, to assess disease-free intervals (DFIs) between surgical resection of disease for at least 5 years.

Characterization of the genomic and clinicopathologic features associated with GISTs.

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia	NCT00782067	Leukemia	Midostaurin (PK...	18 Years -	Novartis
Surgery in Gastrointestinal Stromal Tumors (GISTs) for Treatment, Tumor Modeling, and Genomic Analysis	NCT04557969	Gastric Cancer Gastric Neoplas... Gastrointestina... Gastrointestina... Gastrointestina...		6 Years -	National Institutes of Health Clinical Center (CC)

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