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

Hematologic Neoplasms

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

midostaurin

MAP requests are initiated by a treating physician.https:// www.novart is.com/healthcare-professionals/managed-access-programs.

The purpose of this registration is to list Managed Access Programs (MAPs) related to PKC4, Midostaurin.

* CPKC412A2001X - No longer available- An open-labeled, multi-center, Expanded Treatment Protocol (ETP) of midostaurin (PKC412) in patients 18 years of age or older with newly-diagnosed FLT3-mutated acute myeloid leukemia (AML) who are eligible for standard induction and consolidation chemotherapy
* CPKC412AUS56X - No longer available - An open-label, multi-center, Expanded Treatment Protocol of Midostaurin (PKC412) in adult patients with newly diagnosed Fms-like tyrosine kinase receptor (FLT3) mutated Acute Myeloid Leukemia (AML) who are eligible for standard induction and consolidation chemotherapy.
* CPKC412A2407I - Available - Managed Access Program (MAP) Cohort Treatment Plan CPKC412A2407I to provide access to midostaurin (PKC412) for patients 18 years of age and older with newly-diagnosed FLT3-mutated AML and eligible for induction and consolidation chemotherapy
* CPKC412D2001M - Available - Managed Access Program (MAP) to provide access to Midostaurin (PKC412), for an individual patient with aggressive systemic mastocytosis (ASM), mast cell leukemia (MCL) or mast cell sarcoma (MCS)

Managed Access Programs for PKC412, Midostaurin

Avapritinib tablets for oral administration. Avapritinib will be dosed daily for 28 day cycles.

Avapritinib

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:, dose-escalation (Part 1) and expansion (Part 2).

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

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

Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 8 and 24 hrs post dose (plus 10 and 48 hrs post dose in Part 2) on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1

Including complete remission (CR), CR with partial recovery of peripheral blood (CRh), partial remission (PR) and clinical improvement (CI) using modified International Working Group Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European competence network on mastocytosis (ECNM) criteria; and duration of response (DOR)

Including morphologic complete remission (mCR), morphologic CR with partial recovery of peripheral blood (mCRh), and morphologic partial remission (mPR) based on Pure Pathologic Response

Blueprint Medicines Corporation

Heart and Blood Diseases

Telangiectasis

Urticaria

Mastocytosis, Cutaneous

Mastocytoma

Urticaria Pigmentosa

Cutaneous Mastocytosis

Anthony L Boral, MD, PhD

The Mast Cell Connect Registry is a voluntary, observational database that will capture demographic, socioeconomic, and disease information directly from patients with mastocytosis via a secure web-based tool. No experimental intervention is involved.

Mastocytosis is an extremely rare and heterogeneous spectrum of diseases characterized by the buildup of genetically altered mast cells. Patients experience a wide range of symptoms and in some cases, mast cell buildup can lead to organ dysfunction and failure. Current treatments address disease symptoms and not the underlying cause. To facilitate the development of new therapies for mastocytosis, it is important for the community to support clinical trials and to document the impact of the disease, including disease natural history and the impact on patients, in a systematic way. Mast Cell Connect is a web-based registry that allows mastocytosis patients and caregivers to enter information about the experience of the patient living with mastocytosis directly into an online data collection tool.

The Mast Cell Connect Registry allows mastocytosis patients and caregivers to enter information about the experience of the patient living with mastocytosis directly into a web-based data collection tool. Two forms of data will be collected: responses to surveys administered on the web-based portal, and de-identified data curated from medical reports uploaded by patients or their caregivers.

Mast Cell Connect: A Registry for Patients With Mastocytosis

PatientCrossroads

Patients with advanced systemic mastocytosis who received treatment with avapritinib as part of the BLU-285-2101 and BLU-285-2202 studies

Patients with advanced systemic mastocytosis that received best available therapy

BLU-285-2405 is a multi-center, synthetic control, observational and retrospective study designed to compare clinical outcomes for avapritinib compared with best available therapy for patients with AdvSM.

Retrospective Study Assessing the Effect of Avapritinib Versus Best Available Therapy in Patients With AdvSM

An External Control, Observational, Retrospective Study Assessing the Effect of Avapritinib Compared With Best Available Therapy for Patients With Advanced Systemic Mastocytosis

Overall Survival defined as time from initiation of systemic treatment to death from any cause

DOT, defined as the duration from initiation of line of systemic treatment to discontinuation of same line of treatment for any reason and;

TtNTL, defined as the time from initiation of the line of systemic treatment to the initiation of the next line of treatment

Change in serum tryptase concentration, defined as change in serum tryptase from baseline, for each line of therapy

AEs that result in treatment modification or discontinuation, hospitalization, or death according to evaluation of responsible physician

Analysis Group, Inc.

Antibodies

Immunoglobulins

Brentuximab Vedotin

Immunoconjugates

Antineoplastic Agents, Immunological

Immunotoxins

Immunologic Factors

Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.

Brentuximab vedotin

Jason Gotlib

This pilot clinical trial studies brentuximab vedotin in treating patients with advanced systemic mastocytosis or mast cell leukemia. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them

Brentuximab vedotin is an antibody with a covalently attached toxin. The antibody portion targets the protein CD30 on the surface of cells, and the toxin acts against those cells.

PRIMARY OBJECTIVES:

I. To evaluate the response rate to SGN-35 (brentuximab vedotin) in patients with tumor necrosis factor receptor superfamily, member 8 (CD30+) advanced systemic mastocytosis (SM) (ASM or mast cell leukemia \[MCL\] with or without an associated hematological clonal non-mast cell lineage disease \[AHNMD\]).

SECONDARY OBJECTIVES:

I. To evaluate the tolerability and safety profile of SGN-35 in patients with SM.

II. To evaluate expression of CD30 on neoplastic mast cells before and during therapy with SGN-35.

III. To evaluate changes in mastocytosis related symptom scores and quality of life (QOL) using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF).

IV. To evaluate the duration of response (DoR) and time to response (TTR). V. To evaluate progression-free survival (PFS).

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 weeks for 1 year and then every 12 weeks thereafter.

Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia

A Study of Brentuximab Vedotin (SGN-35) in CD30-Positive Systemic Mastocytosis With or Without an Associated Hematological Clonal Non-Mast Cell Lineage Disease (AHNMD)

Overall response rate (ORR) is sum of complete response (CR); partial response (PR); and clinical improvement (CI) in 1 year, ie, ORR=CR+PR+CI. The outcome is the number of participants without dispersion.

CR is following with response duration(RD) ≥12 weeks (wk)

* No mast cell disease
* Tryptase \<20 ng/mL
* Neutrophils ≥1x10e9/L with normal differential
* Hemoglobin ≥11 g/dL
* Platelets ≥100x10e9/L
* No hepatosplenomegaly
* No systemic mastocytosis(SM)-related organ damage PR is following with RD ≥12wk
* Neither CR or progressive disease(PD)
* Neoplastic mast cells reduced ≥50%
* Tryptase reduced ≥50%
* 1+ disease finding resolved CI is following with RD ≥12wk
* Neither CR; PR; or PD
* 1+ of findings above Stable disease (SD) Not CR, PR, Cl, or PD Progressive disease (PD)

Any of:

* Worsening organ damage
* Doubling of laboratory abnormality
* New transfusion dependence of ≥4 units red cells or platelets at 8wk

  •+ ≥100% in transfusions for 8wk
* 10-cm+ splenomegaly

Toxicity was assessed as the number of adverse events considered possibly, probably, or definitely-related to treatment with brentuximab vedotin. The outcome is reported as the total number of related events, a number without dispersion, and the number of related events (without dispersion) considered to be either a hematologic toxicity or non-hematologic toxicity.

The presence of the CD30 marker (epitope) on neoplastic (cancerous) mast cells in core bone marrow biopsy samples was assessed by immunohistochemical methods, before and after brentuximab vedotin treatment. CD30 is a member of the TNF-receptor (TNF-R) superfamily, and is a transmembrane glycoprotein receptor that is normally at very low levels on the surface of activated T-cells. Overexpression of the CD30 marker is indicative of T-cell lymphoproliferative disorders and neoplastic mast cells, and the effect of a particular treatment on CD30 expression may be related to the efficacy of that treatment. The outcome is reported as the median percentage change in the level of CD30 detected, reported with full range.

The clinical effect of patient symptoms associated with systemic mastocytosis or mast cell leukemia were assessed with the patient-reported outcome survey entitled Myeloproliferative Neoplasm Symptom Assessment Form with Mast Cell Disorder Symptoms \[(MPN-SAF(MCD)\]. The MPN-SAF(MCD) is a 36-question survey, with possible responses ranged from 0 to 10, with 0 indicating not present or no effect; 1 meaning present but most favorable; and 10 meaning worst imaginable (least favorable). Total range is 0 to 360, with 0 being best possible, and 360 being worst possible. Total symptom score is calculated as the sum of the individual survey scores reported at baseline and after treatment, with lower numbers indicating less effect, and larger numbers indicated greater effect. The outcome is reported as mean score value with dispersion.

Overall quality of life (QoL) was assessed by a single specific question from the 36-question Myeloproliferative Neoplasm Symptom Assessment Form with Mast Cell Disorder Symptoms \[(MPN-SAF(MCD)\] survey. Possible responses for theQoL question range from 0 to 10, with 0 indicating "as good as it can be" (most favorable), and 10 meaning "as bad as it can be" (least favorable). The QoL score was obtained at baseline and after treatment. The outcome is reported as mean score with dispersion.

Duration of response (DOR) is defined as the time from the start of the first confirmed response until the date of the first documented and confirmed disease progression or death due to ASM or MCL. For participants with a confirmed clinical response, the outcome was to be reported as the median DOR with standard deviation.

Time to response (TTR) is defined as the time from the date of start of treatment to the date of first confirmed response. For participants with a confirmed clinical response, the outcome was to be reported as the median TTR with standard deviation.

Progression-free survival (PFS) is defined as the time from the date of start of treatment until disease progression; death; or initiation of new therapy. The outcome is reported as the mean number of days of PFS, with 95% confidence interval.

Progressive disease (PD) is any of the following:

* Worsening of any organ damage
* Doubling of any laboratory abnormality
* New transfusion dependence of ≥ 4 units red cells or platelets at 8 wk
* ≥ 100% increase in transfusions for 8 wk
* 10-cm+ splenomegaly

Seagen Inc.

Jason Robert Gotlib

Professor of Medicine (Hematology)

Age, Categorical

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Jason R. Gotlib

1 of 10 participants were not evaluable due to early death during Cycle 1 (considered unrelated to study treatment)

Overall Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement)

Total related adverse events (toxicities)

Related hematologic toxicity

Related non-hematologic toxicity

Brentuximab Vedotin Toxicity

CD30 marker data was not obtained for some participants.

Percent Change of CD30 Expression on Neoplastic Mast Cells

Baseline (Pre-treatment)

After Treatment

Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score

Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)

Duration of response (DOR) can not be determined if no participants had a response.

Duration of Response (DOR)

Time to response (TTR) can not be determined if no participants had a response.

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
Managed Access Programs for PKC412, Midostaurin	NCT05219266	FMS-Like Tyrosi... Acute Myeloid L... Aggressive Syst... Mast Cell Leuke... Systemic Mastoc...	midostaurin	18 Years -	Novartis
(EXPLORER) Study of BLU-285 in Patients With Advanced Systemic Mastocytosis (AdvSM) and Relapsed or Refractory Myeloid Malignancies	NCT02561988	Aggressive Syst... Systemic Mastoc... Mast Cell Leuke... Relapsed or Ref...	Avapritinib	18 Years -	Blueprint Medicines Corporation
Mast Cell Connect: A Registry for Patients With Mastocytosis	NCT02620254	Mastocytosis		-	Blueprint Medicines Corporation
Mast Cell Connect: A Registry for Patients With Mastocytosis	NCT02620254	Mastocytosis		-	Blueprint Medicines Corporation
Retrospective Study Assessing the Effect of Avapritinib Versus Best Available Therapy in Patients With AdvSM	NCT04695431	Advanced System... Aggressive Syst... Systemic Mastoc... Mast Cell Leuke...		18 Years -	Blueprint Medicines Corporation
Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia	NCT01807598	Aggressive Syst... Mast Cell Leuke... Systemic Mastoc...	Brentuximab ved...	18 Years -	Stanford University

Spots Global Cancer Trial Database for aggressive systemic mastocytosis