Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Disease Progression

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Real-world (RW) patients with RRMM who have either at least three prior lines of therapy (LOT) and are triple-class exposed (3L+/TCE), or are triple-class refractory (TCR), meet similar inclusion/exclusion criteria used to establish phase 2 cohort 2 of the R5458-ONC-1826 trial, and are initiating currently available therapies.

No study treatment will be administered on this study.

Non-Interventional

Clinical Trial Management

Primary Objective:

1. To describe the distribution of treatment regimens and objective response rate (ORR) in a Benchmark Cohort of real-world patients with relapsed/refractory multiple myeloma (RRMM) who initiate treatment after meeting the following criteria: (1) have either (a) at least three prior lines (3L) and are triple-class exposed (TCE), or (b) are triple-class refractory (TCR), and (2) meet similar inclusion/exclusion criteria to patients in phase 2 cohort 2 of the R5458-ONC-1826 (NCT03761108) trial.

Secondary Objectives:

1. To describe additional outcomes (duration of response \[DOR\], progression-free survival \[PFS\], overall survival \[OS\], and time to next treatment \[TTNT\]) in the same Benchmark Cohort population described in the primary objective.
2. To describe distribution of treatment regimens, ORR, DOR, PFS, OS, and to compare ORR, PFS, OS, and TTNT in an Analysis Cohort consisting of real-world patients derived from the Benchmark Cohort described above who are weighted to align with the characteristics of patients in phase 2 cohort 2 of the R5458-ONC-1826 (NCT03761108) trial. Comparative analyses of PFS and OS will be performed conditional on sufficient maturity of survival data in the R5458-ONC-1826 (NCT03761108) trial at the time of analysis.

Real-World Clinical Outcomes in Patients With Relapsed/Refractory Multiple Myeloma

A Study to Characterize Treatment Patterns and Real-World Outcomes in Heavily Pretreated Patients With Relapsed and Refractory Multiple Myeloma (RRMM) and Similar Clinical Characteristics to Patients in the Phase 2 Cohort 2 of the R5458-ONC-1826 Trial

Defined as stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR)

Defined as time from the date of the first documented response (best overall response of sCR, CR, VGPR, PR) until the first date of progressive disease (PD) by International Myeloma Working Group (IMWG) or death due to any cause, whichever occurs first.

Defined as time from the start of study treatment until the first date of PD by IMWG, or death due to any cause, whichever occurs first.

OS is measured from the start of study treatment until death due to any cause.

Defined as time from the start of study treatment until the initiation of the subsequent LOT.

Regeneron Pharmaceuticals

Nervous System Diseases

Brain Neoplasms

Genetic Predisposition to Disease

Medulloblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Disease Susceptibility

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Tumor, Childhood

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Micronutrients

Cyclophosphamide

Carboplatin

Doxorubicin

Liposomal doxorubicin

Leucovorin

Vincristine

Cisplatin

Lomustine

Vinblastine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Radiotherapy and reduced-intensity maintenance chemotherapy. Total treatment duration is 39 weeks.

Radiotherapy with carboplatin or radiotherapy without carboplatin and maintenance chemotherapy.

Total treatment duration is 48 weeks.

Radiotherapy adapted to age and metastatic Status and maintenance chemotherapy adapted to age.

Total treatment duration is 39 to 48 weeks.

Reduced chemotherapy with Doxorubicin, VCR, HD-MTX, Carboplatin, and MTX intraventricularly Stratification of radiotherapy according to

* presence of metastasis
* germline mutation in TP53 (including mosaicism) Maintenance chemotherapy with VBL Total treatment duration is 1 year

Brain - 23.40 Gy in 13 daily fractions of 1.80 Gy Spine - 23.40 Gy in 13 daily fractions of 1.80 Gy Primary tumour boost - 30.60 Gy in 17 daily fractions of 1.80 Gy Total dose - 54 Gy Duration of radiotherapy 6 weeks

LR Arm after Amendment (Protocol version 11- 17 Nov 2014):

Brain - 18.0 Gy in 10 daily fractions of 1.80 Gy Spine - 18.0 Gy in 10 daily fractions of 1.80 Gy Primary tumour boost - 36.0 Gy in 20 daily fractions of 1.80 Gy Total dose - 54 Gy Duration of radiotherapy 6 weeks

Radiotherapy without Carboplatin

Starts 6 weeks after radiotherapy. 6 cycles alternating Regimen A and Regimen B. Regimen A (cycles 1, 3, 5): cisplatin 70 mg/m2 day 1, CCNU 75 mg/m2 day 1, vincristine 1.5 mg/m2 days 1, 8 and 15, Regimen B: (cycles 2, 4, 6): cyclophosphamide 1 x 1000 mg/m2 days 1-2, vincristine 1.5 mg/m2 day 1.

Interval after cycle A: 6 weeks, after cycle B: 3 weeks, for a total duration of 27 weeks.

Cumulative doses of chemotherapy drugs: cisplatin 210 mg/m2, lomustine (CCNU) 225 mg/m2, vincristine 18 mg/m2, cyclophosphamide 6 g/m2.

Reduced-intensity maintenance chemotherapy

Brain - 23.40 Gy in 13 daily fractions of 1.80 Gy Spine - 23.40 Gy in 13 daily fractions of 1.80 Gy Primary tumour boost - 30.60 Gy in 17 daily fractions of 1.80 Gy Total dose - 54 G Carboplatin 35 mg/m2 5 times/week.

Radiotherapy with Carboplatin

Starts 6 weeks after radiotherapy. 8 cycles alternating Regimen A and Regimen B. Regimen A (cycles 1, 3, 5, 7): cisplatin 70 mg/m2 day 1, CCNU 75 mg/m2 day 1, vincristine 1.5 mg/m2 days 1, 8 and 15 Regimen B: (cycles 2, 4, 6, 8): cyclophosphamide 1 x 1000 mg/m2 days 1-2, vincristine 1.5 mg/m2 day 1.

Interval after cycle A: 6 weeks, after cycle B: 3 weeks. Duration 36 weeks. Cumulative doses of chemotherapy drugs: cisplatin 280 mg/m2, lomustine (CCNU) 300 mg/m2, vincristine 24 mg/m2, cyclophosphamide 8 g/m2, carboplatin 1050 mg/m2 (in randomized patients).

Maintenance chemotherapy

Brain - 23.4 Gy in 13 daily fractions of 1.8 Gy Spine - 23.4 Gy in 13 daily fractions of 1.8 Gy Primary tumour boost - 30.6 Gy in 17 daily fractions of 1.8 Gy Boost to macroscopic metastases - 21.6 Gy in 12 daily fractions of 1.8 Gy Total dose to primary tumour - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to cranial metastases - 45.0 Gy in 25 daily fractions of 1.8 Gy Total dose to spinal metastases - 45.0 Gy in 25 daily fractions of 1.8 Gy

WNT-HR < 16 years

Brain - 36.0 Gy in 20 daily fractions of 1.8 Gy Spine - 36.0 Gy in 20 daily fractions of 1.8 Gy Primary tumour boost - 18.0 Gy in 10 daily fractions of 1.8 Gy Metastases boost (cranial) - 14.4 Gy in 8 daily fractions of 1.8 Gy Metastases boost (spinal) - 9.0 Gy in 5 daily fractions of 1.8 Gy Total dose to primary tumour - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to cranial metastases - 50.4 Gy in 30 daily fractions of 1.8 Gy Total dose to spinal metastases - 45.0 Gy in 25 daily fractions of 1.8 Gy

WNT-HR >= 16 years

Doxorubicin 37,5mg/m² in 24h-infusion, days 1 and 2 (If administration of doxorubicin is not deemed appropriate, doxorubicin can be substituted by carboplatin 200mg/m²) VCR 1,5mg/m² (max. dose 2mg) in short infusion, days 1, 15, 29, 43 HD-MTX 5g/m²in two doses (0.5g/m² in 0.5h and 4.5g/m² in 23.5h), days 15 and 29 (+ Leucovorin) Carboplatin 200mg/m² in 1h-infusion, days 43, 44, and 45 MTX 2mg intraventricularly, days 1-4, 15, 16, 29, 30, 43-46

Induction Chemotherapy

* with VCR 1,5 mg/m2 (max. 2mg), once weekly during radiotherapy, for a maximum of 6 weeks
* clinical target volume (CTV): safety margin along typical spread 10 mm: 23.4.Gy in 13 fractions to CTV.
* focal RT boost to tumour bed and residual tumour (GTV) (boost: 30.6 Gy in 17 daily fractions of 1.8 Gy)

SHH-TP53 M0

craniospinal radiotherapy with boost to tumour bed, residual tumour and metastatic deposits with VCR 1,5 mg/m2 (max. 2mg), once weekly during radiotherapy, for a maximum of 6 weeks Brain - 23.4 Gy in 13 daily fractions of 1.8 Gy Spine - 23.4 Gy in 13 daily fractions of 1.8 Gy Primary tumour boost - 30.6 Gy in 17 daily fractions of 1.8 Gy Metastases boost (cranial) - 30.6 Gy in 17 daily fractions of 1.8 Gy Metastases boost (spinal) - 21.6 Gy in 12 daily fractions of 1.8 Gy Total dose to primary tumour - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to cranial metastases - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to spinal metastases - 45.0 Gy in 25 daily fractions of 1.8 Gy

SHH-TP53 M+ (germline)

craniospinal radiotherapy with boost to tumour bed, residual tumour and metastatic deposits with VCR 1,5 mg/m2 (max. 2mg), once weekly during radiotherapy, for a maximum of 6 weeks Brain - 36.0 Gy in 20 daily fractions of 1.8 Gy Spine - 36.0 Gy in 20 daily fractions of 1.8 Gy Primary tumour boost - 18.0 Gy in 10 daily fractions of 1.8 Gy Metastases boost (cranial) - 18.0 Gy in 10 daily fractions of 1.8 Gy Metastases boost (spinal) - 9.0 Gy in 5 daily fractions of 1.8 Gy Total dose to primary tumour - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to cranial metastases - 54.0 Gy in 30 daily fractions of 1.8 Gy Total dose to spinal metastases - 45 Gy in 25 daily fractions of 1.80 Gy

SHH-TP53 (somatic)

Weekly VBL (5mg/m², max. 10mg/dose) for 24 weeks

Vinblastin Maintenance

Francois Doz, Prof. Dr.

Till Milde, Dr. med.

The study PNET 5 MB has been designed for children with medulloblastoma of standard risk (according to the risk-group definitions which have been used so far; e.g. in PNET 4). With the advent of biological parameters for stratification into clinical medulloblastoma trials, the ß-catenin status will be the only criterion according to which study patients will be assigned to either treatment arm PNET 5 MB - LR or to PNET 5 MB - SR, respectively. The initial diagnostic assessments (imaging, staging, histology, and tumor biology) required for study entry are the same for both treatment arms. With the amendment for version 12 of the protocol, patients who have a WNT-activated medulloblastoma with clinically high-risk features can be included in the PNET 5 MB WNT-HR study, and patients with a high-risk SHH medulloblastoma with TP53 mutation (both somatic or germline including mosaicism) can be included in the PNET5 MB SHH-TP53 study.

Data on patients with pathogenic germline alteration or cancer predisposition syndrome, who cannot be included in any prospective trial due to unavailability or due to physician or family decision, can be documented within the observational PNET 5 MB registry.

The aim of the LR-study is to confirm the high rate of event-free survival in patients between the ages of 3 to 5 years and less than 22, with 'standard risk' medulloblastoma with a low-risk biological profile. Patients eligible for the study will be those with non-metastatic medulloblastoma (by CSF cytology and centrally reviewed MRI imaging) at diagnosis and low-risk biological profile, defined as ß-catenin nuclear immuno-positivity by immuno-histochemistry (IHC). Patients will have undergone total or near-total tumour resection and will receive conventionally fractionated (once a day) radiotherapy with a dose of 54 Gy to the primary tumor and 18.0 Gy to the craniospinal axis. Following radiotherapy, patients will receive a reduced-intensity chemotherapy with a total of 6 cycles of chemotherapy consisting of 3 courses of cisplatin, CCNU and vincristine alternating with 3 courses of cyclophosphamide and vincristine.

The aim of the SR-study is to test whether concurrent carboplatin during radiotherapy followed by 8 cycles of maintenance chemotherapy in patients with 'standard risk' medulloblastoma with an average-risk biological profile may improve outcome. Patients eligible for the study will be those with non-metastatic medulloblastoma (by CSF cytology and centrally reviewed MRI imaging) at diagnosis and average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC. Patients will have undergone total or near-total tumour resection and will receive conventionally fractionated (once a day) radiotherapy with a dose of 54 Gy to the primary tumor and 23.4 Gy to the craniospinal axis. Following radiotherapy, patients will receive a modified-intensity chemotherapy with a total of 8 cycles of chemotherapy consisting of 4 courses of cisplatin, CCNU and vincristine alternating with 4 courses of cyclophosphamide and vincristine.

The primary aim of the WNT-HR study is to maintain a 3-year EFS over 80 %. The small number of patients does not allow neither conventional methods of test size and power, nor strict stopping rules. The 3-year EFS will be estimated by the Kaplan-Meier method at the end of the trial and its two-sided 95 % confidence interval will be calculated.

The primary endpoint of the SHH-TP53 study is event-free survival (EFS). The aim of the study is the comparison of EFS between patients receiving a dose reduced induction chemotherapy, radiotherapy and maintenance chemotherapy and a historic population from unpublished data.

International Society of Paediatric Oncology (SIOP) PNET 5 Medulloblastoma

AN INTERNATIONAL PROSPECTIVE TRIAL ON MEDULLOBLASTOMA (MB) IN CHILDREN OLDER THAN 3 TO 5 YEARS WITH WNT BIOLOGICAL PROFILE (PNET 5 MB - LR and PNET 5 MB - WNT-HR), AVERAGE-RISK BIOLOGICAL PROFILE (PNET 5 MB -SR), OR TP53 MUTATION, AND REGISTRY FOR MB OCCURRING IN THE CONTEXT OF GENETIC PREDISPOSITION

Defined in 5 categorical variables:

no relapse, local relapse, distant relapse, local and distant relapse, death

measured as

1. subfertility (FSH \> 15 IU/L)
2. endocrine deficits (hormone supplementation necessary)
3. growth retardation (calculated as the difference in height standard deviation score from diagnose) 2 and 5 years after diagnosis and age of 18 years

measured on audiogram performed 2 years after diagnosis, grading according to Chang ototoxicity grading (Chang and Chinosornvatana 2010)

Measured as

1. presence, duration, and therapy of hydrocephalus symptoms (pre- and post-operatively)
2. presence of posterior fossa syndrome (cerebellar mutism survey after surgery, before radiotherapy)
3. cerebellar symptoms (brief ataxia rating scales 2 and 5 years after diagnosis and age of 18 years)
4. presence of symptoms for brain nerve dysfunction (2 and 5 years after diagnosis and age of 18 years)

measured with standardized questionnaires/ scores:

1. HUI3 (health status)
2. BRIEF (executive functions)
3. SDQ (behavioural outcome)
4. PedsQL (quality of life)
5. QLQ-C30 (quality of life)
6. MEES (neurological function, educational provision)
7. MFI (fatigue) 2 and 5 years after diagnosis and age of 18 years

measured as timely delivery of chemotherapy number of interruptions days during radiotherapy toxicities within 8 weeks after end of radiotherapy

measured by central MRI review postoperatively

measured 2 years after diagnosis grades 0, 1, 2, 3, 4

Deutsche Kinderkrebsstiftung

Universitätsklinikum Hamburg-Eppendorf

Neoplastic Cells, Circulating

Neoplasm Metastasis

Neoplastic Processes

Anticoagulants

Edetic Acid

Pentetic Acid

Blood samples (3 ethylenediaminetetraacetic acid (EDTA) tubes with a volume of 7.5 ml blood each) will be processed for CTC isolation and characterization, ranging from molecular analysis to culture and drug screen.

Blood samples

In case of tumor resection, 3 EDTA tubes (5 ml) will be withdrawn from the tumor draining vessels for CTC isolation and characterization, ranging from molecular analysis to culture and drug screen.

Samples from tumor draining vessels

Marcus Vetter, PD Dr. med.

Nicola Aceto, Prof. Dr. med.

Christian Kurzeder, PD Dr. med.

Fabienne Schwab, Dr. med

Viola Heinzelmann-Schwarz, Prof. Dr. med

Christoph Rochlitz, Prof. Dr. med.

Julia Landin, Dr. med.

Alfred Zippelius, Prof. Dr. med.

Heinz Läubli, PD Dr. med.

Walter Weber, Prof. Dr. med.

Dörthe Schaefer-Rohr, Dr. med.

Homen Begovic, Dr. med.

Christine Wenk, Dr. med.

Daniel Steffens, Dr. med.

Anna Schollbach, Dr. med.

Ilker Acemoglu, Dr. med.

Simone Münst, PD Dr. med.

Tatjana Vlajnic, Dr. med.

Robert Rosenberg, Prof. Dr. med.

Emanuel Burri, PD Dr. med.

This observational study with circulating tumor cells (CTC) count, isolation and analysis at several time points during disease progression is to investigate the role and biology of CTCs and clusters of CTCs in different cancer types. It also evaluates the role of CTCs as biomarkers, and aims at the identification of key signaling networks that are active in CTCs.

CTC cultures stored in the refrigerator. A "Biobank Reglement" is enclosed to this protocol.

Circulating Tumor Cells (CTC) in Cancer

Change in circulating tumor DNA (ctDNA) from blood samples

overall survival (OS) in heterogeneous cancer population

progression free survival (PFS) in the different cancer cohorts with different treatment regimes

University Hospital, Basel, Switzerland

Respiratory Tract (Lung and Bronchial) Diseases

Pleural Effusion

Pleural Effusion, Malignant

Mesothelioma

Mesothelioma, Malignant

Carcinoma

Adenoma

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Pleural Diseases

Malignant Mesothelioma

LMB-100

Immunotoxins

Immunoconjugates

LMB-100 at escalating/de-escalating doses + MSLN testing

Cytoreductive surgery: minimally invasive (VATS/robotic) or open (thoracotomy)

Cytoreductive surgery

1000 mcg/mL (DL1) post-operative dose as a single 90-minute normothermic intrathoracic perfusion using a closed circuit and roller pump with a heat exchanger following maximal cytoreductive surgery

Performed at screening to determine mesothelin expression; separate testing of tumor mesothelin expression will be assessed retrospectively in resected tumor tissues. The device is not diagnostic; protocol assessment of mesothelin expression status will only be used to help to increase the possibility that all persons enrolling on the study might derive benefit from therapy.

Immunohistochemical Assay for Mesothelin

David S Schrump, M.D.

Background:

Cancers that spread into the thin tissue lining your lungs (pleura) cause serious illness. They often recur when removed. These tumors include malignant pleural mesothelioma (MPM), caused by exposure to asbestos and related fibers. Malignant pleural effusions (MPEs) are caused when cancers in other parts of the body spread to the lungs and pleura. Many people diagnosed with pleural tumors survive less than a year.

Objective:

To test the safety of a study drug (LMB-100) in people. LMB-100 may help stop pleural tumors from recurring after surgery.

Eligibility:

People aged 18 years or older diagnosed with MPM or related cancer that has spread into the pleura.

Design:

Participants will undergo screening. They will have a physical exam with blood and urine tests. They will have CT scans. They will have tests that measure the how their heart and lungs function. They will provide a sample of tumor tissue to determine if their tumor expresses a protein called mesothelin.

Participants will undergo standard surgery to maximally remove the plural tumors. Then they will have LMB-100 pumped into their chest. The liquid will rinse the chest wall, diaphragm, heart sac, and surface of the lungs for 90 minutes. Then the liquid will be drained and the surgical incisions closed. The participants will be under anesthesia during this procedure.

Participants will remain in the intensive care unit for a least 48 hours. They will remain in the hospital for up to a week or more until recovered enough to be safely discharged.

Participants will return for regular follow-up visits for 2 years.

Background

* Malignant pleural mesotheliomas (MPM) are aggressive cancers with a high predilection for intrapleural recurrences despite potentially curative resections.
* Pleural metastases and associated malignant pleural effusions (MPE) cause considerable morbidity and mortality in patients with lung and esophageal cancers, gastrointestinal, pancreatic, and ovarian carcinomas, as well as sarcomas.
* Mesothelin (MSLN), a tumor differentiatio antigen, is expressed in over 95% of epithelioid MPM, as well as 80% of thymic carcinomas, 50% of lung and gastroesophageal cancers, 75% of pancreatic carcinomas, and 30% of ovarian carcinomas and synovial sarcomas.
* Mesothelin is an attractive target for cancer therapy due to its limited expression in normal human tissues and effects on invasion and metastasis of cancer cells.
* LMB-100 is a novel recombinant anti-mesothelin immunotoxin containing a humanized fragment of an anti-mesothelin Fab conjugated to a de-immunized Pseudomonas exotoxin A (PEA) which exhibits broad activity against cancer lines and tumor xenografts expressing mesothelin.
* Despite de-immunizing modifications, LMB-100 still induces neutralizing antibodies that prevent repeated systemic administration of this immunotoxin.
* Local (intraperitoneal) administration of LMB-100 can eradicate low-volume carcinomatosis in a murine model of minimal residual disease.
* Conceivably, intracavitary administration of LMB-100 following cytoreductive surgery may enhance local control of pleural-based malignancies that express mesothelin while minimizing systemic exposure of the immunotoxin.

Primary Objective

-To identify maximum tolerated dose (MTD) and evaluate the toxicities of LMB-100 administered by 90-minute normothermic, intrapleural perfusion in participants with mesothelin-positive MPM, or MPE from cancers that express mesothelin.

Eligibility

* Age \>= 18 years
* Histologically confirmed mesothelioma, or other mesothelin-positive malignancy metastatic to the pleura, potentially amenable to cytoreductive surgery and subsequent intrapleural perfusion.
* No systemic or local therapy for their malignancy within 3 weeks prior to protocol treatment.
* Adequate organ function and cardiopulmonary reserve to tolerate intended resection.
* No active infections.
* No active central nervous system (CNS) metastases.

Design

* Participant s will undergo maximal cytoreductive surgery for their malignancies by open or minimally invasive procedures as dictated by histologic, anatomic, and physiologic parameters.
* Thereafter, LMB-100 will be administered by 90-minute normothermic intrathoracic perfusion using a closed circuit and roller pump with a heat exchanger.
* LMB-100 levels will be measured in pulmonary lavage and plasma.
* The dose of LMB-100 will be increased using a 3 plus 3 design to define MTD.
* Once the MTD has been defined, the enrollment will be expanded to more fully define toxicities and evaluate time to disease progression and overall survival (OS) using 2 separate cohorts of participants with MPM and pleural effusions from other malignances (MPE).
* The accrual ceiling will be set at 42.

Phase I Evaluation of Immunotoxin LMB-100 Administered by Normothermic, Intrapleural Perfusion Following Cytoreductive Surgery in Participants With Pleural Mesotheliomas, or Pleural Effusions From Cancers Expressing Mesothelin

.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.

List of adverse event frequency, type, and grade Safety data based on toxicity grades and types of toxicity will be reported by dose level during dose escalation.

Cytoreductive surgery until time of documented clinical recurrence (radiographically or pathologically) Progression free survival (PFS): 2 year PFS probability will be calculated from the on-study date through 2 years after initiation of study therapy using the Kaplan-Meier method. Overall Survival (OS): 3 year OS probability from the on-study date through 3 years after initiation of study therapy

Pharmacokinetic accumulation of free and total plasma concentrations of LMB-100 will be measured using validated ligand-binding assays analyzed in the blood (plasma)and pulmonary lavage at protocol time points. Analyses will be performed retrospectively in batched samples or at the end of the trial.

National Cancer Institute (NCI)

Behaviors and Mental Disorders

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphatic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Quality of Life

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Chromosome 17p Deletion

Venetoclax

Venetoclax was administered orally once daily (QD) for a planned duration of up to 2 years or until disease progression; median time on treatment was 127 weeks. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.

Venetoclax tablets were to be taken orally once daily with a meal and water in the morning at approximately the same time each day. Tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Real-World Clinical Outcomes in Patients With Relapsed/Refractory Multiple Myeloma	NCT05673967	Relapsed and Re...	Non-Interventio...	18 Years -	Regeneron Pharmaceuticals
International Society of Paediatric Oncology (SIOP) PNET 5 Medulloblastoma	NCT02066220	Brain Tumors	Radiotherapy wi... Reduced-intensi... Radiotherapy wi... Maintenance che... WNT-HR < 16 yea... WNT-HR >= 16 ye... Induction Chemo... SHH-TP53 M0 SHH-TP53 M+ (ge... SHH-TP53 (somat... Vinblastin Main...	3 Years - 21 Years	Universitätsklinikum Hamburg-Eppendorf
Circulating Tumor Cells (CTC) in Cancer	NCT04520672	Cancer	Blood samples Samples from tu...	18 Years -	University Hospital, Basel, Switzerland
Phase I Evaluation of Immunotoxin LMB-100 Administered by Normothermic, Intrapleural Perfusion Following Cytoreductive Surgery in Participants With Pleural Mesotheliomas, or Pleural Effusions From Cancers Expressing Mesothelin	NCT05375825	Malignant Pleur... Malignant Pleur... Epithelial Tumo... Pleural Effusio... Mesothelin (Msl...	Cytoreductive s... LMB-100 Immunohistochem...	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Phase I Evaluation of Immunotoxin LMB-100 Administered by Normothermic, Intrapleural Perfusion Following Cytoreductive Surgery in Participants With Pleural Mesotheliomas, or Pleural Effusions From Cancers Expressing Mesothelin	NCT05375825	Malignant Pleur... Malignant Pleur... Epithelial Tumo... Pleural Effusio... Mesothelin (Msl...	Cytoreductive s... LMB-100 Immunohistochem...	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
A Study Evaluating the Impact of Venetoclax on the Quality of Life for Subjects With Relapsed (Your Cancer Has Come Back) or Refractory (no Response to Previous Cancer Treatments) Chronic Lymphocytic Leukemia (CLL) While Receiving Venetoclax Monotherapy (a Single Agent).	NCT02980731	Chronic Lymphoc...	Venetoclax	18 Years - 99 Years	AbbVie
Stage II/III Colorectal Cancer Recurrence	NCT06314958	Colorectal Canc... Colorectal Aden... Colorectal Canc... Colorectal Canc... Colorectal Canc...	CENSURE	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for overall survival (os)