Neoplasms

Nervous System Diseases

All Conditions

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Imaging camera scan that uses reflected red light to take pictures of the amount of blood flowing in brain and the amount of oxygen in blood.

Speckle-Contrast Imaging

Jeffrey Weinberg, MD

The goal of this proposal is to test the performance of a novel optical imaging system for real-time quantitative imaging of brain function through multiple hemodynamic measures during neurosurgery.

This pilot study encompasses two sub-aims:

* Evaluate the ability of laser speckle contrast imaging to image cerebral blood flow (CBF) intraoperatively. We will image the changes in CBF in response to somatosensory stimulation. (5 patients).
* Simultaneously image hemoglobin oxygenation, blood volume, blood flow, and cerebral metabolic rate of oxygen (CMRO2) changes during somatosensory stimulation using a combined laser speckle and multi-wavelength reflectance imaging system. (5 patients).

A speckle-contrast imaging camera uses a low-power laser to check brain activity. The imaging camera uses reflected red light to take a special kind of picture of the amount of blood flowing in your brain, and the amount of oxygen in your blood. This is the first time this device has been used in brain surgery.

While "asleep" under anesthesia during an already scheduled surgery, the neurosurgeon will position the microscope to take pictures of the surgery area. The pictures will be taken after the brain is exposed, but before the rest of the surgery takes place. Researchers will shine the red light onto the brain during your surgery. The light will then be seen by the camera.

"Cortical mapping" will done, which is an established procedure used to detect important areas of the brain. Usually, a nerve in the wrist is stimulated with a very small shock of electricity and a response is detected in the brain by an electrode placed on the surface. The electrical shock administered is not dangerous or painful. It will be given while "asleep." For the experimental procedure used in this study, the same stimulation will be used, but the impulse detection will be performed using the speckle-contrast imaging camera. Researchers hope to see if the change in blood flow gives the same information as if the electrode was placed on the brain and used to detect the electricity. Doing both procedures is expected to take no more than 20 minutes. During this time, continual monitoring done by the surgeon and operating room staff.

Your participation in this study will end when the surgery is finished.

The results of this study will not be used by the surgeon during your surgery or any future treatments. These measurements are being done for research only and will not be used by the surgeon to make any decisions about your surgery.

This is an investigational study. This device is investigational and has not been approved by the Food and Drug Administration (FDA), but it has been declared safe by the National Institutes of Health. Up to 10 patients will take part in the study. All will be enrolled at M. D. Anderson.

Intraoperative Optical Imaging of Brain Function

National Institutes of Health (NIH)

National Institute of Neurological Disorders and Stroke (NINDS)

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Ganglion Cysts

Synovial Cyst

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

All Drugs and Chemicals

Lidocaine

Anesthetics

Isoflurane

26 patients who will be subjected to a neurosurgical intervention for removal of supratentorial brain tumor. Supratentorial brain tumors with shift of the mid-line \<10 mm evaluated by CT scan \[computerized tomography\] . SPGB will be performed using 2 % lidocaine before induction of anesthesia.

The anesthesia induced by IV anesthetics and maintained by Isoflurane. ICP, Jugular venous bulb oxygen saturation, and AVDO2 will be assessed every 20 minutes.

26 patients who will be subjected to a neurosurgical intervention for removal of supratentorial brain tumor. Supratentorial brain tumors with shift of the mid-line \<10 mm evaluated by CT scan \[computerized tomography\] . SPGB will be performed using normal saline.The anesthesia induced by IV anesthetics and maintained by Isoflurane. ICP, Jugular venous bulb oxygen saturation, and AVDO2 will be assessed every 20 minutes

Sphenopalatine Ganglion Block using 2% lidocaine in block group. Sphenopalatine Ganglion Block is performed by a hollow culture swab that is connected with a 21-gauge a syringe filled with three ml 2% lidocaine, inserted parallel to the floor of the nose until resistance is felt. The swab is at the posterior pharyngeal wall superior to the middle turbinate. The applicator was kept in the nostril for five to ten mins. The same procedure is done also in the second nostril SPGB using normal saline is performed in the control group

SPGB

Naglaa Abdelhaleem, MD

This study aims to investigate the effect of Sphenopalatine Ganglion Block on ICP and arterio- jugular venous oxygen difference (AJVDO2) and jugular bulb oxygen saturation (SjVO2). Throughout this study, the efficacy of Sphenopalatine Ganglion Block as scalp block in craniotomy operation will be assessed, and the effect of SPGB on cerebral hemostasis during craniotomy will be evaluated by monitoring of both ICP, AJVDO2 and SjVO2.

This study was performed in the Neurosurgical operating room and included 52 patients allocated into two groups: the treatment group (block group) and the control group (non-block group). 26 patients enrolled in block group and 26 patients in non-block group.

Intraoperative ICP monitoring by subdural ICP monitors will be done every 20 minutes in both block and non- block groups until craniotomy has been occurred, then at the time of closure of the dura . Arterio- jugular venous oxygen difference and Jugular venous bulb oxygen saturation changes will be recorded every 20 minutes in block and non- block groups throughout time of the surgery till closure of the dura.

This study will be performed in the Neurosurgical operating room and included 52 patients allocated into two groups: the treatment group (block group) and the control group (non-block group). 26 patients enrolled in block group and 26 patients in non-block group.

Intraoperative ICP monitoring by subdural ICP monitors will be done every 20 minutes in both block and non- block group.

Jugular venous bulb oxygen saturation changes will be recorded every 20 minutes in block and non- block.

Effect of SPGB on ICP and Oxygenation of Cerebral Venous Outflow in Craniotomy for Cerebral Tumors.

Effect of Sphenopalatine Ganglion Block on Intracranial Pressure and Cerebral Venous Outflow Oxygenation During Craniotomy for Supratentorial Brain Tumors.

it will be available after completion of study and publication

ICP changes checked by a subdural ICP monitor that positioned after the first burr hole at the opposite side of the tumor immediately after induction of anesthesia. ICP monitoring will be conducted every 20 minutes until time of initial craniotomy and at time of closure of the dura.

Jugular venous bulb oxygen saturation will be measured then AVDO2 will be calculated.

Zagazig University

Lecturer, Anesthesia and Surgical Intensive Care Department, Faculty of Medicine

Blood and Lymph Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

Hematinics

Cytarabine

Daunorubicin

Midostaurin

Iron-Dextran Complex

Gemtuzumab

Staurosporine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Protein Kinase Inhibitors

Phase I (Trial part MODULE): The treatment plan combines increasing doses levels of midostaurin (25/50 mg BID) and gemtuzumab ozogamicin (3 mg/m\^2 i.v. max 4.5 mg on day(s) 1, (4, 7)) with 7+3 standard chemotherapy scheme using cytarabine (200 mg/m\^2 cont. inf. i.v. on days 1 to 7) and daunorubicin (60 mg/m\^2 i.v. on days 1 to 3).

Phase II (Trial part MAGNOLIA): midostaurin (recommended phase II dose, RP2D) is combined with treatment standard (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v.) plus GO (recommended phase II dose, RP2D) in CBF AML

Phase II (Trial part MAGNOLIA): treatment standard of CBF AML (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v. plus GO (3 mg/m\^2 i.v. max 4.5 mg) on days 1, 4, 7). No additional Midostaurin is given.

Phase II (Trial part MAGMA): GO (recommended phase II dose, RP2D) is combined with treatment standard (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v.) plus Midostaurin (recommended phase II dose, RP2D) in FLT3 mutated AML

Phase II Trial (MAGMA): treatment standard of FLT3 mutated AML (7+3 standard chemotherapy scheme using cytarabine 200 mg/m\^2 cont. inf. i.v. and daunorubicin 60 mg/m\^2 i.v plus midostaurin). No additional GO is given.

Midostaurin (IMP) induction: 25 mg or 50 mg peroral BID, days 8 to 21 depending on assigned dose level

GO (IMP) induction: 3 mg/m\^2 i.v. max 4.5 mg, on day1, or on days 1, 4, or days 1, 4, 7 depending on assigned dose level

Daunorubicin (DNR, non-IMP) induction: 60 mg/m\^2/day i.v., days 1 to 3

Cytarabine (AraC, non-IMP) induction: 200 mg/m\^2/day cont. infusion, days 1 to 7

MODULE: conventional chemotherapy (Cytarabine+Daunorubicin) in combination with midostaurin+GO

Midostaurin (IMP):

RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21 induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles;

GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg, RP2D, 1 induction cycle only

Daunorubicin (DNR, non-IMP):

60 mg/m\^2 i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders

Cytarabine (AraC, non-IMP):

200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

MAGNOLIA-trial: Midostaurin associated with conventional chemotherapy (AraC+DNR)+GO

GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg on days 1, 4, 7; 1 induction cycle only

Daunorubicin (DNR, non-IMP):

60 mg/m\^2/day i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders

Cytarabine (AraC, non-IMP):

200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

MAGNOLIA-trial: conventional chemotherapy (AraC+DNR)+GO

Midostaurin (IMP):

RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21, induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles;

GO (IMP): 3 mg/m\^2 i.v. max 4.5 mg, RP2D, 1 induction cycle only

Daunorubicin (DNR, non-IMP):

60 mg/m\^2/day i.v., days 1 to 3 of induction cycles 1-2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders

Cytarabine (AraC, non-IMP):

200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

MAGMA-trial:GO associated with conventional chemotherapy (AraC+DNR)+Midostaurin

Midostaurin (IMP):

RP2D peroral, days 8 to 21, induction cycle 1; 50 mg peroral BID, days 8 to 21 induction cycle 2; 50 mg peroral BID, days 8 to 21, 3 consolidation cycles; 50 mg peroral BID, days 1 to 28, 12 maintenance cycles

Daunorubicin (DNR, non-IMP):

60 mg/m\^2/day i.v., days 1 to 3 of induction cycle 1 and 2 in good and moderate responders; 50 mg/m\^2/day i.v., days 1 to 3 of induction cycle 2 in non-responders

Cytarabine (AraC, non-IMP):

200 mg/m\^2/day cont. infusion, days 1 to 7 of induction cycles 1 and 2 in good and moderate responders; 3000/1500 mg/m\^2/day i.v. BID, days 1 to 3 of induction cycle 2 in non-responders; 3000/1500 mg/m\^2 i.v. BID, days 1, 3, 5 of consolidation, 3 cycles

MAGMA-trial: conventional chemotherapy (AraC+DNR)+Midostaurin

Christoph Röllig, Prof. Dr.

Manja Reimann, Dr.

Veit Bücklein, Dr.

Maher Hanoun, PD Dr.

Edgar Jost, Prof.

Christoph Schmid, Prof.

Mathias Hänel, Prof.

Christoph Röllig, Prof.

Björn Steffen, Dr.

Christine Dierks, Prof.

Tim Sauer, Dr.

Sebastian Scholl, Prof. Dr.

Lars Fransecky, Dr.

Dirk Niemann, Dr.

Madlen Jentzsch, PD Dr.

Nadine Müller, Dr.

Kristina Sohlbach, Dr.

Alexander Höllein, Prof. Dr.

Christoph Schliemann, Prof.

Kerstin Schäfer-Eckart, Dr.

Nadia Maguire

Martin Kaufmann, Dr.

Markus Schaich, Prof. Dr.

This phase I/II clinical trial evaluates the safety and efficacy of the combined administration of midostaurin and gemtuzumab ozogamicin in the frame of first-line standard chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients displaying a cytogenetic aberration or fusion transcript in the core-binding factor (CBF) genes or FMS-like tyrosine Kinase 3 (FLT3) mutation.

Acute myeloid leukemia is a malignancy that is still fatal for the majority of patients. Besides age, the genetic configuration of AML blasts is one of the strongest prognostic factors. Patients with mutations in the core-binding factor (CBF) genes have the best prognosis, however a considerable proportion of 35-60% will eventually relapse. Mutation and overexpression of receptor tyrosinkinases (RTK) have been proposed as main reasons for relapse development or chemoresistance in CBF AMLs. RTKs like stem cell factor receptor (c-KIT) and FLT3 are of high clinical relevance as they mediate proliferation and differentiation of hematopoietic stem cells. There is evidence that c-Kit mutations and high levels of c-KIT in CBF-AML have adverse effects on survival endpoints indicating c-KIT as potential therapeutic target in this special AML population. Midostaurin can be considered a potent c-KIT inhibitor besides having multi-kinase inhibitory activity for several other kinases of documented or potential pathogenetic relevance for AML, most importantly mutated FLT3. The kinase inhibition ultimately leads to inhibition of proliferation, cell cycle arrest, and apoptosis. Previous studies with other c-KIT inhibitors such as dasatinib showed promising results with respect to survival end points in newly diagnosed CBF AML patients. Midostaurin is considered a more potent c-KIT inhibitor than dasatinib and may be able to potentiate the inhibitory effect on leukemic cell growth.

Another important therapeutical target in CBF AML is the sialic acid-binding immunoglobulin-like lectin (CD33) which is expressed on the majority of AML blasts. Gemtuzumab Ozogamicin (GO) is a therapeutic CD33 antibody linked to a strong cytostatic drug (calicheamicin) which causes apoptosis of cancer cells upon internalization. For the combination of GO and standard intensive chemotherapy, metaanalyses of randomized trials have shown that i) a low-dose fractionated administration results in the best tolerability, and ii) among AML subgroups, patients with CBF AML have the greatest benefit from GO in addition to standard therapy. Subgroup analyses within the ALFA-0701 (A Randomized Study of Gemtuzumab Ozogamicin With Daunorubicine and Cytarabine in Untreated Acute Myeloid Leukemia Aged of 50-70 Years Old) trial population showing beneficial effects of GO on overall survival, relapse-free survival and event-free survival in patients positive for FLT3 mutation as compared to those negative for FLT3 mutation. Subgroup analyses of the GO registration trial ALFA-0701 showed a significant clinical benefit of the patients displaying a mutation in the FLT3 gene compared to those without this mutation. In Addition, CBF AML patients with FLT3 mutations expressed particularly high levels of CD33 antigen and that CD33 antigen levels were positively correlated to the improved survival after GO treatment. Furthermore, recently published data of two paediatric populations with internal tandem mutation in the FLT3 gene showed reduced relapse rates in GO recipients compared to the control group only receiving standard chemotherapy. These results suggest that GO is a particularly beneficiary agent in FLT3 mutated patients who would currently receive midostaurin in addition to intensive chemotherapy as a standard of care. Hence, from a clinical point of view there is an unambiguous rationale supporting the combination of midostaurin and GO for treatment of AML in the two cytogenetic subgroups: CBF AML and FLT3 mutated AML.

GO has become the new treatment standard for patients with CBF AML. The hypothesized positive effect of midostaurin is likely but randomized proof is laking.

Midostaurin has become the new treatment standard for AML patients with mutations in the FLT3 gene. The positive effect of GO is shown in a post-hoc subgroup analysis of the ALFA-0701 trial, but prospective randomized proof is lacking.

Therefore, the proposed trial intends i) to explore and establish the safe combination of GO plus midostaurin (MODULE) and ii) to evaluate the effect of midostaurin versus no midostaurin added to standard AML chemotherapy plus GO in CBF AML (MAGNOLIA) and iii) to evaluate the effect of GO versus no GO added to standard AML chemotherapy plus midostaurin in FLT3 mutated AML (MAGMA).

The phase I dose escalation trial (MODULE) will be conducted according to the 3+3 design.

The phase II trial in CBF AML (MAGNOLIA) will be conducted in a open label and randomized manner.

The phase II trial in FLT3 mutated AML (MAGMA) will be conducted in a open label and randomized manner.

Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)

MidOStaurin + Gemtuzumab OzogAmIcin Combination in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)

as measured by the number of dose limiting toxicities related to midostaurin or GO exposure.

Time interval from date of randomization until either primary treatment failure or relapse or death, whichever occurs first.

CR/CRi rate is defined as the proportion of patients, who achieved a morphologic complete remission or a complete remission with incomplete hematologic recovery (CR or CRi) during study participation.

Duration of remission is defined as time interval from date of CR/CRi until morphologic relapse.

Cumulative incidence of relapse is defined as the time interval from date of first CR/CRi until relapse.

Relapse-free survival is defined as the time interval from date of first CR/CRi until either morphologic relapse or death in remission.

Overall survival is defined as time interval from date of randomization until death from any cause.

Early mortality is defined as death from any reason within 30 days and 60 days from start of induction.

Novartis Pharmaceuticals

Pfizer

Technische Universität Dresden

Symptoms and General Pathology

Glioma

Neoplasm Metastasis

Matthew White, MD

This study will compare the use of two contrast agents to analyze blood flow characteristics of brain tumors.

This study will compare contrast agents, gadobenate dimeglumine and gadobutrol, for MRI perfusion analysis in brain tumor patients.

Comparison of Contrast Agents for MRI Perfusion Analysis in Brain Tumor Patients

Gadobenate Dimeglumine Compared to Gadobutrol for MRI Perfusion Analysis in Brain Tumor Patients

Two contrast agents will be administered in different MRI imaging sessions. Will measure how the appearance of brain tumors change during dynamic first pass contrast administration.

Calculations will be made of cerebral blood volume, cerebral blood flow or ktrans in brain tumors when different contrast agents are administered. These parameters reflect vasculature and angiogenesis in tumors.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intraoperative Optical Imaging of Brain Function	NCT00632437	Brain Tumor	Speckle-Contras...	-	M.D. Anderson Cancer Center
Effect of SPGB on ICP and Oxygenation of Cerebral Venous Outflow in Craniotomy for Cerebral Tumors.	NCT04434651	Cerebral Tumor	SPGB	18 Years - 65 Years	Zagazig University
Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)	NCT04385290	Acute Myeloid L...	MODULE: convent... MAGNOLIA-trial:... MAGNOLIA-trial:... MAGMA-trial:GO ... MAGMA-trial: co...	18 Years - 75 Years	Technische Universität Dresden
Comparison of Contrast Agents for MRI Perfusion Analysis in Brain Tumor Patients	NCT02095353	Central Nervous...		19 Years -	University of Nebraska

Spots Global Cancer Trial Database for cbf

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

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