Neoplasms

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Musculoskeletal Diseases

Rare Diseases

Sarcoma

Recurrence

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Neoplasms, Connective Tissue

Neoplasms, Bone Tissue

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Bone Neoplasms

Osteosarcoma

Disease Attributes

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Connective Tissue Diseases

Bone Diseases

Soft Tissue Sarcoma

Ewing Sarcoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Vaccines

Temozolomide

Immunomodulating Agents

Camptothecin

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle).

1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Participants randomized to Group B were able to receive Vigil immunotherapy at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. Confirmation of progression by central radiologist and pre-approval from sponsor was required. 1 cycle = 21 days

Vigil is composed of autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional, short hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of the two TGβ isoforms.

Vigil

Injectable formulation of irinotecan was distributed from central supplier. 1 Cycle (5 doses of 50 mg/m2 per syringe) was drawn into provided oral syringes and dispenses to the subject with instructions to refrigerate until administration.

Dose: 100 mg/m2 daily, oral Schedule: Days 1-5, every 21 days Administered at least 1 hour before Irinotecan.

John Nemunaitis, MD

The goal of this clinical trial was to compare participants with first relapse or refractory Ewing's sarcoma when treated with investigational product (Vigil) in addition to the standard treatment of irinotecan and temozolomide compared to the standard treatment of irinotecan and temozolomide alone. The main question it aimed to answer is "Will participants who receive Vigil in addition to irinotecan and temozolomide have a prolonged time to progression and improved quality of life compared to the participants who receive irinotecan and temozolomide alone?".

This was a multicenter, Phase III study in participants with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory/intolerant or recurrent to 1 prior line of chemotherapy. Participants who agreed to participation had tumor tissue harvested from a scheduled standard surgical procedure (e.g., tumor biopsy or palliative resection). The tumor tissue removed was shipped to Gradalis, Inc. to attempt to manufacture the investigational product, Vigil.

Subjects who met eligibility criteria including manufacture of a minimum of 4 doses of Vigil were randomized 1:1 to either Group A (Vigil + Irinotecan + Temozolomide (Tem/Iri)) or Group B (Irinotecan + Temozolomide). Screening for the main portion of the study occurred as early as one week but no later than 8 weeks following tumor procurement.

Subjects received repeat cycles of treatment until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study. Subjects randomized to Group A (Vigil + Tem/Iri) received up to 12 doses depending upon the quantity of Vigil manufactured from the surgical specimen. 1 cycle = 21 days. If irinotecan + temozolomide was administered beyond 12 cycles, it was administered off study. Subjects randomized to Group B (Tem/Iri) may have crossed over to receive single agent Vigil every 21 days following End of Treatment assessment and documented disease progression confirmed by central radiology vendor, for up to 12 doses of Vigil depending upon the quantity of Vigil manufactured.

Participants were managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored. Blood for immune function analyses including IFNγ-ELISPOT analysis of cytotoxic T cell activation in response to autologous tumor antigens will be collected at tissue procurement, post-procurement screening and Day 1 (prior to chemotherapy administration) at Cycles 2, 4, and 6, end of treatment (EOT), 3 months after EOT, and every 6 months thereafter. Blood for ctDNA analysis was collected at tissue procurement, prior to chemotherapy administration at baseline and on Day 1 prior to chemotherapy administration at Cycles 2, 3, 4, and 6, and EOT. After progression, participants were contacted quarterly for documentation of post study therapies and survival status information.

Participants were randomized 1:1 to either Group A (Vigil + irinotecan and temozolomide) or Group B (irinotecan and temozolomide alone). Participants randomized to Group B were able to receive Vigil (Cross-Over) after confirmation of progression by central radiologist and sponsor approval.

A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide

A Multi-Center Phase III, Randomized, Open-Label Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Combination With Irinotecan and Temozolomide as a Second-Line Regimen for Ewing's Sarcoma

Progression Free Survival (PFS) is defined as the time from randomization to the event of disease recurrence/progression according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) for target lesions and assessed CT/MRI by local investigator.

OS is defined as time from randomization to death or to the date of last follow-up. The date of last follow-up confirming survival will be used as the censoring date for subjects who are alive and/or do not have a known date of death.

ORR is defined as the proportion of participants who have prolonged stable disease or a partial or complete response or complete response to therapy according to RECIST 1.1.

Participants were considered eligible for treatment, if the tissue submitted to Gradalis met all criteria, including manufacturing product release criteria.

Gradalis, Inc.

Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study.

Group A: Vigil in Combination With Irinotecan and Temozolomide

Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle).

1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study.

Group B: Irinotecan and Temozolomide

Participants assigned to Group B crossed-over to received Vigil monotherapy at a concentration of 1 X 10e6 cells//dose via intradermal injection every 21 days following End of Treatment assessment.

Participants received up to 12 doses of Vigil depending upon the quantity of Vigil manufactured.

Cross-over to Vigil Alone

Participants randomized to Group A received oral temozolomide 100 mg/m\^2 daily (Days 1-5), total dose 500 mg/m\^2/cycle) and oral irinotecan 50 mg/m\^2 daily (Days 1-5, total dose 250 mg/m\^2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Participants randomized to Group B received oral temozolomide 100 mg/m\^2 daily (Days 1-5), total dose 500 mg/m\^2/cycle) and oral irinotecan 50 mg/m\^2 daily (Days 1-5, total dose 250 mg/m\^2/cycle).

1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

An assessment of Performance Status (PS) on the Karnofsky or Lansky scale is standard way of measuring the ability of cancer patients to perform ordinary tasks. The PS scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities. The assessment is made by an investigator during the physical exam of the subject.

Baseline Performance Status

Only 1 subject randomized to Group B was eligible to Cross-over to receive Vigil.

Early termination of trial leading to small numbers of subjects analyzed. Technical problems with measurement leading to unreliable or uninterpretable data.

Clinical and Regulatory Operations

Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

PFS is not adequately assessable for difference between cohorts given only 5 participants were enrolled and received treatment.

Progression Free Survival (PFS)

OS is not adequately assessable for difference between cohorts given only 5 participants were enrolled and received treatment.

Overall Survival (OS)

No subjects on trial achieved a partial or complete response, therefore the ORR was not determined.

Overall Response Rate (ORR)

Participants who underwent tissue procurement and the processed tissue samples were successfully shipped to Gradalis whereby Vigil production was attempted.

Total Number of Tissue Procurements

All enrolled subjects who completed tissue procurement and the tissue was received by Gradalis for Vigil Manufacture. Any subjects whose tissue was not submitted to Gradalis was excluded in the analysis.

Vigil Manufacture Success Rate: Number of Participants Eligible for Treatment on the Main Study.

Main Study

Group B Crossover to Vigil Alone

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Shock

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Pharmaceutical Solutions

Bortezomib

Solution, IV, 340mg/m2, twice weekly for 2 weeks (3 week cycle), 60 minutes infusion

Tanespimycin

Solution, IV, 1.3 mg/m2, twice weekly for 2 weeks (3 weeks cycle), 3-5 minute bolus

Bristol-Myers Squibb

This is a phase 3, open label trial for patients with multiple myeloma in first relapse. Trial will compare tanespimycin (KOS-953), in combination with a fixed dose of bortezomib versus bortezomib alone.

Phase 3 combination study comparing tanespimycin (KOS-953) plus bortezomib to bortezomib alone in patients with multiple myeloma in first relapse after failure of previous anti-cancer therapy and/or bone marrow transplantation. Primary objective is to compare the progression-free survival (PFS) associated with the use of tanespimycin (KOS-953) in combination with bortezomib versus that associated with administration of bortezomib alone.

A Study of Tanespimycin (KOS-953) in Patients With Multiple Myeloma in First Relapse

Phase 3 Randomized, Open-Label Clinical Trial of Tanespimycin (KOS-953) Plus Bortezomib Compared to Bortezomib Alone in Patients With Multiple Myeloma in First Relapse

Study Director

Glioblastoma

Astrocytoma

Glioma

Anaplastic Astrocytoma

Elderly patients with IDH1R132H-non mutant and MGMT promoter-unmethylated anaplastic astrocytoma or glioblastoma who will receive TG02 and radiation therapy.

Elderly patients with IDH1R132H-non mutant and MGMT promoter-methylated anaplastic astrocytoma or glioblastoma who will receive TG02 and temozolomide.

Patients initially diagnosed with anaplastic astrocytoma or glioblastoma at first relapse post TMZ/RT --\> TMZ therapy who will receive TG02.

The initial cohorts of Groups A and B will receive TG02 at 200 mg on intermittent schedules in combination with either RT or TMZ. TG02 will be escalated to 250 mg if the dose decision criteria are met in the first cohort.

The initial cohort in Group C will receive TG02 alone at 250 mg on intermittent schedules. It will be continued at this dose if feasible or decreased to 200 or 150 mg if not tolerated.

TG02

For group A standard involved-field hypofractionated RT will be administered at 39.9 Gy in 15 fractions of 2.66 Gy for 3 weeks

Radiation Therapy

For group B TMZ will be given in the standard 28-day cycle regimen (150-200 mg/m2) for 5 days.

Emilie Le Rhun

This is a three parallel cohort, open-labeled, non-randomized, multicenter study. All three cohorts will enroll independently.

Group A will be composed of newly-diagnosed, elderly patients with IDH1R132H-non mutant and MGMT promoter-unmethylated anaplastic astrocytoma or glioblastoma who will receive TG02 and RT.

Group B will be composed of newly-diagnosed, elderly patients with IDH1R132H-non mutant and MGMT promoter-methylated anaplastic astrocytoma or glioblastoma who will receive TG02 and temozolomide.

For both Groups A and B, there will be a classical 3+3 dose escalation and an expansion phase in the study. Up to a total of 24 evaluable patients in Group A and up to a total of 12 evaluable patients in Group B (up to 36 evaluable patients for Groups A and B).

Group C patients will be composed of patients initially diagnosed with IDH1R132H-non-mutant anaplastic astrocytoma or glioblastoma at first relapse post TMZ/RT--\>TMZ therapy who will receive TG02.

Study of TG02 in Elderly Newly Diagnosed or Adult Relapsed Patients With Anaplastic Astrocytoma or Glioblastoma

Study of TG02 in Elderly Newly Diagnosed or Adult Relapsed Patients With Anaplastic Astrocytoma or Glioblastoma: A Phase Ib Study

Primary endpoints in Groups A and B are the determination of the Maximum Tolerated Dose (MTD) and the recommended phase II combination dose. This part is a two-cohort study of the combination of TG02 with hypofractionated RT in patients with tumors with an unmethylated MGMT promoter, or with TMZ in patients with tumors with a methylated MGMT promoter. Up to two dose levels of TG02 will be explored in each group.

Primary endpoint in Group C is Progression-free survival at 6 months (PFS-6) defined by RANO criteria.

Progression-free survival (PFS) defined by RANO criteria. For groups A and B progression-free survival at 6 months (PFS-6), for group all groups median progression-free survival.

For all groups median overall survival and OS at 9 months (OS-9), for group C additional overall survival at 1 year (OS-12).

For patients with measurable disease after debulking: best overall response distribution (BOR), objective response rate (PR+CR), complete response rate and duration of response (DOR).

For non-surgical patients or patients with surgery for recurrence, but measurable disease thereafter: best overall response distribution (BOR), objective (PR+CR) rate, complete response rate and duration of response (DOR)

For group C: neurological progression-free survival (NPFS) based on the Neurologic Assessment in Neuro-Oncology (NANO): median NPFS and NPFS at 6 months (NPFS-6).

This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting.

Correlation of molecular markers including MYC, MCL-1, CDK9 and CDK5 protein levels, and potentially others, with measures of clinical benefit.

Tragara Pharmaceuticals, Inc.

European Organisation for Research and Treatment of Cancer - EORTC

Disease Progression

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Daratumumab

Pomalidomide

Dexamethasone acetate

the first relapse of patients who received daratumumab, pomalidomide, and dexamethasone (Dara-PD) treatment

the first relapse of patients who received other regimens in the same period (including Dara-KPD, VPd, KPd, IPd, Pd) treatment

The investigators designed the present study with the aim of observing the efficacy and survival of D-Pd regimen compared with other regimens (including D-KPD,VPd, KPd, IPd, Pd) in the same period for the first relapse of MM patients receiving RVD regimen, so as to provide a safe and effective treatment strategy for the first relapse of MM patients.

To evaluate the impact of daratumumab, pomalidomide, and dexamethasone (Dara-PD) compared to other regimens in the same period (including Dara-KPD, VPd, KPd, IPd, Pd) on the second progression free survival time (PFS2) of first relapse of multiple myeloma. Among them, the second progression free survival time (PFS2) is defined as the time from enrollment to disease progression or death.

Dara-PD in the Treatment of Patients With First Relapse of Multiple Myeloma

Prospective, Multicenter, Open and Non-interference Observational Clinical Study of Daratumumab, Pomalidomide and Dexamethasone (Dara-PD) in the Treatment of Patients With First Relapse of Multiple Myeloma

daratumumab, pomalidomide, and dexamethasone (Dara-PD) compared to other regimens in the same period (including Dara-KPD, VPd, KPd, IPd, Pd) on the second progression free survival time (PFS2) of first relapse of multiple myeloma.

Evaluated according to the 2016 IMWG efficacy evaluation criteria, defined as the proportion of participants who achieved the best response as strict complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).

Evaluated according to the 2016 IMWG efficacy evaluation criteria, defined as the proportion of subjects who achieved the best response as strict complete response (sCR), complete response (CR), and very good partial response (VGPR).

MRD negative is defined as bone marrow MRD negative confirmed by new generation flow cytometry (NGF) or new generation sequencing technology (NGS) (the minimum detection sensitivity is that one clonal plasma cell can be detected from 105 nucleated cells);

Persistent MRD negative: new generation flow cytometry (NGF) or new generation sequencing technology (NGS) detects bone marrow MRD negative and imaging negative, with at least one year between two tests being negative

Overall survival (OS) evaluation: defined as the time from enrollment to death.

Evaluation of duration of remission (DOR): defined as the time from the first response to treatment to disease progression or death

Affiliated Hospital of Hebei University

Second Hospital of Shanxi Medical University

Shandong Cancer Hospital and Institute

First Affiliated Hospital of Jinan University

Sun Yat-sen University

FengYan Jin

Clinical Professor of Hematology Department

Anti-Infective Agents

Bendamustine Hydrochloride

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Bendamustine : 70 mg/m2 iv on D1 and 8, for each cycle Velcade : 1.3 mg/m2 iv on D1, 8, 15 and 22, for each cycle Dexamethasone : 20 mg/day po on D1, 8, 15 and 22, given prior to Bendamustine and Velcade

Bendamustine, Velcade and Dexamethasone

Philippe RODON, Doctor

Cyrille HULIN, Doctor

Jean-Luc HAROUSSEAU, Professor

Claire MATHIOT, Doctor

Marie-Odile PETILLON, Doctor

The present trial is designed as a phase II study that aims at estimating the efficacy of the combination of bendamustine, bortezomib and dexamethasone in relapsed/refractory multiple myeloma (MM). The response rate, i.e. the rate of the patients achieving a Complete Response or Partial Response at cycle 4, divided by the total intent to treat patient number is chosen as primary efficacy endpoint.

The estimation of the efficacy rate is to be based on an explorative pilot study, since immediate embarking on a large-scale comparative efficacy trial would not be acceptable from the point of view of resources. Moreover, this would induce ethical objections, as it does not seem to be justifiable to expose a large number of patients to an experimental approach without sufficient exploratory indications of an improved risk-benefit ratio.

After relapse or after early progression on first-line treatment, the prognosis of multiple myeloma (MM) patients is unfavourable, and the search for new treatment regimens, including drugs with novel mechanisms of action is essential.

Bendamustine and bortezomib have shown high activity boch in first-line regimens and pre-treated patients. The novel mechanism of action of the proteasome inhibitor and the non-cross resistance of bendamustine to other alkylating agents established in the first-line treatment of multiple myeloma seem to recommend a combination of the two drugs for salvage therapy (second-line regimen). Finally, the promising response data in a series of relapsing MM patients treated with bendamustine, bortezomib and prednisone support this assumption, as well as the feasibility and tolerability of the combination.

In summary, there is some evidence for a favorable risk/benefit ratio for the combination of bendamustine, bortezomib and a corticoid drug, warranting the exploration in a larger, prospectively designed multicenter phase II study.

Study of Bendamustine, Velcade and Dexamethasone in the Treatment of Elderly Patients With Multiple Myeloma

A Phase II Study of Bendamustine, Velcade and Dexamethasone (BVD) in the Treatment of Elderly Patients (>= 65 Years) With Multiple Myeloma in 1st Relapse or Refractory to 1st Line Therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide	NCT03495921	Ewing Sarcoma Ewing Family of... Ewing's Tumor M... Ewing's Sarcoma... Ewing's Tumor R... Rare Diseases Sarcoma Neoplasms, Conn... Neoplasms by Hi... Neoplasms, Bone... Neoplasms, Conn... Sarcoma, Ewing Neoplasms	Vigil Irinotecan Temozolomide	2 Years -	Gradalis, Inc.
A Study of Tanespimycin (KOS-953) in Patients With Multiple Myeloma in First Relapse	NCT00546780	Multiple Myelom...	Tanespimycin Bortezomib	18 Years -	Bristol-Myers Squibb
Study of TG02 in Elderly Newly Diagnosed or Adult Relapsed Patients With Anaplastic Astrocytoma or Glioblastoma	NCT03224104	Astrocytoma, Gr... Glioblastoma	TG02 Radiation Thera... Temozolomide	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Study of TG02 in Elderly Newly Diagnosed or Adult Relapsed Patients With Anaplastic Astrocytoma or Glioblastoma	NCT03224104	Astrocytoma, Gr... Glioblastoma	TG02 Radiation Thera... Temozolomide	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Study of TG02 in Elderly Newly Diagnosed or Adult Relapsed Patients With Anaplastic Astrocytoma or Glioblastoma	NCT03224104	Astrocytoma, Gr... Glioblastoma	TG02 Radiation Thera... Temozolomide	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Dara-PD in the Treatment of Patients With First Relapse of Multiple Myeloma	NCT06252792	Multiple Myelom... First Relapse		18 Years -	The First Hospital of Jilin University
Study of Bendamustine, Velcade and Dexamethasone in the Treatment of Elderly Patients With Multiple Myeloma	NCT01045681	Multiple Myelom...	Bendamustine, V...	65 Years -	Intergroupe Francophone du Myelome
Dara-PD in the Treatment of Patients With First Relapse of Multiple Myeloma	NCT06252792	Multiple Myelom... First Relapse		18 Years -	The First Hospital of Jilin University

Spots Global Cancer Trial Database for first relapse