Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Lung Neoplasms

Vascular Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Prostatic Neoplasms

Breast Neoplasms

Colorectal Neoplasms

Recurrence

Lymphoma

Leukemia

Thrombosis

Hemostatic Disorders

Blood Coagulation Disorders

Body Weight

Gastrointestinal Neoplasms

Intestinal Neoplasms

Lymphoproliferative Disorders

Myeloproliferative Disorders

Thromboembolism

Venous Thromboembolism

Venous Thrombosis

Urogenital Neoplasms

Digestive System Neoplasms

Lymphatic Diseases

Embolism

Embolism and Thrombosis

Lymphosarcoma

Chronic Myeloproliferative Disorders

Fibrinolytic Agents

Anticoagulants

All Drugs and Chemicals

Coagulants

Heparin

Hemostatics

Calcium heparin

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

Patients with objectively confirmed cancer associated venous thromboembolism receiving tinzaparin treatment to prevent recurrence of venous thromboembolism

Subcutaneous injection of 175 IU/kg once daily for 6 months

G Meyer, Professor

F Scotte, Dr

The purpose of this study is to validate the Ottawa score (risk of thromboembolic recurrences) in cancer patients with thromboembolic disease treated with tinzaparin (Innohep®)

The Ottawa score is a clinical predictive score aiming at stratifying thromboembolic recurrences in cancer patients according to identified clinical risk factors and histological type of the tumor. This score has never been validated externally in a prospective way in patients treated with tinzaparin. The objective of this observational prospective study is to enroll cancer patients with TED treated with tinzaparin for a planned period of 6 months and to collect data on thromboembolic recurrences, major hemorrhages, deaths and heparin-induced thrombocytopenia

Non Interventional Study of the Validation of the Ottawa Score in Cancer Patients With Venous Thromboembolism (VTE)

Prediction of Thromboembolic Recurrences in Cancer Patients With Venous Thromboembolic Disease (TED)

LEO Pharma

Lymphocele

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Cysts

PerFix involves suturing the free end of the peritoneal flap left after RARP + ePLND to the pelvic wall near the symphysis of the pubic bones leaving two lateral openings for directing the lymphatic fluid out of the pelvis to the abdominal cavity.

Peritoneal fixation (PerFix)

Standard of care

Vladimir Student, MD, PhD

The PerFix Trial aims to compare the use of peritoneal fixation technique to standard of care (no fixation) during robot-assisted radical prostatectomy with extended pelvic lymph node dissection (RARP + eLND) for the prevention of symptomatic and radiologic lymphocele formation.

Extended pelvic lymph node dissection (ePLND) is the most accurate staging tool to determine lymph node involvement in prostate cancer. As urologist perform this procedure more often now, thanks to the shift to more advanced and aggressive stages, the role of ePLND is expanding. The main complication of PLND is development of a collection of lymphatic fluid called a lymphocele. Lymphoceles can be associated with abdominal pain, lower urinary tract symptoms, bladder outlet obstruction, penile or scrotal edema, infection/sepsis, lower extremity swelling and deep vein thrombosis. They necessitate intervention in up to 10% of patients treated with RARP + ePLND which includes drainage or surgery. Radiologic incidence can be as high as around 50% of operated patients with unknown clinical relevance. Many interventions aimed at reducing the rate of lymphocele formation with limited success so far. Several retrospective studies suggested using peritoneal flap fixation technique which could direct the lymphatic fluid to the peritoneal cavity out of the pelvis and its ensure its reabsorption there. We hypothesize that peritoneal fixation can potentially lower the incidence of symptomatic and radiologic lymphocele formation. By preventing this potentially very dangerous complication, it could be very beneficial for a large group of patients suffering from aggressive localized prostate cancer who are scheduled for RARP + ePLND.

Our goal is to is to test this hypothesis in a randomized trial comparing the fixation technique to standard of care, i.e. no fixation.

Effect of Peritoneal Fixation on Lymphocele Formation

Prospective Randomized Trial Evaluating the Effect of Peritoneal Flap Fixation on Symptomatic and Radiologic Lymphocele Formation Following Robot Assisted Radical Prostatectomy With Extended Pelvic Lymph Node Dissection (PerFix)

The number of participants with symptomatic lymphocele will be determined. Clinical symptoms, time of onset, the size of the lymphocele, location, number of Lymphoceles and intervention needed will be measured

The number of participants with radiologic lymphocele on Pelvic CT scan will be determined together with the size, location and number of detected lymphoceles.

Incidence of adverse events in the Prefix group compared to control group (no PerFix) will be measured. Surgical complications will be evaluated according to Clavien-Dindo classification

The change in lymphocele size during follow-up CT scan will be examined

Radiologic investigation will be done in case of by swelling or pain of the lower extremity and the number of any venous thromboembolism will be determined

Perioperative outcomes (time of the surgery, blood loss and hospital stay) will be measured

The rate of continent patients will be defined using pads needed per day. Continent equals to 0-1 pad per day.

Potency equals to 19 and more points in the International index of erectile function (IIEF5) questionnaire (scale 0-25), the higher the score, the better.

Change in the International prostate symptom score (IPSS) questionnaire from the baseline will be assessed (scale 0-35, higher score means worse outcome).

University Hospital Olomouc

Vladimir Student Jr., MD, PhD, FEBU

Leukemia, Lymphoid

Lymphoma, Non-Hodgkin

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Hodgkin Disease

Lymphoma, B-Cell

Immunoproliferative Disorders

Neoplasms by Histologic Type

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

B-cell Lymphoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

Hodgkin Lymphoma

Antineoplastic Agents

Antirheumatic Agents

Amino Acids

Atezolizumab

Antibodies

Bendamustine Hydrochloride

Rituximab

Durvalumab

Lenalidomide

Immunoglobulins

Ibrutinib

Antineoplastic Agents, Immunological

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants assigned to Arm A will receive:

* Durvalumab 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and
* Lenalidomide orally at assigned dose levels (10 mg, 15 mg or 20 mg) once daily on Days 1 to 21 of:

  * Cycles 1 through 13 in indolent non-Hodgkin's lymphoma (NHL) or
  * All cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL
* Rituximab 375 mg/m² IV infusion every week in Cycle 1 (Days 2, 8, 15, 22) and on Day 1 of Cycles 2 through 5.

All treatment cycles were 28 days.

Participants assigned to Arm B will receive:

* Durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13
* Ibrutinib orally at assigned dose levels (280 mg, 420 mg, or 560 mg) once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

All treatment cycles were 28 days.

Participants assigned to Arm C will receive:

* Durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13
* Rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose will be 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose)
* Bendamustine IV infusion at assigned dose levels (70 mg/m² or 90 mg/m²) on Days 1 and 2 of Cycles 1 through 6.

All treatment cycles were 28 days.

Participants assigned to Arm D will receive durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13. All treatment cycles were 28 days.

Administered as an IV infusion (250 mL) over approximately 1 hour in duration

Administered as a 30-minute intravenous infusion

Bendamustine

Bristol-Myers Squibb

This study is designed to determine the recommended phase 2 dose (RP2D), and the safety, and efficacy of durvalumab as monotherapy and when given in combination with lenalidomide and rituximab; ibrutinib; or bendamustine and rituximab at the RP2D in adults with lymphoma or chronic lymphocytic leukemia (CLL).

The study was to consist of 3 parts: dose-finding, dose-confirmation, and dose-expansion. In this study, 4 treatment arms were to be investigated:

* Arm A: durvalumab and lenalidomide ± rituximab
* Arm B: durvalumab and ibrutinib
* Arm C: durvalumab and rituximab ± bendamustine
* Arm D: durvalumab (monotherapy)

The study was to start with 3 dose-finding cohorts (Arms A, B, and C) and 1 dose-confirmation cohort (Arm D) in parallel. All treatment arms were to be open for enrollment at study start except in the US, where Arm D was to enroll depending on the availability of treatment slots and following the completion of assessment of responses from the combination therapy arms. For Arms A and C, prior to enrolling participants to receive all 3 drugs, the doublet combinations were to be evaluated. Once the doublet combinations were deemed tolerable, the eventual triplet combinations were to be tested.

On 05 September 2017, the US FDA issued a Partial Clinical Hold on the study Arm A. Following this Partial Clinical Hold no more participants were enrolled into study Arm A. Participants already enrolled and treated in Arm A who were receiving clinical benefit, based on the discretion of the investigator, could continue study treatment after being reconsented. Arm B and C completed dose confirmation. The dose expansion part of the study was not opened.

Within Arms A, B, and C participants on the dose-finding part were enrolled sequentially according to a 3+3 design. All treatment arms were to be open for enrollment at study start except in the US, where Arm D was to enroll depending on the availability of treatment slots and following the completion of assessment of responses from the combination therapy arms.

A Study to Determine Dose, Safety, and Efficacy of Durvalumab as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocytic Leukemia

A Phase 1/2, Open-label, Multi-center Study to Assess the Safety and Tolerability of Durvalumab (Anti-PDL1 Antibody) as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocitic Leukemia

Dose limiting toxicities were evaluated during the DLT evaluation period for participants in the dose finding cohorts. The severity grading was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT is defined as below: Hematologic DLT • Grade 4 neutropenia observed for greater than 5 days duration • Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration • Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement for platelets transfusion • Grade 4 anemia, unexplained by underlying disease • Any other grade 4 hematologic toxicity that does not resolve to participant's pretreatment baseline level within 72 hours. Non-Hematologic DLT • Any non-hematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by medical management • Any treatment interruption greater than 2 weeks due to adverse event.

Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) occurring or worsening on or after the first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. The intensity of AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by the investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5).

For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percent of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL).

For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification) (Cheson, 2014). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percentage of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL).

Time to response was calculated as the time from first dose of study drug to the first response date (CR or PR for lymphoma participants and CR, CRi, nPR, PR, or PRL for CLL participants).

Duration of response is defined for responders only as the time from the first documented response (CR or PR for lymphoma participants or CR, CRi, nPR, PR, or PRL for CLL participants) to disease progression or death (from any cause). For participants with response but no progression, or death, duration of response was censored at the last date that the participant was known to be progression-free.

Progression-free survival was calculated as the time from first dose of study drug to the first documented progression or death (from any cause) during the entire efficacy evaluation period. For participants with no progression or death, PFS was censored at the last assessment date the participant was known to be progression-free.

Change from baseline in sPD-L1 could not be calculated as all post-baseline samples were below the lower limit of quantification (\<15.60 pg/mL).

Celgene

Participants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.

Part 1, Arm A: DUR 1500 mg + LEN 20 mg

Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab (RIT) 375 mg/m² IV infusion on Days 2, 8, 15, and 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.

Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²

Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.

Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib (IBR) 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

Part 1, Arm B: DUR 1500 mg + IBR 420 mg

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

Part 1, Arm B: DUR 1500 mg + IBR 560 mg

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m²

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²

Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg

Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg

Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.

Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²

Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.

Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²

Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²

Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Part 2, Arm D FL: DUR 1500 mg

Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Part 2, Arm D DLBCL: DUR 1500 mg

Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Part 2, Arm D CLL/SLL: DUR 1500 mg

Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Part 2, Arm D MCL: DUR 1500 mg

Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Part 2, Arm D HL: DUR 1500 mg

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Histology

ECOG performance status is used to describe a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 to 5: • 0 = Fully active, no restrictions; • 1 = Restricted activity but ambulatory, able to carry out work of a light nature; • 2 = Ambulatory and capable of all self-care but unable to carry out work activities; • 3 = Limited self-care, confined to bed or chair more than 50% of waking hours; • 4 = Completely disabled, no selfcare, confined to bed or chair; • 5 = Dead

Eastern Cooperative Oncology Group ECOG) Performance Status

The study was placed on full clinical hold by the United States (US) Food and Drug Administration (FDA) on 05 Sep 2017. As the result, the study was closed for further enrollment, and all participants were discontinued from all study treatments (durvalumab, lenalidomide and dexamethasone). All participants were followed for second primary malignancies (SPMs) for 5 years after the last participant has been enrolled as per protocol.

Bristol-Myers Squibb Study Director

The safety review committee identified a preliminary recommended Phase 2 dose (RP2D) for each dose finding cohort based on an integrated assessment of the safety, pharmacokinetic, pharmacodynamic, and preliminary efficacy (as available).

For Arm B, ibrutinib 420 mg was confirmed as the RP2D for CLL/SLL participants and ibrutinib 560 mg was confirmed as the RP2D for MCL participants.

For Arm C the RP2D was confirmed as rituximab 375 mg/m² + bendamustine 70 mg/m².

DLT Evaluable population included participants in Arms A, B, and C of Part 1, who took at least one dose of study drug and completed the DLT evaluation through the end of DLT evaluation period, or participants who took at least one dose of study drug and experienced at least one DLT prior to completion of the DLT evaluation period.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Non Interventional Study of the Validation of the Ottawa Score in Cancer Patients With Venous Thromboembolism (VTE)	NCT03099031	Venous Thromboe...	Tinzaparin	18 Years -	LEO Pharma
Effect of Peritoneal Fixation on Lymphocele Formation	NCT04853095	Prostate Cancer Lymphocele Afte...	Peritoneal fixa... Standard of car...	18 Years -	University Hospital Olomouc
A Study to Determine Dose, Safety, and Efficacy of Durvalumab as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocytic Leukemia	NCT02733042	Lymphoma Leukemia, Lymph...	Durvalumab Lenalidomide Rituximab Ibrutinib Bendamustine	18 Years -	Celgene
Effect of Peritoneal Fixation on Lymphocele Formation	NCT04853095	Prostate Cancer Lymphocele Afte...	Peritoneal fixa... Standard of car...	18 Years -	University Hospital Olomouc

Spots Global Cancer Trial Database for lymphatic disease