Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Case Report forms, Quality of life questionaire

Assesment of Effectiveness and side effects

Laila König, MD

Adriane Hommertgen, Phd

Juergen Debus, Professor

The aim is to record and document a mediastinal PT and the corresponding follow-up data (effectiveness and side effects). General recommendations for planning and feasibility are made within the framework of this study.

Improvements in multimodal therapy have resulted in high curation rates in lymphoma patients. In addition, these cancer entities (Hodgkin lymphoma and non-Hodgkin lymphoma) often affect very young patients. Due to the high healing rates, the long-term effects of therapy are increasingly coming into focus: more than 40% of patients suffer from chronic, therapy-associated secondary diseases 30 years after successful therapy \[1\]. For this reason, an important focus of current research is the reduction of therapy-associated toxicity. A certain trend of dose reduction and reduction of the radiation fields (involved-field, involved-node, involved-site radiation) can already be seen in the research results of the last decades. Another interesting approach to protecting adjacent organs is the use of modern radiation techniques such as particle therapy with protons (PT).

In the case of radiation in the mediastinal area in particular, the use of PT can greatly reduce the dose in the area of the heart muscle, the lungs or the mammary gland tissue compared to conventional radiation with photons. It is hoped that this will result in a decrease, especially in chronic side effects, in the area of these organs. Since this is a group of young patients with intensive pre-treatment with chemotherapeutic agents, a reduction in long-term toxicities is of particular importance. In particular, cardiac and pulmonary long-term side effects as well as a reduction in the secondary malignancy rate play a major role in this collective.

The aim of this prospective registry study on proton radiotherapy for mediastinal lymphomas is to record the frequency, feasibility and side effects after PT in this group of patients. These data should then serve as the basis for concrete therapy recommendations and assessment of side effects. Close cooperation with the study groups should also enable a comparative analysis of comparable patients who were not treated with protons at a later point in time.

Registry Study of Proton Radiotherapy in Lymphoma

Multicenter Registry Study on Proton Radiotherapy for Mediastinal Lymphomas

Effectiveness and side effects of proton radiotherapy

University Hospital Heidelberg

Head of Department

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

B-cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Brentuximab Vedotin

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

This is a single-arm, open-label, multicenter, Phase 2 clinical trial to evaluate the efficacy and safety of Brentuximab vedotin as a single agent in patients with relapsed or refractory PMLBCL who have previously received a first line of treatment with chemotherapy or immunotherapy.20 patients will be treated in this study and All patients will receive 1.8 mg/kg Brentuximab vedotin administered as a single outpatient IV infusion on Day 1 of each 21-day treatment cycle. Patients may continue on study treatment until disease progression or unacceptable toxicity. Patients who achieve stable disease or better as assessed by investigator should receive a minimum of 8, but no more than 16 cycles of study treatment.

Brentuximab vedotin, 1.8 mg/kg, administered via outpatient IV infusion on Day 1 of each 21-day cycle.

Pier Luigi Zinzani, Prof.

Study Objectives Primary:

• To determine the antitumor efficacy of single-agent Brentuximab vedotin (1.8 mg/kg administered intravenously every 3 weeks) as measured by the overall objective response rate in patients with relapsed or refractory primary mediastinal large B-cell lymphoma.

Secondary:

* To assess duration of tumor control, including duration of response and progression-free survival
* To assess survival
* To assess the safety and tolerability of Brentuximab vedotin

Additional:

• To assess disease-related symptoms

Number of Planned Patients 20 patients will be enrolled in this study. Duration of the study The study duration is 18 months for enrollment and 2 years for the follow-up.

Study Population Eligible patients are those with relapsed or refractory primary mediastinal large B-cell lymphoma. Patients must also have histologically-confirmed CD30-positive disease, fluorodeoxyglucose (FDG)-avid and measurable disease of at least 1.5 cm, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate hematologic, kidney, and liver function.

Eligible patients must not previously have been treated with Brentuximab vedotin or previously received an allotransplant. In addition, patients must not have congestive heart failure, known cerebral/meningeal disease, or any active viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 2 weeks prior to first study dose.

Study Design This is a single-arm, open-label, multicenter, clinical trial to evaluate the efficacy and safety of Brentuximab vedotin as a single agent in patients with relapsed or refractory primary mediastinal large B-cell lymphoma.

Brentuximab vedotin will be administered as a single IV infusion on Day 1 of each 21-day cycle. Measures of anti-cancer activity will be assessed using the revised response criteria for malignant lymphoma. CT scans (chest, neck, abdomen, and pelvis) will be performed at baseline and Cycles 2, 4, 7, 10, 13, and 16 and PET scans will be done at baseline and Cycles 4 and 7. Patients will have an EOT assessment 30 ± 7 days after receiving their final dose of study drug. Long-term follow-up assessments (including survival and disease status information) will be performed every 12 weeks until either patient death or study closure, whichever occurs first. Patients who discontinue study treatment with stable disease or better will have CT scans done every 12 weeks until disease progression.

Test Product, Dose, and Mode of Administration Brentuximab vedotin, 1.8 mg/kg, administered via outpatient IV infusion on Day 1 of each 21-day cycle.

Number of Planned Patients 20 patients will be enrolled in this study. Duration of Treatment Brentuximab vedotin will be administered as a single IV infusion on Day 1 of each 21-day cycle. Patients may continue on study treatment until disease progression or unacceptable toxicity. Patients who achieve stable disease or better should receive a minimum of 8, but no more than 16 cycles of study treatment.

Duration of the study The study duration is 18 months for enrollment and 2 years for the follow-up. Efficacy Assessments Treatment response will be assessed by tumor imaging (spiral CT of neck, chest, abdomen, pelvis and PET scans) performed at protocol-specified timepoints. Determination of antitumor efficacy will be based on objective response assessments made according to the Revised Response Criteria for Malignant Lymphoma. Clinical response of progressive disease (PD), stable disease (SD), partial remission (PR), or complete remission (CR) will be determined at each assessment. Responses will be determined by investigator.

Safety Assessments Assessment of safety during the course of this study will consist of the surveillance and recording of adverse events (AEs), recording of concomitant medication and measurements of protocol-specified physical examination findings and laboratory tests.

A Study of SGN-35 (Brentuximab Vedotin) of Patients With Relapsed or Refractory PMLBCL

A Phase II Study of SGN-35 (Brentuximab Vedotin) of Patients With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (PMLBCL)

The antitumor efficacy of single-agent Brentuximab vedotin (1.8 mg/kg administered intravenously every 3 weeks) as measured by the overall objective response rate in patients with relapsed or refractory primary mediastinal large B-cell lymphoma was determined using Cheson BD, Pfistner B, Juweid ME, et al. "Revised response criteria for malignant lymphoma". J Clin Oncol. 2007 Feb 10;25(5):579-586.Treatment response was assessed by dedicated spiral CT scan of neck, chest, neck, abdomen, and pelvis and PET scans performed at protocol-specified time points. Clinical response of progressive disease (PD), stable disease (SD), partial remission (PR), or complete remission (CR) will be determined at each assessment.

Fondazione Italiana Linfomi - ETS

We used the Common Terminology Criteria for Adverse Events v. 4.0 (CTCAE) for the coding of adverse events.

This is a single-arm, open-label, multicenter, Phase 2 clinical trial to evaluate the efficacy and safety of Brentuximab vedotin as a single agent in patients with relapsed or refractory PMLBCL who have previously received a first line of treatment with chemotherapy or immunotherapy.20 patients will be treated in this study and All patients will receive 1.8 mg/kg Brentuximab vedotin administered as a single outpatient IV infusion on Day 1 of each 21-day treatment cycle. Patients may continue on study treatment until disease progression or unacceptable toxicity. Patients who achieve stable disease or better as assessed by investigator should receive a minimum of 8, but no more than 16 cycles of study treatment.

Brentuximab Vedotin: Brentuximab vedotin, 1.8 mg/kg, administered via outpatient IV infusion on Day 1 of each 21-day cycle.

Vial for IV Infusion

Age, Categorical

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Italy

Region of Enrollment

MD Vittorio Stefoni

Quick PD

PD after 1 cycle

PD after 2 cycle

SAE not related to drug

Trial was closed due to drug inefficacy on 14/Jul/2016 (last enrollment on 30/Jun/2015). Details in the Outcome Measure Data Table.

Overall Objective Response Rate in Patients With Relapsed or Refractory PMLBCL

Overall Study

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Cardiotoxicity

Hodgkin Disease

Hodgkin Lymphoma

Patients whose radiation therapy field essentially encompasses anterior mediastinum; namely, the majority of malignant lymphoma patients with mediastinal involvement.

As for consolidative RT used in patients with early-stage Hodgkin lymphoma, the RT field must essentially include the mediastinum.

Standard treatment protocol with combined chemoradiation

Shinn-Yn Lin, M.D.

Malignant anterior mediastinal tumors essentially include lymphomas and thymomas. The location of mediastinum is anatomically close to several critical organs such as heart, lung, and breasts, which might be affected meaningfully when the mediastinal region is irradiated. There have been quite a few studies investigating long-term toxicities concerning the above critical organs and risks of secondary malignancies related to treatment regimens combining chemotherapy and mediastinal radiotherapy. With the advancement of modern radiotherapy, highly conformal and intensity modulated radiotherapy have become a radiotherapeutic standard in recent years. However, most previous studies analyzed patients treated in the era of 2D techniques rather than conformal 3D plans. Almost inevitably, a large volume of the heart and lung was irradiated via the 2D technique with which substantial dose levels might be given to these organs unavoidably. Certainly long-term radiotherapy related toxicities are significantly associated with the dose and volume irradiating the normal organs at risk. Relying on the techniques of modern conformal radiotherapy and the contemporary strategy of multimodality therapy, the dose and volume irradiating the heart and lung were considerably reduced. Therefore, objective tools including heart echocardiography and lung function test will be utilized in this prospective study to evaluate and monitor mainly the patients diagnosed as malignant lymphoma who are recommended to receive mediastinal radiotherapy in the era of modern treatment strategy and techniques.

The participants potentially included in the current study are mainly lymphoma patients with mediastinal malignant lymphoma or patients whose radiation therapy field essentially encompasses anterior mediastinum. Patients are prospectively enrolled in this study after physicians' clinical judgement. After signing the consent form, the recruited patient will receive comprehensive pre-radiotherapy evaluations, including cardiac echocardiography, laboratory tests (BNP, and NT-pro BNP), and lung function tests. Participants who are particularly female patients under the age of 45 will receive pre-radiotherapy breast echocardiography. Radiotherapy treatment planning of both photon and proton respectively will be simulated on Eclipse® treatment planning system. Subsequently participants will receive mediastinal RT within one month after being enrolled in the study. Eligible patients should receive standard multidisciplinary treatment as the tumor board at our institute has suggested. Modern radiotherapy techniques comprise all available modalities in our hospital, including photon or proton beams, intensity-modulated radiotherapy, volumetric modulated arc therapy, image-guidance, and breathing control system. The prescription of treatment field designing and dose scheme will comply with our institutional protocols and updated cancer treatment guidelines. Participants will receive longitudinal follow-up examinations at 3, 6, 9, 12, 18, 24, 36 months after the start of RT course. Standardized examinations include the above mentioned cardiac echocardiography and relevant tests.

It is anticipated that long-term mediastinal RT-related late effects are prospectively and longitudinally surveyed through consistent heart examinations and lung function tests. Long-term effects are expected to be lower with using maturely and widely adopted modern RT techniques. Therapeutic and survival outcomes are expected to be satisfactory, achieving the international level in this prospective observational study focusing on mainly lymphoma patients with mediastinal involvement who are suggested and scheduled to receive mediastinal RT as part of the combined modality treatment.

This study aims to standardize the application of clinical examinations including cardiac echocardiography, lung function tests, and relevant laboratory tests as part of objective tools for monitoring patients' cardiac and pulmonary functions after receiving mediastinal RT. Therefore, it is expected that the risk factors of predisposing patients to develop cardiac toxicities after chemoradiation particularly including mediastinal RT will be explored and identified. In addition objectivity of BNP (or NT-pro BNP) will also be verified in combination with the objective measurement and findings obtained from cardiac echocardiography. It is anticipated that our study would be an important and leading one that integrates radiation oncology, hematology, cardiology, and pulmonology into prospective and longitudinal cardiopulmonary surveillance carried out for mainly malignant lymphoma patients undergoing mediastinal RT in this era of modern chemoradiation.

Lymphoma Patients Undergoing Mediastinal Radiotherapy in the Era of Modern Chemoradiation

A Prospective Observational Study With Longitudinal Cardiopulmonary Surveillance in Lymphoma Patients Undergoing Mediastinal Radiotherapy in the Era of Modern Chemoradiation

The outcome assessed by cardiac echocardiography. Our study use the standard imaging modality -cardiac echocardiography

The outcome assessed by plasma concentrations of BNP and NT-proBNP

The outcome assessed by lung function test. The lung function tests contain following four tests: "Determination of F. R. C" \& "Diffusion capacity rate" \& "Screening sporometry before \& after B. D." and "Simple bronchodilator test".

The outcomes assessed by echocardiography

Overall survival time, indicated by the time from the date of recruitment to the date of expiring

Chang Gung Memorial Hospital

Infections

Recurrence

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Burkitt Lymphoma

Waldenstrom Macroglobulinemia

Disease Attributes

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Mantle Cell Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Amino Acids

Antibodies

Pembrolizumab

Immunoglobulins

Ibrutinib

Immune Checkpoint Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Laboratory Biomarker Analysis

Kami Maddocks, MD

This phase I/Ib trial studies the side effects and best dose of ibrutinib when given together with pembrolizumab and to see how well they work in treating patients with non-Hodgkin lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Given pembrolizumab and ibrutinib may work better in treating patients with non-Hodgkin lymphoma.

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory non-Hodgkin lymphoma (NHL).

II. To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

III. To evaluate the efficacy of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR), duration of response, progression-free survival and overall survival of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

TERTIARY OBJECTIVES:

I. To explore the relationship between prognostic parameters including ki-67 staining, PD-1 staining and cell of origin (activated B-cell or ABC versus germinal center B-cell or GCB) with ORR to the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

II. To determine relationship between gene mutations and resistance to therapy with the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL (BTK, PLC gamma 2, PD-1).

III. To evaluate and monitor effects on B-, T-, and natural killer (NK)-cell function with the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

OUTLINE: This is a phase I, dose-escalation study of ibrutinib followed by a phase Ib study.

Patients receive ibrutinib orally (PO) daily on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days, and then every 3 months for 2 years and every 6 months for 3 years.

Pembrolizumab and Ibrutinib in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

A Phase I/Ib Study of the PD-1 Antibody Pembrolizumab in Combination With Ibrutinib in Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL)

Baseline levels in these markers will be explored in relation to clinical outcome using graphical analyses as well as summarized quantitatively. Will utilize different plotting characters and colors for successes vs. not in the graphical analyses to help identify potential patters, and summarize the changes quantitatively between successes vs not.

Baseline levels in these markers will be explored in relation to clinical outcome using graphical analyses as well as summarized quantitatively. Will utilize different plotting characters and colors for successes versus (vs.) not in the graphical analyses to help identify potential patters, and summarize the changes quantitatively between successes vs not.

Summarized based on severity and perceived attribution to study treatment. Will be assessed and tabulated by dose level.

Will be evaluated for each of the cohorts and graphically summarized using the methods of Kaplan and Meier.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Registry Study of Proton Radiotherapy in Lymphoma	NCT04613388	Mediastinal Lym...	Assesment of Ef...	18 Years -	University Hospital Heidelberg
A Study of SGN-35 (Brentuximab Vedotin) of Patients With Relapsed or Refractory PMLBCL	NCT02423291	Primary Mediast...	Brentuximab Ved...	18 Years -	Fondazione Italiana Linfomi - ETS
Lymphoma Patients Undergoing Mediastinal Radiotherapy in the Era of Modern Chemoradiation	NCT03969693	Mediastinal Lym... Hodgkin Lymphom... Non Hodgkin Lym...	Standard treatm...	15 Years - 80 Years	Chang Gung Memorial Hospital
Lymphoma Patients Undergoing Mediastinal Radiotherapy in the Era of Modern Chemoradiation	NCT03969693	Mediastinal Lym... Hodgkin Lymphom... Non Hodgkin Lym...	Standard treatm...	15 Years - 80 Years	Chang Gung Memorial Hospital
Pembrolizumab and Ibrutinib in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma	NCT02950220	B-Cell Lymphoma... Grade 1 Follicu... Grade 2 Follicu... Grade 3a Follic... Mediastinal Lym... Recurrent B-Cel... Recurrent Burki... Recurrent Diffu... Recurrent Folli... Recurrent Lymph... Recurrent Mantl... Recurrent Margi... Recurrent Walde... Refractory B-Ce... Refractory Burk... Refractory Diff... Refractory Foll... Refractory Lymp... Refractory Mant...	Ibrutinib Laboratory Biom... Pembrolizumab	18 Years -	Ohio State University Comprehensive Cancer Center

Spots Global Cancer Trial Database for mediastinal lymphoma