Infections

All Conditions

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Communicable Diseases

Epstein-Barr Virus Infections

Lymphoproliferative Disorders

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Lymphatic Diseases

Immunoproliferative Disorders

Post-transplant Lymphoproliferative Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Bortezomib

Antineoplastic Agents, Immunological

Immunologic Factors

This is a single arm trial adding the new drug bortezomib to the standard drug rituximab

Given intravenously on days 1, 4, 8 and 11 of every cycle

bortezomib

given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles

rituximab

Jeremy Abramson, MD

Post transplant lymphoproliferative disease (PTLD) is a type of B-cell non-Hodgkin lymphoma that occurs in patients with weakened immune systems due to immunosuppressive medications taken after organ or stem cell transplantation. This is usually related to a virus called Epstein-Barr (EPV). Rituximab is a type of drug called an "antibody" that specifically destroys both normal and cancerous B-cells, and is commonly used for PTLD. Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) to treat multiple myeloma and a B-cell non-Hodgkin lymphoma called Mantle Cell Lymphoma, and shows significant activity in lymphoma cells caused by EBV. In this research study, we hope to learn if the addition of bortezomib to rituximab treatment can increase the rate of complete remissions and cures of PTLD after organ or stem cell transplant.

* Both rituximab and bortezomib will be given to participants intravenously. Each cycle of treatment will consist of 21 days. Rituximab will be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles. Bortezomib will be given on Days 1, 4, 8 and 11 of every cycle. Participants will receive a maximum of 4 cycles.
* The following study procedures will be performed during each cycle throughout the study: Medical history review; Physical exam; Performance Status; Questionnaire; Blood draws and; PET/CT scans (After cycles 2, 4 and 6 only).
* After Cycle 4, if the study doctor feels the participant has had a complete response to treatment, then they will continue onto the Post-Treatment Surveillance period, which will consist of regular clinic visits over two years.
* However, if the study doctor feels the participant has had a partial response to treatment and that they may benefit from continuing, they will receive an additional two cycles of bortezomib and be given daily tablets of the antiviral drug valganciclovir to help further target EBV.

Bortezomib Plus Rituximab for EBV+ PTLD

Bortezomib Plus Rituximab for EBV + Post Transplant Lymphoproliferative Disease (PTLD)

Overall response rate includes both complete and partial responses assessed by PET/CT following completion of therapy. Response was evaluated using the International Working Group criteria for lymphoma response. The complete list of criteria used to evaluate response is too long to be detailed in the allotted space here, but response is defined more generally as:

* Complete Response (CR): Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
* Partial Response (PR): ≥ 50% decrease in the sum of the products of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses.

The number of participants with complete responses as assessed by PET/CT following completion of therapy. Response was evaluated using the International Working Group criteria for lymphoma response.

Complete Response (CR): Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.

Percent of participants with progression free survival (alive without disease progression) six months after registration. Progression was evaluated using the International Working Group criteria for lymphoma response.

\> Progressive Disease (PD) or Relapsed Disease (RD):

1. Appearance of any new lesion \> 1.5 cm in any axis during or at end of therapy. Increased Radiolabeled\[18F\]-2-fluoro-2-deoxy-D-glucose (FDG) uptake in a previously unaffected site will be considered PD/RD only after confirmation by other modalities.
2. ≥ 50% increase from nadir in the sum of the products of the largest diameters (SPD) of any previously involved node, or in a single involved node, or in the sizes of other lesions.
3. ≥ 50% increase in the longest diameter of any single previously identified node \> 1 cm in its short axis.
4. PET (positron emission tomography) positive prior to therapy: post-treatment PET should be positive unless lesion is too small to be detected with current PET sys

The percent of participants surviving at 6 months and 1 year.

The Mean epstein barr virus (EBV) viral load at the given time points.

The toxicities experienced by participants that were deemed to be related to the study treatment. Data is shown as the number of participants that experienced any grade toxicity that was deemed to be related to treatment. Toxicities were assessed with the use of Common Toxicology Criteria for Adverse Events (CTCAE).

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Beth Israel Deaconess Medical Center

Millennium Pharmaceuticals, Inc.

Massachusetts General Hospital

Director, Lymphoma Program

Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.

This is a single arm trial adding the new drug bortezomib to the standard drug rituximab

bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle

rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles

Rituximab Plus Bortezomib

Age, Continuous

≤ 50 years

51-60 years

61-70 years

71+ years

Age, Customized

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Eastern Cooperative Oncology Group (ECOG) Performance Status 0: Asymptomatic (Fully active)

1. Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out light work)
2. Symptomatic \<50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities)
3. Symptomatic, \>50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours)
4. Bedbound (Completely disabled. Cannot carry on any self-care)
5. Death

ECOG Performance Status

PTLD/polymorphic

PTLD/monomorphic, DLBCL

World Health Organization (WHO) disease classification.

* PTLD: Post-transplant lymphoproliferative disease
* DLBCL: diffuse large B-cell lymphoma.

WHO Classification

Jeremy Abramson, M.D

Overall Response Rate

Complete Response Rate

Six-Month Progression Free Survival

6 month

12 Month

Overall Survival

Baseline

End of Cycle 1 (21 days)

End of Cycle 2 (42 days)

End of Cycle 3 (63 days)

End of Cycle 4 (84 days)

Not all participants completed four cycles of treatment. The number of participants analyzed in each row differs according to the number of participants available for analysis at each time point.

Effects of Bortezomib/Rituximab on EBV Quantitative Viral Load

Febrile Neutropenia

Leukocytosis

Lymph Node Pain

Abdominal Pain

Nausea

Neutrophil Count Decreased

Platelet Count Decreased

Alkalosis

Anorexia

Peripheral Sensory Neuropathy

Treatment Related Toxicities

Overall Study

Disease Attributes

Burkhard Toenshoff, MD, PhD

Question:

In which stage of an EBV-infection is a selective reduction of immunosuppressive medication reasonable to minimize the risk for PTLD, without putting the transplant recipient at risk of acute rejection episodes due to under immunosuppression?

Aim of study:

Identification of patients at high-risk for PTLD.

PTLD represents a heterogeneous group of abnormal lymphoid proliferations, generally of B-cells, that occur in the setting of ineffective T-cell function because of pharmacological immunosuppression. Because the vast majority of PTLDs are associated with Epstein-Barr virus (EBV) infection, surveillance of EBV infection may have the potential to prevent the development of PTLD by early intervention. However, the cut-off values of "high" EBV viral load remain badly defined due to a lack of prospective studies and assay standardization. The aim of this ongoing multicenter prospective study is the serial detection of primary EBV infection or reactivation in a homogeneous patient population of pediatric renal transplant recipients during the first 2 years posttransplant by the combined analysis of quantitative EBV viral load by a standardized quantitative PCR technique, EBV serology and EBV-specific T-lymphocytes for the identification of high-risk patients.

EDTA plasma for EB viral load, serum for differentiated serology and sodium heparine whole-blood for EBV-specific t cells

EBV Infection as a Risk Factor for PTLD in Pediatric and Adult Renal Transplant Recipients

Surveillance of EBV Infection as a Risk Factor for PTLD in Pediatric and Adult Renal Transplant Recipients - a Multicenter Prospective Study

Klinik für Kinder- und Jugendmedizin

EBV in pediatric RTx patients

Neoplasms

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Lymphosarcoma

Hodgkin Lymphoma

B-cell Lymphoma

Immunomodulating Agents

Treatment consist of up to 5 doses of 2x10E7 cells/m2 administered intravenously every 2 weeks.

baltaleucel-T

Kurt Gunter, MD

To investigate the efficacy of autologous Epstein-barr virus (EBV)-specific T cells for the treatment of EBV positive Diffuse Large B Cell Lymphoma (DLBCL), Hodgkin Lymphoma (HL) and Post-transplant Lymphoproliferative Disease (PTLD) after failing first line treatment.

Cellular Immunotherapy for Viral Induced Cancer - EBV Positive Lymphomas

A Phase 2 Open Label Study to Investigate the Safety and Clinical Activity of Autologous EBV-specific T Cells (CMD-003) for the Treatment of Patients With EBV Positive Lymphomas

Best single observed response, complete response (CR) or partial response (PR) per Lugano 2014 Disease Response Criteria, during 12 month follow-up.

Adverse events will be recorded from the time of the first investigational cell product dose is administered until 30 days after the last administration. Serious events recorded for up to 1 year after administration.

Cell Medica Ltd

Prescheduled hospital admissions, hospital admissions for elective surgery, transfusions, diagnostic procedures are not considered to be SAEs. Events related to progression of the underlying malignancy will likewise not be categorized as serious.

Treatment consist of up to 5 doses of 2x10E7 cells/m2 administered intravenously every 2 weeks.

baltaleucel-T: Autologous EBV-specific T cells

Baltaleucel-T

Age, Categorical

Ethnicity (NIH/OMB)

Relapse or refractory HL disease post brentuximab vedotin (BV) or unable to tolerate BV.

Cohort B - Hodgkin Lymphoma (HL)

Early termination leading to small numbers of subjects analyzed.

Dr. Kurt Gunter (Chief Medical Officer)

Treatment consist of up to 5 doses of 2x10E7 cells/m2 administered intravenously every 2 weeks.

balteleucel-T: Autologous EBV-specific T cells

Balteleucel-T

Subject was withdrawn early before first disease assessment timepoint.

Best Overall Response

Adverse Events

Diseases and Abnormalities at or Before Birth

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Skin and Connective Tissue Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Congenital Abnormalities

Influenza, Human

Hematologic Neoplasms

Neoplasm, Residual

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Chromosome Aberrations

Monosomy

Chromosome Disorders

Hematologic Diseases

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Neoplastic Processes

Bone Marrow Diseases

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Aneuploidy

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Neurofibromatosis

Neurofibromatosis Type 1

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Anticonvulsants

Nootropic Agents

Fludarabine

Fludarabine phosphate

Melphalan

Levetiracetam

Busulfan

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.

Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.

Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.

Busulfan 82.1 mg\*hr/L IV on days -5 to -2 or days -8 to -5

200 mg/m2 intravenous given once on day-1

As seizures have occurred following high dose busulfan, all patients will be treated with Keppra beginning day -6 and continuing until day -1 per institutional guidelines.

Margaret MacMillan

This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bortezomib Plus Rituximab for EBV+ PTLD	NCT01058239	Post-transplant... Solid Organ Tra... Stem Cell Trans... Epstein Barr Vi...	bortezomib rituximab	18 Years -	Massachusetts General Hospital
EBV Infection as a Risk Factor for PTLD in Pediatric and Adult Renal Transplant Recipients	NCT00963248	Epstein-Barr Vi...		-	Klinik für Kinder- und Jugendmedizin
Cellular Immunotherapy for Viral Induced Cancer - EBV Positive Lymphomas	NCT02763254	Hodgkin Lymphom... Lymphoma, Large... Post-transplant...	baltaleucel-T	12 Years -	Cell Medica Ltd
MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies	NCT05735717	Hematologic Mal... Acute Leukemia Remission Acute Myeloid L... Acute Lymphobla... AML TP53 Intrachromosoma... Cytogenetic Abn... CNS Leukemia Minimal Residua... Myelodysplasia Juvenile Myelom... Somatic Mutatio... PTPN11 Gene Mut... N-RAS Gene Ampl... Neurofibromatos... NF1 Mutation CBL Gene Mutati... Monosomy 7 Chromosome Abno... Fetal Hemoglobi...	Fludarabine Busulfan Melphalan Rituximab Levetiracetam	- 60 Years	Masonic Cancer Center, University of Minnesota
EBV Infection as a Risk Factor for PTLD in Pediatric and Adult Renal Transplant Recipients	NCT00963248	Epstein-Barr Vi...		-	Klinik für Kinder- und Jugendmedizin

Spots Global Cancer Trial Database for ptld

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

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