Neoplasms

Blood and Lymph Conditions

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Immune System Diseases

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Rare Diseases

Leukemia

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Chronic Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Disease Attributes

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Chromosome 17p Deletion

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Pembrolizumab

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

Ibrutinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Ibrutinib, Fludarabine, and Pembrolizumab combination therapy will be administered in participants with High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). Ibrutinib will be administered daily by mouth starting cycle -3 at 420 mg until end study or disease progression or intolerable side effects occur. Fludarabine will be administered intravenously only on cycle -2 at 25mg/m\^2 x5 days. Pembrolizumab will be administered intravenously every 3 weeks at 200 mg starting from cycle 1 through cycle 17 or 1 year of immunotherapy phase.

Ibrutinib will be administered daily by mouth starting cycle -3 at 420 mg until end study or disease progression or intolerable side effects occur.

Fludarabine will be administered intravenously only on cycle -2 at 25mg/m\^2 x5 days.

Pembrolizumab will be administered intravenously every 3 weeks at 200 mg starting from cycle 1 through cycle 17 or 1 year of immunotherapy phase.

Adrian U Wiestner, M.D.

Background:

Chronic lymphocytic leukemia and small lymphocytic lymphoma (hereby referred as CLL) are tumors of B cells. A subset of patients categorized as high-risk CLL has a poor clinical outcome when treated with conventional chemotherapy. This single-arm, phase II study investigates the combination of ibrutinib, fludarabine and pembrolizumab for treatment of CLL. Ibrutinib is an orally administered therapy for CLL. Fludarabine is a well-tolerated drug that has been widely used to treat CLL. Also, fludarabine can modulate CLL cells as well as immune cells that support the growth of CLL cells. Pembrolizumab recruits immune cells to attack CLL cells. With this approach we hope to achieve a greater reduction in CLL cells than with single agent ibrutinib and to restore healthier immune system that could contribute to durable responses.

Objective:

To investigate the rate of complete response to ibrutinib, short course fludarabine and pembrolizumab.

Eligibility:

Patients with active CLL meeting treatment indications defined by 2008 International Workshop on CLL (IWCLL) consensus guideline.

High-risk CLL defined by one of the following:

* Relapsed/refractory disease status, or
* Presence of high-risk mutations regardless of prior treatment status: deletion 17p, TP53 mutation, NOTCH1 mutation, SF3B1 mutation, MYC aberration, or complex cytogenetics.

Design:

This is a single-arm, open-label phase II study.

Timeline: Treatment on this study is given in cycles from cycle -3 to 17, then in months beyond cycle 17. Cycles -3 to -1 are 28-day cycles. Cycles 1 to 17 are 21-day cycles. After completion of 1 year of pembrolizumab, the time on study is by chronological months on study from starting pembrolizumab.

Treatment plan:

* Ibrutinib is given starting from cycle -3 and continuously until disease progression or intolerable side effects occur.
* Fludarabine is given on D1-D5 on cycle -2 only
* Pembrolizumab is given every 3 weeks starting from cycle 1 for 1 year.
* Minimal residual disease will be measured at 2 years from cycle 1 to determine the need for long- term treatment with ibrutinib.

  * Previously-untreated patients who achieve minimal residual disease negativity will stop ibrutinib.
  * Patients who do not achieve minimal residual disease negativity or who has Relapsed/refractory CLL will continue ibrutinib.

Background:

This study investigates the combination of ibrutinib, fludarabine and pembrolizumab for treatment of CLL. Chronic lymphocytic leukemia and small lymphocytic lymphoma (hereby referred as CLL) are tumors of B cells. A subset of patients categorized as high-risk CLL has a poor clinical outcome when treated with conventional chemotherapy. High-risk CLL is defined by relapsed/refractory disease status, or the presence of high-risk mutations, such as deletion 17p, TP53, and NOTCH1. While the cause of CLL is still unclear, studies have indicated critical factors required for the tumor cells. First, CLL cells grow and survive because they receive signals through the B-cell receptor (BCR); and second, CLL cells benefit from interactions with other cells, especially T cells.

The stimulation through the BCR can be blocked by ibrutinib, which is an oral drug that selectively inhibits Bruton's tyrosine kinase (BTK). In clinical trials, ibrutinib demonstrated safety and high response rates in patients with high-risk disease. Ibrutinib has gained FDA approval as a treatment for CLL regardless of prior treatment or cytogenetic status. However, single-agent ibrutinib has limitations; the drug does not eliminate all tumor cells and, with time, the tumor cells may become resistant. Therefore, combination of ibrutinib with other drugs could be beneficial.

Objectives:

-To investigate the rate of complete response to ibrutinib, short course fludarabine and pembrolizumab.

Key eligibility criteria:

Patients with active CLL meeting treatment indications defined by 2008 International Workshop on CLL (IWCLL) consensus guideline.

High-risk CLL defined by one of the following:

Relapsed/refractory disease status, or

Presence of high-risk mutations regardless of prior treatment status: deletion 17p, TP53 mutation, NOTCH1 mutation, SF3B1 mutation, MYC aberration, or complex cytogenetics.

Ibrutinib, Fludarabine, and Pembrolizumab in High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

A Phase II Study Of Ibrutinib, Fludarabine, and Pembrolizumab in High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Rate of complete response with combination ibrutinib, fludarabine, and pembrolizumab in patients with high-risk and/or relapsed/refractory chronic lymphocytic leukemia and small lymphocytic leukemia. Response assessments defined by IWCLL 2008 guidelines incorporating the 2012 and 2013 clarifications for patients treated with kinase inhibitors. Complete response defined as: Lymphadenopathy is none \> 1.5 cm; No Splenomegaly or Hepatomegaly; Blood Lymphocytes \<4000/uL; Bone Marrow is normocellular, \<30% lymphocytes, no B-lymphoid nodules; Platelet count \>100,000/uL; Hemoglobin \> 11.0 g/dL and Neutrophils \>1500/uL. Partial response is defined by meeting 2 criteria: Lymphadenopathy decrease \> or = 50%; Splenomegaly or Hepatomegaly decrease \> or = 50%; Blood Lymphocytes decrease \> or = 50% from baseline; Platelet is \> 100,000/uL or increase \> or = 50% over baseline; Hemoglobin is \> 11.0 g/dL or increase \> or = 50% over baseline; Neutrophils is \> 1500/uL or increase \> or = 50% over baseline.

Tolerability of the combination regimen, Overall response rate (ORR), Duration of response (DOR), Best response, Minimal residual disease (MRD) status, Progression-free survival (PFS), Overall survival (OS), To explore the biologic effects on B- and T-cell subsets and function, To identify predictors of clinical response.

National Heart, Lung, and Blood Institute (NHLBI)

Ibrutinib, Fludarabine, and Pembrolizumab in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Adrian Wiestner, M.D., Ph.D., Principal Investigator

Includes all participants that completed the 1 year evaluation

Number of Participants With Complete Response of the Combination of Ibrutinib, Fludarabine, and Pembrolizumab in Patients With High-risk and/or Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia

Tolerability, Response and Best Response, Survival

Conditioning Phase (12 Weeks)

Immunotherapy Phase (1 Year)

Follow-up Phase (Extension Study)

Patients with Chronic Lymphatic Leukemia treated with splenic irradiation

splenic irradiation

Jacques Borger, dr.

Retrospective evaluation on the effect of splenic irradiation on clinical and hematological response and toxicity in patients with chronic lymphatic leukaemia (CLL).

The study will include patients with CLL treated with splenic irradiation in Maastro Clinic, Maastricht, The Netherlands, Maxima Medisch Centrum Veldhoven/Catharina hospital, Eindhoven, The Netherlands and Modena hospital, Modena, Italy. Data will be collected from patient records in an uniform database. Data will include demographic data, CLL stadium (RAI and Binet) at diagnosis and at the time of irradiation treatment, clinical data at diagnosis (haematology), splenic irradiation data, follow-up data such as date of progression or death

Evaluation of Splenic Irradiation in Chronic Lymphatic Leukemia

Evaluation of Splenic Irradiation in Chronic Lymphatic Leukemia (CLL)

Clinical and haematological response measured by number of leucocytes and thrombocytes during and after irradiation. Hemoglobin and size of spleen during and after irradiation in the time period 2000 tot 2013

Progression of chronic Lymphatic leukaemia after irradiation in the time period 2000 tot 2013

Patients will be followed from the time of splenic irradiation to death in the time period of 2000 tot 2013

Toxicity of splenic irradiation during and after irradiation measured by evaluating clinical toxicity based on the CTCAE version 3.0 during and after irradiation (2000 to 2013)

Maastricht Radiation Oncology

Heart and Blood Diseases

Atrial Fibrillation

Hypertension

Lymphoma, Mantle-Cell

Lymphoma, Non-Hodgkin

Mantle Cell Lymphoma

Mariana Mirabel, MD, PHD

Mariana Mirabel, MD, PhD

Ibrutinib (a tyrosine kinase inhibitor targeting Bruton) is a standard of treatment in haematology. According to retrospective data, atrial fibrillation and systemic hypertension are common ibrutinib-related advserse events. The investigators aim at prospectively establishing the incidence of thesedrug related advsere events through clinical monitoring and attempt at identifying populations at risk.

Atrial Fibrillation in Patients Receiving Ibrutinib

Etude de l'Incidence et Des Facteurs prédictifs de la Survenue de Fibrillation Atriale Sous Ibrutinib

Evaluate the incidence of cardiotoxicity (composite endpoint) in a cohort of patients referred to a cardio-oncology before initiation of ibrutinib.

Number of patients with supra-ventricular arrythmias

Number of patients with systemic hypertension

Compare advsere events in patients with supr-ventricular arrhythmias according to the continuation or discontinuation of ibrutinib

Correlation between anti thrombotic strategies and cardiovascular outcomes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ibrutinib, Fludarabine, and Pembrolizumab in High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	NCT03204188	B-Cell Chronic ... B-Lymphocytic L... Chronic Lymphoc... Leukemia, Chron... Leukemia, Chron... Leukemia, Lymph... Leukemia, Lymph... Lymphocytic Leu... Lymphocytic Leu...	Ibrutinib Fludarabine Pembrolizumab	18 Years -	National Institutes of Health Clinical Center (CC)
Evaluation of Splenic Irradiation in Chronic Lymphatic Leukemia	NCT02020109	Leukemia, Chron...	splenic irradia...	18 Years -	Maastricht Radiation Oncology
Atrial Fibrillation in Patients Receiving Ibrutinib	NCT04407845	Leukemia, Chron... Mantle Cell Lym...		18 Years -	European Georges Pompidou Hospital

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