Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Infections

Rare Diseases

Lymphoma

Sarcoma, Kaposi

Castleman Disease

Lymphoma, Primary Effusion

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphoma, B-Cell

Lymphosarcoma

Kaposi Sarcoma

Unicentric Castleman Disease

Multicentric Castleman Disease

Primary Effusion Lymphoma

B-cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Pomalidomide

Etoposide phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Treatment na(SqrRoot) ve large cell lymphoma arising in KSHV-MCD

Part A: 5 mg po daily for 21 days (full course) Part A: 5 mg po daily for 4 days (short course) Part B: 5 mg po daily for 5 days (Phase I/II dose) Part C: Phase I/II dose) po daily Day 1-21 of 28 day cycle for up to 12 cycles.

Part A: 375 mg/m2 day 22 (full course) Part A: 375 mg/m2 day 5 (short course) Part A: 375 mg/m2 day 1 (omit pomalidomode) Part B: 375 mg/m2 day 1

Part B: 60 mg/m2/day po x 5 days (day 1-5

Part B: 50 mg/m2/day CIVI over 24 hrs x 4 days

Part B: 10 mg/m2/day CIVI over 24 hrs x 4 days

Part B: 0.4 mg/m2/day CIVI over 24 hrs x 4 days

Thomas S Uldrick, M.D.

Background:

- The chemotherapy combination DA-EPOCH-RP includes the drugs etoposide (E), prednisone (P), vincristine (O), cyclophosphamide (C), doxorubicin (H), rituximab (R), and pomalidomide (P). Researchers want to see if including pomalidomide will help people with two rare lymphomas.

Objectives:

- To study the safety and efficacy of the chemotherapy drugs DA-EPOCH-RP.

Eligibility:

- Adults at least 18 years old. They must have primary effusion lymphoma or large cell lymphoma arising from Kaposi sarcoma Herpesvirus-associated multicentric Castleman disease.

Design:

* Participants will be with screened with blood tests, scans, spinal tap, and bone marrow sample. They may have skin or lymph node samples taken and fluid removed from around some organs.
* Participants will have breathing and eye tests. A camera may take pictures inside their body.
* Participants will take pomalidomide alone by mouth for up to 21 days. Then they will get rituximab by intravenous (IV) catheter, which is a small tube that goes into a vein..
* Participants will have an IV inserted in an arm or chest vein to get the IV chemotherapy drugs, at the same time the will take pomalidomide by mouth for 5 days.
* They will get DA-EPOCH-RP in 21-day cycles. Most people will have 6 cycles.
* They will get 4 study drugs by IV for 5 days and 2 others by mouth for 5 days.
* They will get daily filgrastim injections in the skin until white blood counts are acceptable
* For 2 days of some cycles, methotrexate will be injected into the spinal fluid.
* After completing EPOCH-RP, some participants who have Kaposi sarcoma will be prescribed pomalidomide for 3-weeks, followed by a one week break, for up to 12 months.
* Participants will repeat the blood tests often. They will also have repeated medical history, physical exam, urine and stool tests, and pictures of any rashes associated with these lymphomas.
* Participants will have several follow-up visits over 4 years.

Background:

* Kaposi sarcoma herpesvirus (KSHV)-associated primary effusion lymphoma (PEL) and large cell lymphoma arising from KSHV-MCD are aggressive B cell neoplasms with clinicopathologic and molecular profiles distinct from other AIDS-related lymphomas.
* There are no prospective studies on these rare lymphomas. Clinical experience is limited; however, reported prognosis is poor, with median survival estimated at less than 6 months using conventional CHOP-like chemotherapy.
* Novel treatment is urgently needed for KSHV-associated lymphomas, and the therapeutic approach must take into account concurrent KSHV-associated malignancies which are commonly seen in this patient population
* Pomalidomide, an immune-modulatory derivative (IMiD) of thalidomide has in vitro

direct antitumor effect in KSHV-lymphomas as well as immune modulatory and antiangiogenic effects that may be beneficial in treating both KSHV-NHL and in many patients, concurrent KS.

* Rituximab, an anti-CD20 monoclonal antibody, has recently been shown to be an active agent in the management of KSHV-MCD. Although PEL is a CD20-negative tumor, advances in the understanding the biology of KSHV-infection of B-cells, the pathobiology of IL-6 syndromes in KSHV-MCD and KSHV-NHL, and clinical experience using rituximab in the treatment of KSHV-MCD support use of rituximab in the treatment of KSHV-NHL, especially in patients with concurrent KSHV-MCD.
* Modified dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA)-EPOCH is an anthracycline-based regimen that allows for personalization of dose-intensity showing that inclusion of etoposide and infusional administration decreases tumor cell resistance.
* The use of DA-EPOCH in combination with rituximab for the treatment of HIVassociated diffuse large B-cell lymphoma or Burkitt lymphoma has been shown to be safe and effective.
* Given the central role of controlling HIV viremia with combination antiretroviral therapy (cART) in the management of KSHV-associated malignancies, as well as the likely contribution of uncontrolled HIV viremia to PEL pathogenesis, cART will be employed as an important part of the treatment regimen.

Objectives:

Phase I:

-Determine the maximum tolerated dose and/or recommended phase II dose of pomalidomide in combination with DA-EPOCH-R.

Phase II

-Evaluate overall survival in treatment-naive patients with primary effusion lymphoma treated with pomalidomide in combination with, DA-EPOCH and rituximab (DAEPOCH- RP).

Eligibility:

-Adult patients greater than or equal to 18 years with pathology confirmed primary effusion lymphoma,

including extracavitary variant OR large cell lymphoma arising in the setting of KSHVassociated MCD.

* Lymphoma that is measurable or assessable
* Previously treated patients will be allowed if they have not been treated with modified DA-EPOCH or pomalidomide for KSHV-associated lymphoma
* Any HIV status
* Hematologic and biochemical parameters within pre-specified limits at baseline
* Willing to use effective birth control, as defined in the full protocol
* Neither pregnant nor breast feeding
* Excluded if other serious co-morbid condition that would prohibit administration of planned chemotherapeutic intervention is present

Design:

* This is a phase I/ II study of pomalidomide in combination with modified DA-EPOCH-R in patients with PEL and diffuse large cell lymphoma arising in the setting of KSHVMCD.
* Phase I of the study will evaluate escalating doses of pomalidomide (3 mg, 4 mg, and 5 mg) in combination with modified DA-EPOCH-R to determine safe and tolerable phase II pomalidomide dose for combination.
* Treatment in both Phase I and Phase II will have three parts. Patients will receive up to 21 days of pomalidomide monotherapy (part A), followed by 6 cycles of pomalidomide in combination with modified DA-EPOCH-R (part B), and then an optional up to 12 months of pomalidomide (part C) for patients with concurrent KS, symptomatic KSHVMCD, or KSHV inflammatory cytokine syndrome (KICS).
* Patients with HIV will generally be prescribed cART.
* In phase I, with 3 dose levels, 9-18 patients will be accrued (3-6 patients per level).
* In the phase II portion of the study, 15 evaluable patients will be enrolled over 48-60 months and 12 months follow-up after the last patient has enrolled, a 1-tailed 0.10 alpha level test would have 80% power to determine if OS curve would demonstrate a 1-year OS consistent with 45% or better and ruling out 20% or worse.

Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas

Phase I/II Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas (Primary Effusion Lymphoma and Large Cell Lymphoma Arising in KSHV-Associated Multicentric Castleman Disease)

National Cancer Institute (NCI)

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Nivolumab

Ipilimumab

Previous untreated patient with metastatic melanoma eligible for a Nivolumab treatment.

30 patients will be included in the arm.

Previous untreated patient with metastatic melanoma eligible for a Nivolumab + Ipilimumab treatment.

30 patients will be included in the arm.

Blood samples (52mL) will be taken at week 1, week 3, week 7, week 13, week 53 or at the progression.

Skin biopsies will be taken at week 1, week 7, week 53 or at the progression.

Blood and biopsy sampling

This is an open bi-centric prospective non-randomized study in patients with metastatic melanoma treated with a first line treatment of Nivolumab +/- Ipilimumab. The aim of the study is to characterize the immune cells modulations under anti-PD-1 +/- anti-CTLA4 and identify the differences between responder and non-responder patients.

Nivolumab +/- Ipilimumab Immunomonitoring in Metastatic Melanoma

Immune Modulation Study in Patients With Metastatic Melanoma Treated With a First Line Therapy of Nivolumab +/- Ipilimumab (IMMUNONIVO/MelpredictPD1).

Biological characteristics description of monocytes, dendritic cell and T cells subpopulations including different circulating suppressive subpopulations by immunomonitoring

Progression free survival (PFS) will be calculated as the period of time from the immunotherapy first administration to the first RECIST 1.1 disease progression

Overall survival (OS) will be calculated as the period of time from the immunotherapy first administration to the patient's death.

Immune adverse event description by clinical examination and correlation with biological characteristics of immune cells

Subtype of melanoma defined by histological analysis correlated with biological characteristics of immune cells

Immunity gene polymorphism defined by RNA sequencing correlated with biological characteristics of immune cells immune cells

Hospices Civils de Lyon

Symptoms and General Pathology

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Amino Acids

Fludarabine

Fludarabine phosphate

Tyrosine Kinase Inhibitors

Ibrutinib

Protein Kinase Inhibitors

Tyrosine

* Ibrutinib 420 mg PO daily for the duration of the study
* Fludarabine 25 mg/m2/day IV on days 1-5 of cycles 3 and 4

Ibrutinib 420mg PO daily for the duration of the study.

Fludarabine 25 mg/m2/day IV on days 1-5 of cycles 3 and 4

Andy Itsara, M.D.

This is a pilot phase 2 study investigating the safety and efficacy of ibrutinib combined with short-course fludarabine in previously untreated CLL patients. Ibrutinib will be given daily until disease progression or intolerable side effects occur. Fludarabine will be given in cycles 3 and 4. The primary efficacy endpoint is the rate of complete response after 6 cycles or 24 weeks. The primary safety endpoint is the rate of treatment discontinuation after 6 cycles or 24 weeks.

Chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL) are tumors of B cells that often affect elderly patients. 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 reduced with 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 patients with 17p deletion and for those who had at least one prior therapy. However, single-agent ibrutinib has limitations; the drug does not eliminate all the tumor cells, and, with time, the tumor cells may become resistant. Therefore, a combination of ibrutinib with other drugs could be beneficial. Here we chose fludarabine because it is a well-tolerated drug that has been used widely to treat CLL. Also, fludarabine can kill both malignant B cells and T cells that support the growth of leukemia cells. With this approach, we hope to restore a healthier immune system.

This study will investigate the safety and efficacy of ibrutinib combined with fludarabine. This protocol is intended for previously untreated CLL patients. Ibrutinib will be given daily until disease progression or intolerable side effects occur. Fludarabine will be given only in cycles 3 and 4.

A Phase II Study Using Ibrutinib and Short-Course Fludarabine in Treatment-Naive CLL

A Pilot Phase II Study Using Ibrutinib and Short-Course Fludarabine in Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Rate of complete response at 24 weeks or after 6 cycles. Response assessment was conducted according to the guidelines from the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL).

Rate of treatment discontinuation within the first 24 weeks or 6 cycles due to intolerable side effects from study therapy

National Heart, Lung, and Blood Institute (NHLBI)

The AE reporting period for this study begins when the participant takes the first dose of study drug and continues until the last follow-up on the study. Participants will continue on study until disease progression or intolerable side effects occur.

Open-label study of ibrutinib and a short-course fludarabine in previously untreated participants with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Ibrutinib is administered orally, 420 mg daily for days 1-28 from Cycle 1 up to Cycle 27. Fludarabine dose is 25 mg/m2/day on days 1-5 of cycles 3 and 4.

Ibrutinib With Fludarabine in Patients With CLL or SLL

Open-label study of ibrutinib and a short-course fludarabine in previously untreated participants with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Ibrutinib is administered orally, 420 mg daily for duration of study. Fludarabine dose is 25 mg/m2/day on days 1-5 of cycles 3 and 4.

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Inhye Ahn, M.D.

Rate of Complete Response at 24 Weeks

Rate of Treatment Discontinuation Within the First 24 Weeks

Overall Study

Pharmaceutical Solutions

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immune Checkpoint Inhibitors

Nivolumab (dose equal to 3mg/kg), 10 mg/ml solution for infusion. injection of Nivolumab every two weeks from day 0 and until relapse, toxicity motivating withdrawal or temporary suspension of treatment or up to 54 weeks.

Blood sampling at different time

Blood samples (44mL) will be taken before starting treatment with Nivolumab and at week 2, week 12, week 54 or at relapse (before week 54)

blood sampling

injection of Nivolumab every two weeks from day 0 and until relapse, toxicity motivating withdrawal or temporary suspension of treatment or up to 54 weeks.

This is an open mono-centric prospective non-randomized study in patients with metastatic melanoma treated with Anti-PD1 monoclonal antibodies (Nivolumab). The aim of the study is to identify the immune cells modulations differences between patients who present a complete, partial or stable response and patients who have non-response to the therapy in order to establish an improving response rate strategy.

Immune Modulation Study in Patients With Metastatic Melanoma Treated With Anti-PD1 Monoclonal Antibodies

absolute number / mm 3 of dendritic cells

% of cells producing cytokines in dendritic cells

absolute number / mm 3 of different subpopulations of T lymphocyte

% of cells producing cytokines in subpopulations of T lymphocytes

% of cells producing cytokines in monocytes

absolute number / mm 3 of different population of cells and % of cells producing cytokines in the different population of cells will be correlated with the progression free survival

absolute number / mm 3 of different population of cells and % of cells producing cytokines in the different population of cells will be correlated with the overall survival

predictive factors like histological and cytological initial tumor type, initial immunological status will be evaluated at inclusion and correlated with the response

absolute number / mm 3 of different population of cells and % of cells producing cytokines in the different population of cells will be correlated with treatments received prior to inclusion

absolute number / mm 3 of different population of cells and % of cells producing cytokines in the different population of cells will be correlated with autoimmune side effects, based on CTCAE classification

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas	NCT02228512	Large Cell Lymp... Primary Effusio...	Pomalidomide Rituximab Prednisone Etoposide Doxorubicin Vincristine Cyclophosphamid...	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Nivolumab +/- Ipilimumab Immunomonitoring in Metastatic Melanoma	NCT03225365	Metastatic Mela...	Blood and biops...	18 Years -	Hospices Civils de Lyon
A Phase II Study Using Ibrutinib and Short-Course Fludarabine in Treatment-Naive CLL	NCT02514083	Chronic Lymphoc... Small Lymphocyt...	Ibrutinib Fludarabine	18 Years -	National Institutes of Health Clinical Center (CC)
Immune Modulation Study in Patients With Metastatic Melanoma Treated With Anti-PD1 Monoclonal Antibodies	NCT02626065	Metastatic Mela...	blood sampling Nivolumab	18 Years -	Hospices Civils de Lyon

Spots Global Cancer Trial Database for immune modulation