Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoproliferative Disorders

Hodgkin Disease

Waldenstrom Macroglobulinemia

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

People that have blood or lymph node cancer, or a family history of leukemia or lymphoma.

Douglas R Stewart, M.D.

Background:

* Individuals may be prone to develop blood or lymph node cancers (leukemia or lymphoma) for a variety of reasons, including genetic predisposition to these cancers, environmental exposures or other medical conditions.
* Studies of people and families at high risk of cancer often lead to clues about their cause that may also be important regarding the sporadic occurrence of these cancers in the general population.
* Identifying genetic or environmental factors that play a role in the development of these diseases may be important in developing prevention trials, screening programs and treatments.

Objectives:

* Describe the cancers and other conditions in families with blood or lymph node cancer.
* Find and describe genes that may cause blood and lymph node cancer, and understand how they work in families.
* Use laboratory methods to try to determine if it is possible to identify who is at highest risk of blood or lymph node cancer.
* Test how genes act with other factors to alter the risk of disease, its severity or its manifestations in families.

Eligibility:

* Individuals of any age with a personal or family history of a blood or lymph node cancer.
* Individuals with a personal or family history of medical conditions or environmental exposures that may predispose to blood or lymph node cancer.

Design:

* Participants complete questionnaires about their personal and family medical history and provide consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with blood or lymph node cancer, tumors, or other related illnesses for whom they are the legally authorized representative.
* Participants donate a sample of blood or cheek cells, or a lock of hair for genetic studies.
* Patients may also be evaluated at the NIH Clinical Center by one or more of the following specialists: cancer doctor or blood specialist, medical geneticist, research nurses or clinical social worker. They may have blood and urine tests and a cheek swab or mouth wash to collect cheek cells. Some patients may also be asked to have x-rays and routine imaging, such as CT scans or ultrasound tests, cell surface markers, skin biopsy, and, with special consents, bone marrow biopsy, MRI or PET scans, apheresis or fluorescein angiography and photography.

Background:

Persons may be prone to develop hematologic or lymphoproliferative cancer for a variety of reasons including: inherited predisposition of benign, premalignant, or malignant conditions; environmental exposures shared by family members; previous tumors or preneoplastic conditions; immune deficiency; or stochastic processes

Investigations of individuals and families at high risk of cancer often lead to etiologic clues that may be important in the sporadic counterparts of these cancers in the general population

Identification of etiologically important genetic factors could inform chemoprevention trials, screening programs, and treatment of hematologic and lymphoproliferative cancers

Objectives:

To evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing to hematologic cancer

To evaluate potential precursor states of malignancy in families at risk

To quantify the risks of specific tumors in family members and define syndromic constellations

To identify, map, characterize, clone, and determine function of tumor susceptibility genes

To validate and test associations of biomarkers with risk

To identify genetic determinants, environmental factors, and gene-environmental interactions conferring cancer risk in individuals and families

To identify differences and similarities between the familial and sporadic condition

To educate and counsel study participants about their risk of hematologic malignancy including prevention recommendations and early detection activities when known

To develop syndrome-specific educational materials for medical professionals and high-risk family members

Eligibility:

On referral, persons \>= 11 months will be included only because of personal history, and persons \>/=18 years can also be included because of personal or family history of the parameters listed below:

* a medical history of hematologic/lymphoproliferative malignancy of an unusual type, pattern, or number or
* there are known or suspected factor(s) predisposing to hematologic malignancy, either genetic or congenital factors, environmental exposure, or unusual demographic features

  * For familial neoplasms, two or more living affected cases among family members are generally required

Design:

This is a prospective study. Families are studied long-term using a cohort approach.

The study design and evaluation vary by the specific type of familial neoplasm being studied

The overall approach to eligible families includes defining affection status, characterization of disease, localization of genetic loci, identification of genes, evaluation of phenotype/genotype correlations, estimation of risk of the disease associated with carrier

status and identification of other risk factors that modify penetrance (genetic, environmental, and host factors)

Clinical, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Hematologic Cancer

Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Blood and Lymph Node Malignancy

To define the clinical spectrum and natural history of familial blood and lymph node malignancies and susceptibility states over time.

National Cancer Institute (NCI)

Sarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Participants complete an online survey over 5-10 minutes asking how they would manage lymph node basins in the extremity sarcoma.

Survey Administration

Christina L Roland

This study investigates the surgical management of lymph node basins for extremity and trunk soft tissue sarcoma (ETSTS) to identify and better understand the surgical practice patterns of sarcoma surgeons. ETSTS has been known to spread to distant locations including lymph nodes, with some subtypes of the disease spreading to lymph nodes more than others. This has led to sarcoma surgeons to treat patients differently from one another, including those with more lymph node involvement. The purpose of this study is to investigate the practice patterns of ETSTS surgeons.

PRIMARY OBJECTIVES:

I. Identify the practice patterns of sarcoma surgeons with respect to management of lymph node basins for extremity and trunk soft tissue sarcomas (ETSTS).

II. Identify when surgeons would perform sentinel lymph node biopsy and/or lymph node dissection for ETSTS and if management differs for high-risk subtypes of sarcoma that are more likely to have nodal metastases.

III. Identify differences in practice patterns between surgical oncologists and orthopedic oncologic surgeons.

OUTLINE:

Participants complete an online survey over 5-10 minutes asking how they would manage lymph node basins in the extremity sarcoma.

Identification of Surgical Management of Lymph Node Basins and Surgical Practice Patterns Among Sarcoma Surgeons

Survey of Extremity and Trunk Sarcoma Surgeons Regarding Surgical Management of Lymph Node Basins

Will identify the practice patterns of sarcoma surgeons with respect to management of lymph node basins for extremity and trunk soft tissue sarcomas (ETSTS).

Will identify when surgeons would perform sentinel lymph node biopsy and/or lymph node dissection for ETSTS, and if management differs for high-risk subtypes of sarcoma that are more likely to have nodal metastases.

Will identify differences in practice patterns between surgical oncologists and orthopedic oncologic surgeons.

M.D. Anderson Cancer Center

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

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Prime Phase -Nivolumab 240mg, IV Infusion, every two weeks starting with Cycle 2 ( Cycles 2, 4, 6) for 6 weeks in combination with CMP-001, 5mg, Injection, at Week 1 and the remaining injections, 10 mg will be administered Weeks 2 -7.

Boost Phase -Nivolumab 240mg, IV Infusion, every two weeks, over a 46 week period in combination with CMP-001, 5mg, administered every 4 weeks for 1 year.

A molecule comprised of a 30 nucleotide strand, flanked by 10 guanines on either end. The nucleotide strand is surrounded by a Qβ viral-like protein. The intended mechanism of action of CMP-001 in oncology is the activation of TLR9 in pDC within the tumor or the tumor-draining lymph nodes (tumor-associated pDC).

CMP-001

A fully human Ig G4 antibody that blocks PD-1. Nivolumab was initially approved by the FDA for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Nivolumab has also been FDA approved to treat patients with advanced (metastatic) squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy, as well as advanced renal cell carcinoma.

Diwakar Davar, MD

The purpose this research study is to determine if the combination of nivolumab and CMP-001 improves the likelihood of eradicating (destroying) disease in the lymph node (pathologic response rate).

Patients are being asked to take part in this clinical research study because they have stage IIIB, IIIC or IIID cutaneous (or unknown primary) melanoma with lymph node disease and have yet to undergo surgery. There are two phases, Prime Phase and a Boost Phase. If they participate they will receive nivolumab in combination with CMP-001 for a total of 7 weeks (Prime Phase) prior to surgery. Surgery will be performed approximately 2-4 weeks after completion of the Prime Phase. After recovery from surgery patients will receive additional nivolumab in combination with CMP-001 for approximately 46 additional weeks (Boost Phase).

The main goal of this research study to determine if the combination of nivolumab and CMP-001 improves the likelihood of eradicating (destroying) disease in the lymph node (pathologic response rate). Pathologic responses are associated with improved relapse-free and overall survival in melanoma.

Prior to surgery (Prime Phase) Nivolumab 240mg, will be administered as a 30-minute IV infusion on an outpatient basis. During the Prime Phase, 3 cycles of Nivolumab will be administered every 2 weeks over a 6 week period starting with cycle 2, cycle 4 and then cycle 6.

Prior to surgery (Prime Phase) CMP-001 will be given as an injection from a syringe weekly for a total of 7 weeks. The first injection (week 1), 5mg, will be applied directly into the skin and the remaining injections, 10mg will be administered, will be given intra-tumorally for weeks 2-7.

Surgery will be performed to the cancerous lymph node 2-4 weeks after the Prime Phase is completed.

After recovery from surgery (Boost Phase) Nivolumab will be administered at 240mg every 2 weeks or 480 mg every 4 weeks depending on the physician's preference. CMP-001, 5mg, will be administered by injections intra-tumorally every 4 weeks for up to 54 weeks.

Patients will be followed to assess for survival status until death, withdrawal of consent, or the end of the study, whichever occurs first. This will be done every 3 months.

CMP-001 in Combo With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease

Neoadjuvant Phase II Study of TLR9 Agonist CMP-001 in Combination With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease

Circulating and intra-tumoral immune cells, including T-cells (CD8, CD4, Tregs) and antigen-presenting cells (monocytes, macrophages, MDSCs), will be compared pre and post nivolumab and CMP-001 combination treatment.

TCR clonality/diversity will be compared pre and post nivolumab and CMP-001 combination treatment.

Genetic and transcriptomic signatures will be compared between patients who do and do not respond to study treatment.

Tumor imaging characteristics will be compared between patients who do and do not respond to study treatment.

Distribution of pathologic response in the 30 evaluable patients. Major pathologic response was defined on surgical specimens analyzed by blinded two independent dermatopathologists using immune related pathologic response criteria (irPRC). Residual viable tumor (RVT) (wherein RVT = viable tumor area/total tumor bed area) was calculated depending on the quantity of viable malignant cells on H\&E-stained slides and confirmatory SOX-10-stained representative sections in ambiguous cases; and thresholds defined as follows: complete response (pCR, 0% RVT), major response (pMR, 0%\< RVT ≤10%), partial response (pPR, 10%\< RVT ≤50%), and pNR (RVT \>50%).

Complete response \[CR\], partial response \[PR\], stable disease, per RECIST v1.1 criteria. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Length of time from the initiation of treatment that patients survive without recurrence of disease. Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression.

Probability that patients did not experience disease relapse, 6-months post start of treatment.

Probability that patients did not experience disease relapse, 12 months post treatment.

Probability that patients did not experience disease relapse, 24-months post start of treatment.

The length of time from the start of treatment that patients remain alive.

The probability that patients remain alive.

Checkmate Pharmaceuticals

Diwakar Davar

Assistant Professor

Adverse Events: Grade 1 and Grade 2 events per CTCAE v4.0 Serious Adverse Events: Grade 3 and Grade 4 events per CTCAE v4.0

Nivolumab and CMP-001 Combination

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Stage III melanoma, also known as regional melanoma, has metastasized (spread) to nearby lymph nodes, lymph vessels, or skin.

IIIB: tumor is up to 1.0 millimeter thick with or without broken skin (ulceration) or more than 1.0 millimeter and less than 2.0 millimeters IIIC: tumor is up to 2.0 millimeters thick with or without broken skin (ulceration) or more than 2.0 millimeters and less than 4.0 millimeters thick without IIID: tumor is more than 4 millimeters thick with broken skin (ulceration)

Disease Stage

All study-eligible patients assigned to treatment arm

Barbara Stadterman, MPH, MCCR; CRS Regulatory Supervisor

Patients who completed pre-operative therapy and receive surgery were evaluable for MPR; patients who did not undergo surgery for reasons of disease progression precluding surgery (rapid disease progression) were not evaluable

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Hematologic Cancer	NCT00039676	Waldenstrom Mac... Chronic Lymphoc... Hodgkin Disease NonHodgkin Lymp... Mixed Lymphopro...		11 Months -	National Institutes of Health Clinical Center (CC)
Identification of Surgical Management of Lymph Node Basins and Surgical Practice Patterns Among Sarcoma Surgeons	NCT04553744	Soft Tissue Sar... Lymph Node Canc...	Survey Administ...	18 Years -	M.D. Anderson Cancer Center
CMP-001 in Combo With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease	NCT03618641	Melanoma Lymph Node Canc...	CMP-001 Nivolumab	18 Years -	University of Pittsburgh
Identification of Surgical Management of Lymph Node Basins and Surgical Practice Patterns Among Sarcoma Surgeons	NCT04553744	Soft Tissue Sar... Lymph Node Canc...	Survey Administ...	18 Years -	M.D. Anderson Cancer Center
CMP-001 in Combo With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease	NCT03618641	Melanoma Lymph Node Canc...	CMP-001 Nivolumab	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for lymph node cancer