Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma

Leukemia

Leukemia, Lymphoid

Lymphoma, Non-Hodgkin

Hematologic Neoplasms

Influenza, Human

Pneumonia

Leukemia, Lymphocytic, Chronic, B-Cell

Monoclonal Gammopathy of Undetermined Significance

Lymphocytosis

Lymphoma, B-Cell

Smoldering Multiple Myeloma

Waldenstrom Macroglobulinemia

Paraproteinemias

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Blood Protein Disorders

Hemorrhagic Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Hypergammaglobulinemia

Leukocytosis

Leukocyte Disorders

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

B-cell Lymphoma

All adult patients who are newly diagnosed at Aurora Health Care with the following B-Cell Hematologic Malignancies: Monoclonal gammopathy of undetermined significance (MGUS), Smoldering multiple myeloma (SMM), Multiple myeloma (MM), Waldenstroms Macroglobulinemia (WM), Monoclonal B-cell lymphocytosis (MBL), Chronic lymphocytic leukemia (CLL), or B-Cell Non-Hodgkin lymphoma (NHL).

Michael Thompson, MD, PhD

The goal of this study is to develop a vaccination registry system for Aurora Health Care patients newly diagnosed with MM and other B-Cell Hematologic Malignancies in order to prospectively characterize vaccination history and outcomes such as infection in these patients at Aurora Health Care. Additionally hospitalization rates, cost analysis, infection (influenza, pneumonia, other) related to vaccination in this patient population will be evaluated.

This is a prospective registry study on the immunizations in patients with B-Cell Hematologic Malignancies at Aurora Health Care. This observational study will consist of prospective medical record review of Aurora Health Care patients newly diagnosed B-Cell Hematologic Malignancies and will be used to characterize vaccination history, infection rate, and hospitalization rate. This is the second study in the series of studies designed to provide important information about the best way and time to vaccinate patients with MM and similar cancers to flu and pneumonia and to gather additional information about immune function in this patient population.

The registry will include all adult patients who are newly diagnosed with the following B-Cell Hematologic Malignancies: Monoclonal gammopathy of undetermined significance (MGUS), Smoldering multiple myeloma (SMM), Multiple myeloma (MM), Waldenstroms Macroglobulinemia (WM), Monoclonal B-cell lymphocytosis (MBL), Chronic lymphocytic leukemia (CLL), or B-Cell Non-Hodgkin lymphoma (NHL). The prevalence of newly diagnosed B-Cell Hematologic Malignancies at Aurora Health Care is approximately 1000 patients annually. This registry will be ongoing to collect real time data, with no definite sample size planned; however, data will be collected for at least 10 years. This time frame is based on Surveillance, Epidemiology, and End Results Program (SEER) data. There is a 50% survival rate at 5 years after diagnosis for MM, so the 10 year time frame will be able to capture long term outcome in patients.

Medical record information will be obtained through electronic data capture by Aurora Health Care staff with access to the electronic medical records. Data will be manually reviewed by the coordinator, Investigator and co-investigators for accuracy and completeness, to the extent available in the clinical medical record. Additionally, a biostatistician will assist in data analysis.

Descriptive statistics such as counts, proportions or percentages for category variables and mean and standard deviation for continuous variables will be computed for the all the variables. Depending upon the distribution of the category variables appropriate statistical tests such as chi-square and/or Fisher exact test will be used to find out the statistical significance. For continuous variables an appropriate statistical test such as t-tests and/or F test will be used.

This registry will be used for this research study, and may be queried for internal quality improvement projects as well. The principal investigator will be responsible for the overall monitoring of the data and safety of study participants/data integrity, with the assistance of other study team members.

B-Cell Hematologic Malignancy Vaccination Registry

Information regarding vaccination history will be collected historically and throughout data collection, expected to continue for about 10 years.

Survival status will be collected throughout data collection, expected to continue for about 10 years.

Information about any infections (influenza, pneumonia, other) such as numbers, types will be collected throughout data collection, expected to continue for about 10 years.

Information regarding hospitalization will be collected throughout data collection, expected to continue for about 10 years.

Vince Lombardi Cancer Clinic

Michael A. Thompson, MD, PhD

Hematologist/Oncologist; Medical Director of Early Phase Cancer Research

Wounds and Injuries

Syndrome

Recurrence

Fatigue

Communicable Diseases

Body Weight

Neoplasm Metastasis

Anemia

Thrombocytopenia

Weight Loss

Hyperthermia

Lymphadenopathy

Fever

Leukemia, Prolymphocytic

Body Weight Changes

Blood Platelet Disorders

Cytopenia

Richter Syndrome

Patients receive infusion of ex vivo-activated autologous lymph node lymphocytes IV over 10-30 minutes on day 0.

Ex Vivo-activated Autologous Lymph Node Lymphocytes

Laboratory Biomarker Analysis

Chitra Hosing

This phase II trial studies the side effects of ex vivo-activated autologous lymph node lymphocytes infusion and to see how well they work in treating patients with chronic lymphocytic leukemia. Biological therapies, such as ex vivo-activated autologous lymph node lymphocytes, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing.

PRIMARY OBJECTIVES:

I. To assess the feasibility and safety of infusion of autologous activated T-cells (ex vivo-activated autologous lymph node lymphocytes) in patients with chronic lymphocytic leukemia.

SECONDARY OBJECTIVES:

I. To study immune reconstitution following infusion of activated T-cells in patients with chronic lymphocytic leukemia.

II. To study the incidence of infections for up to 1 year following activated T cell infusion.

III. To study the overall response rates.

OUTLINE:

Patients receive infusion of ex vivo-activated autologous lymph node lymphocytes intravenously (IV) over 10-30 minutes on day 0.

Patients who have been previously treated on study, and subsequently need additional infusions, may be retreated with previously cryopreserved expanded cells at the same or lower dose level 6-12 months after the first infusion.

After completion of study treatment, patients are followed up at 1.5 years and then every 6 months for up to 5 years.

Ex Vivo-activated Autologous Lymph Node Lymphocytes in Treating Patients With Chronic Lymphocytic Leukemia

Trial of Immune Reconstitution With Activated T-Cells in Patients With Chronic Lymphocytic Leukemia (CLL)

Success will be defined as achievement of a target activated T-cell dose of 1x108 +/-20% without DLT and the lack of dose limiting toxicity (DLT). DLT for this trial is defined as any Grade 4 or higher non-hematologic toxicity or grade 3 or 4 allergy/immunology toxicity, allergic reaction or urticaria grade 3 or higher by +90 days after T cell infusion, Grade 2 or greater autoimmune phenomena, or Grade 4 or higher hematologic toxicity (with the exception of any preexisting AE due to prior treatment or due to disease) deemed related to T cells and occurring by day +90 after T cell infusion. Feasibility is defined as achievement of the target T-cell dose (1x108 +/-20% ) without DLT in \>50% of patients enrolled.

To study immune reconstitution following infusion of activated T-cells in patients with chronic lymphocytic leukemia

The overall response rates between the lenalidomide and non-lenalidomide arms. For response to treatment, it was measured by International Workshop on CLL (iwCLL), criteria 2008 guidelines.

To study the incidence of infections for up to 1 year following activated T cell infusion

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Patients who qualify for lymphodepleting chemotherapy and who do not have 17p deletion are randomized to Arm A or Arm B. Those patients who do not qualify by those criteria are assigned to Arm C.

Receive lymphodepletion chemotherapy followed by activated T-cell infusion

Arm A

Receive lymphodepletion chemotherapy followed by activated T-cell infusion followed by low dose lenalidomide PO once ANC is\>1.5x109/L

Arm B

Patients who cannot receive lymphodepleting chemotherapy (as determined by the treating physician) or those with 17p deletion

Arm C

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

All patients were enrolled in Arm C at the physician's discretion and there is no analysis to compare between the lenalidomide Arm A vs the non-lenalidomide Arm B

Dr. Chitra Hosing / Stem Cell Transplantation

Sucessful Target T-cell Dose

Feasibility

Treatment Success and Feasibility of Autologous Activated T-cells Infusion, Determined by Number of Participants That Achieved Target-Activated T-cell Dose Without DLT.

Data was not collected due to low accrual

Immune Reconstitution

Overall Response Rates

Incidence of Infections

Overall Study

Splenomegaly

Hypertrophy

Pathological Conditions, Anatomical

Hypoglycemic Agents

All Drugs and Chemicals

Anti-Infective Agents

Metformin

Ritonavir

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Cytochrome P-450 CYP3A Inhibitors

Cytochrome P-450 Enzyme Inhibitors

SINGLE AGENT STAGE : Patients receive metformin hydrochloride PO BID on days 1-7 in the absence of disease progression or unacceptable toxicity.

COMBINATION REGIMEN STAGE: Patients receive metformin hydrochloride PO BID and ritonavir orally PO BID on days 1-7. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Metformin Hydrochloride

Pharmacological Study

Quality-of-Life

Questionnaire

Nitya Nathwani, MD

This pilot clinical trial studies the side effects and best dose of metformin hydrochloride and ritonavir in treating patients with multiple myeloma or chronic lymphocytic leukemia that has returned after a period of improvement or has not responded to treatment. Metformin hydrochloride and ritonavir may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To assess the safety, tolerability and feasibility of administering metformin hydrochloride (metformin)/ritonavir combination therapy in patients with relapsed/refractory multiple myeloma or relapsed/refractory chronic lymphocytic leukemia.

SECONDARY OBJECTIVES:

I. To characterize the clinical activity of this two-drug combination by assessing disease response, response duration, and (in relapsed/refractory multiple myeloma \[RRMM\]) clinical benefit response.

II. To assess the progression-free survival, overall survival and compliance of all patients who start the two-drug combination.

III. To evaluate potential changes in health-related quality of life, as assessed by the Functional Assessment of Cancer Therapy for Multiple Myeloma (FACT-MM) and Leukemia (FACT-Leu).

TERTIARY OBJECTIVES:

I. To describe the plasma pharmacokinetics of metformin and ritonavir when given in combination.

II. In relapsed/refractory chronic lymphocytic leukemia (RRCLL), to describe changes in pAKT, pAMPK, and MCL-1, in circulating lymphocytes in response to treatment.

OUTLINE: This is a dose escalation study.

SINGLE AGENT STAGE: Patients receive metformin hydrochloride orally (PO) twice daily (BID) on days 1-7 in the absence of disease progression or unacceptable toxicity.

COMBINATION REGIMEN STAGE: Patients receive metformin hydrochloride PO BID and ritonavir PO BID on days 1-7. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 28 days.

Metformin Hydrochloride and Ritonavir in Treating Patients With Relapsed or Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia

A Pilot Feasibility Study of Metformin/Ritonavir Combination Treatment in Patients With Relapsed/Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia

Observed toxicities will be summarized, for all patients based on highest achievable dose, in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

Will be categorized using International Myeloma Working Group (IMWG). Will be calculated, for the initial and sub-analysis for all dose levels; Copper Pearson binomial 95% confidence intervals will be calculated for these estimates. Will be evaluated based on number/type of prior therapy(ies).

Will be categorized using IMWG. Clopper Pearson binomial 95% confidence intervals will be calculated. Will be evaluated based on number/type of prior therapy(ies).

The Functional Assessment of Cancer Therapy for Multiple Myeloma and Leukemia will be scored using published guidelines.

Will be estimated using the product limit method of Kaplan Meier.

First documented response is defined as stringent complete response, complete response, very good partial response, or partial response.

Will be categorized using IMWG. Will be estimated using the product limit method of Kaplan Meier.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
B-Cell Hematologic Malignancy Vaccination Registry	NCT02298816	Monoclonal Gamm... Multiple Myelom... Waldenstrom Mac... Lymphocytosis Lymphoma, Non-H... B-Cell Chronic ... Hematological M...		-	Aurora Health Care
B-Cell Hematologic Malignancy Vaccination Registry	NCT02298816	Monoclonal Gamm... Multiple Myelom... Waldenstrom Mac... Lymphocytosis Lymphoma, Non-H... B-Cell Chronic ... Hematological M...		-	Aurora Health Care
Ex Vivo-activated Autologous Lymph Node Lymphocytes in Treating Patients With Chronic Lymphocytic Leukemia	NCT02530515	Anemia Cancer Fatigue Chronic Lymphoc... Fever Infectious Diso... Lymphadenopathy Lymphocytosis Night Sweats Prolymphocytic ... Recurrent Chron... Richter Syndrom... Secondary Malig... Thrombocytopeni... Weight Loss	Ex Vivo-activat... Laboratory Biom...	-	M.D. Anderson Cancer Center
Metformin Hydrochloride and Ritonavir in Treating Patients With Relapsed or Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia	NCT02948283	Anemia Fatigue Fever Lymphadenopathy Lymphocytosis Night Sweats Recurrent Chron... Recurrent Plasm... Refractory Chro... Refractory Plas... Splenomegaly Thrombocytopeni... Weight Loss	Laboratory Biom... Metformin Hydro... Pharmacological... Ritonavir Quality-of-Life Questionnaire	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for lymphocytosis