Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Bortezomib

Etoposide phosphate

Antineoplastic Agents, Immunological

Immunologic Factors

Combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B)

At the beginning of part C patients are randomized to receive bortezomib maintenance or observation without bortezomib.

Rituximab is given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and bortezomib every 3 weeks for 6 cycles.

Rituximab (R)

EPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles.

EPOCH

Bortezomib (B)

Bortezomib is given with EPOCH and rituximab every 6 weeks for 12 cycles.

At the beginning of Part C, patients are randomized to receive bortezomib maintenance or be observed w/o bortezomib.

Bortezomib or observation

Wyndham H Wilson, M.D.

This study will evaluate the effectiveness of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin-rituximab (EPOCH-R) chemotherapy plus bortezomib for treating mantle cell lymphoma, a cancer of white blood cells called lymphocytes. EPOCH-R consists of the drugs prednisone, etoposide, doxorubicin and vincristine, with the addition of a new drug called rituximab. In a recent study of patients with newly diagnosed mantle cell lymphoma, 92 percent had a complete remission of their disease after treatment with EPOCH-R. This study will test whether adding bortezomib as "maintenance therapy" once chemotherapy is finished will lengthen the time before the disease relapses and improve the overall cure rate.

Patients 18 years of age and older with mantle cell lymphoma may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, multi-gated acquisition scan (MUGA) or echocardiogram, imaging studies and biopsy to determine the extent of disease, and possible colonoscopy.

Participants undergo treatment in three parts, as follows:

* Part 1: Bortezomib alone: Patients receive 4 doses of bortezomib over 3 weeks. The drug is injected into a vein over about 30 seconds.
* Part 2: EPOCH-R chemotherapy plus bortezomib: This phase of treatment begins 3 to 4 weeks after completing Part 1. Treatment is given on an outpatient basis in six 3-week cycles, with all drugs administered over the first 5 days of each cycle. Patients take prednisone by mouth on days 1 to 5 and etoposide, doxorubicin, and vincristine as a 96-hour infusion through a vein over days 1 to 5. The infused drugs are delivered through a lightweight, portable infusion pump. Rituximab is given by vein over several hours on day 1 immediately before the chemotherapy infusion begins. Bortezomib is given by vein over 30 seconds on day 1 before the rituximab and again on day 4. Cyclophosphamide is given by vein over about 15 minutes on day 5 immediately after the chemotherapy infusion is completed. Patients are taught how to self inject granulocyte colony stimulating factor (G-CSF), a drug that helps boost white cell counts after chemotherapy. They inject the drug under the skin (like an insulin shot) for 10 days of each cycle beginning day 6. Patients also take an antibiotic to help prevent infection during chemotherapy.
* Part 3: Bortezomib alone: After completing EPOCH-R-B therapy, patients are randomly assigned to receive or not to receive bortezomib alone. The drug is given in 2 doses over 5 days, with a break of 16 days before the next dose. These 3-week cycles continue for up to 18 months or until the disease comes back or worsens. Patients who are assigned to the group that does not receive bortezomib will be offered the drug if their disease relapses.

During therapy, patients have tests performed on their bone marrow, tumor tissue, blood or other fluids to look at different genes and proteins that may be involved in the development of their lymphoma or the reaction of the immune system. A tissue biopsy is done before treatment begins and a day after treatment starts. Disease progress is followed with computed tomography (CT) scans and blood tests. When treatment is completed, patients whose cancer has disappeared are scheduled for periodic follow-up examinations and tests. Those whose disease remains or recurs may be offered participation in another protocol if an appropriate one is available or are returned to the care of their local physician.

...

Background:

Mantle cell lymphoma (MCL) presents a clinical challenge because it is aggressive and incurable with chemotherapy. Therefore novel treatment approaches are needed.

MCL has overexpression of NF-kappa B (NF-kappa B), a transcription factor that affects cell growth and survival, and cyclin D1 that affects cell cycle and growth. These proteins appear to be involved in the pathogenesis of MCL.

Bortezomib, a proteasome inhibitor that inhibits NF-kappa B and cyclin D1, has demonstrated activity in patients with relapsed or refractory MCL.

Dose-adjusted-etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin-rituximab (EPOCH-R) has excellent activity in MCL, with a complete response (CR) rate of 92%, but patients eventually relapse.

Objective:

Determine the progression free survival (PFS) and overall survival (OS) of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab,bortezomib (DA-EPOCH-RB) followed by bortezomib maintenance versus observation.

Eligibility:

Diagnosis of mantle cell lymphoma.

No prior treatment except for local radiation or a short course of steroids for control of symptoms,

Age greater than or equal to 18 years old.

Adequate major organ function unless impairment is due to lymphoma.

Study Design:

To assess the clinical activity and biological effects of bortezomib, patients will initially receive one cycle of bortezomib alone with sequential tumor biopsies for microarray analysis.

All patients will then receive Dose-adjusted (DA)-EPOCH-RB for 6 cycles, and if they have at least a PR, this will be followed by randomization to either immediate bortezomib maintenance x 18 months, or to observation, followed by bortezomib if progression occurs. This study has as a primary goal, to describe progression free survival (PFS) and overall survival of early bortezomib maintenance versus observation following induction with bortezomib followed by DA-EPOCH-RB. Important secondary goals are to assess response and toxicity to bortezomib alone or DA-EPOCH-RB, to evaluate time to progression after receiving bortezomib following progression on an observation arm, and to assess the biological effects of bortezomib on untreated MCL.

EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma

Randomized Phase II Study of Dose-Adjusted EPOCH-Rituximab-Bortezomib (EPOCH-R-B) Induction Followed by Bortezomib Maintenance Versus Observation in Untreated Mantle Cell Lymphoma With Microarray Profiling and Proteomics

Time interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes.The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.

Overall Survival is the time between the first day of treatment to the day of death. The primary evaluation will be a Kaplan-Meier analysis with a two tailed log rank test.

Time interval from start of treatment to documented evidence of disease progression. Progression is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes, appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, appearance of new palpable hepatomegaly or splenomegaly that was not previously present, and ≥50% increase in the absolute number of circulating lymphocytes.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Clinical response is assessed by the response criteria for lymphomas and is defined as a fraction of patients who have a complete response (CR) or a complete response (CR) + partial response (PR). A complete response is disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g. lactate dehydrogenase) definitely assignable to the lymphoma. Partial response is ≥50% decreased in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Progressive disease is defined by at least one of the following: ≥50% increase in the sum of the products of at least two lymph nodes appearance of new lymph nodes, ≥50% increase in the size of the liver and/or spleen, ≥50% increase in the absolute number of circulating lymphocytes.

National Cancer Institute (NCI)

Principal Investigator

Participants are grouped together in one arm/group because most adverse events occurred during Part B, in which all participants received drug.

Combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B)

Rituximab (R): Rituximab is given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and bortezomib every 3 weeks for 6 cycles.

EPOCH: EPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles.

Bortezomib (B): Bortezomib is given alone for one cycle.

EPOCH-R+Bortezomib

All Participants who received at least one dose of Bortezomib alone followed by EPOCH-R+B chemotherapy.

Bortezomib (B): Bortezomib is given alone for one cycle.

Combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B)

Rituximab (R): Rituximab is given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and bortezomib every 3 weeks for 6 cycles.

EPOCH: EPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles.

Bortezomib (B): Bortezomib is given alone for one cycle. Bortezomib or observation: At the beginning of Part C, patients are randomized to receive bortezomib maintenance or be observed w/o bortezomib.

All Participants

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Wyndham Wilson

Bortezomib maintenance

Bortezomib: Bortezomib is given with EPOCH and rituximab every 3 weeks for 6 cycles.

Bortezomib Maintenance

Observation

Twenty-three patients were not randomized. Sixteen due to neuropathy and seven due to "other" reasons.

Not Randomized

Progression Free Survival (PFS)

Median Overall Survival (OS)

Overall Progression Free Survival

Overall Survival

Count of Participants With Serious and Non-Serious Adverse Events

Overall Response (CR+PR)

Complete Response

Stable Disease

Progressive Disease

Not Evaluable

Participants are grouped together in one arm/group because this is the arm/group in which all participants received drug.

Clinical Response

Bortezomib is given alone for one cycle, then combo chemo etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-Rituxan (R) + Bortezomib (B) is given every 3 weeks for 6 cycles.

Bortezomib Then Bortezomib + DA-EPOCH-R Induction

Bortezomib alone is given in 3 week cycles. 3-week cycles continue up to 18 months or until the disease comes back or worsens.

Participants are observed without treatment.

Bortezomib Then Bortezomib + Induction

Screening for Randomization

Randomization

Heart and Blood Diseases

Symptoms and General Pathology

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Monoclonal Gammopathy of Undetermined Significance

Smoldering Multiple Myeloma

Paraproteinemias

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Hypergammaglobulinemia

Precancerous Conditions

patients with either Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM)

Mark J Roschewski, M.D.

Background:

- Multiple myeloma is a type of cancer that affects white blood cells and has a poor long-term survival rate. Two other types of cancer, monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM), may eventually progress and develop into multiple myeloma. Researchers are interested in collecting samples from individuals who have been diagnosed with MGUS and SMM to study possible risk factors for developing multiple myeloma.

Objectives:

- To study risk factors that may cause MGUS and SMM to progress to multiple myeloma.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with either MGUS or SMM but do not have multiple myeloma.

Design:

* Participants will be examined by study researchers at the initial visit, at 6 months following enrollment, and every 12 months for a maximum of 5 years.
* The following tests may be performed: (1) blood and urine tests, (2) bone marrow aspiration and biopsy, (3) imaging studies, and (4) a skeletal survey (a series of skeletal X-rays of the skull, spine, pelvis, ribs, shoulders, upper arm, and thigh bones).
* Treatment will not be provided as part of this protocol. - Participants will remain on the study for 5 years, or until their MGUS or SMM progresses to multiple myeloma requiring treatment.

Background:

* Multiple Myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3-4 years.
* Monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) are premalignant plasma cell proliferative disorders characterized by elevated monoclonal protein and bone marrow plasma cells. MGUS affects 3.2% of Caucasians over the age of 50 and has a 1% annual risk of progression to MM. approximately 3000 cases of SMM are diagnosed annually with a 10% annual risk of progression to MM.
* Current risk stratification schemes rely on serum protein markers and phenotyping by flow cytometry. While they can differentiate high and low risk patients, they cannot predict outcome for individual patients, are not integrated with one another, and have limited direct correlation to biology.
* Paired samples linked to clinical information can advance research into improved risk stratification, the pathogenesis of MGUS, SMM, and MM, and the potential for an early treatment window for these incurable diseases.

Objectives:

* To characterize the natural history and prognosis of MGUS and SMM
* To integrate protein markers (including immunoglobulin free light-chains) and immunophenotyping by flow cytometry with molecular profiles (including gene expression profiles) and clinical outcomes
* To apply expertise and diagnostic technology to provide improved evaluation, monitoring, and risk-stratification for patients on this protocol
* To provide paired samples of blood and tissue linked to clinical and molecular information for pilot translational studies

Eligibility:

* A confirmed diagnosis of MGUS or SMM (based on IMWG diagnostic criteria)
* Age greater than or equal to 18 years
* ECOG performance status in the range of 0-2
* Patients who have a diagnosis of MM are not eligible for this study.

Design:

* This is a prospective cohort study of patients with either MGUS or SMM.
* Following initial evaluation and confirmation of diagnosis, patients will be followed as clinically indicated, usually at 12 month intervals.
* The primary endpoint is progression to MM requiring treatment.
* Patients may donate cellular products or tissues as appropriate for research purposes.

  154 patients with MGUS and 154 patients with SMM will be enrolled on this protocol.

Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM)

determination of subtypes of MM based on GEP, and determination of prognostic indicators

comparison of molecular profiles and rate of disease progression per MM subtype

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma	NCT00114738	Lymphoma, Mantl... Mantle Cell Lym...	Rituximab (R) EPOCH Bortezomib (B) Bortezomib Bortezomib or o...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma	NCT00114738	Lymphoma, Mantl... Mantle Cell Lym...	Rituximab (R) EPOCH Bortezomib (B) Bortezomib Bortezomib or o...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM)	NCT01109407	Smoldering Myel... Monoclonal Gamm...		18 Years -	National Institutes of Health Clinical Center (CC)

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