Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Lenalidomide

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.

Dickran Kazandijicn, M.D.

Background:

* Multiple myeloma is rarely curable, but it is treatable. Initial treatment is directed at controlling symptoms and reducing the number of myeloma cells. It continues until the cancer stops responding to treatment. At that time, treatment may switch to maintenance therapy, which is given to try to extend the response of the first therapy for as long as possible. Research suggests that lenalidomide maintenance therapy may delay the time for myeloma cells to start to grow and possibly improve survival.
* Lenalidomide is a drug that may reduce or prevent the growth of cancer cells. Researchers want to look at the long-term effect of lenalidomide on immune cells. It will also look at the effects of extended treatment on the cancer and the immune system.

Objectives:

- To test the long-term effectiveness of lenalidomide therapy for multiple myeloma.

Eligibility:

- Individuals at least 18 years of age with newly diagnosed or relapsed multiple myeloma.

Design:

* Participants will be screened with a physical exam and medical history. Blood and urine sample will be collected. A bone scan and bone marrow biopsy will also be performed.
* Participants will receive lenalidomide maintenance treatment. It will be given according to the standard of care for multiple myeloma. Participants will take lenalidomide every day for 21 days of repeated 28-day cycles.
* Treatment will be monitored with frequent blood tests. Blood tests will look at the effect of the treatment on the immune system.
* Treatment will continue as long as the cancer does not worsen and the side effects are not severe.

Background:

Multiple myeloma (MM) remains largely an incurable disease with an estimated median survival of 6-7 years in standard risk myeloma and 2-3 years in high risk disease despite treatment with autologous stem cell transplantation (ASCT).

Maintenance therapy to achieve sustained suppression of residual disease following chemotherapy or ASCT has long been viewed as a desirable approach for extending survival in MM.

Giving the immunomodulatory drug lenalidomide after induction or re-induction treatment may stimulate the immune system in various ways to stop or slow the return of cancer.

It is not yet known how immune stimulatory effects of extended dosing with lenalidomide in the maintenance setting correlate with clinical benefits.

Objectives:

Assess T cell (cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), natural killer T cell (NKT) and normal killer (NK) cell numbers in peripheral blood during the

course of lenalidomide maintenance therapy in treated MM patients.

Eligibility:

Patients with multiple myeloma who have achieved stable disease or better response, assessed at greater than or equal to 4 weeks after completing induction or re-induction treatment

Age greater than or equal to 18 years

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2

Adequate hematological parameters defined by: absolute neutrophil count greater than or equal to 1.0 K/microL, hemoglobin greater than or equal to 8 g/dL, and platelet count greater than or equal to 75 K/microL

Adequate hepatic function, with bilirubin \< 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 times ULN

Adequate renal function with creatinine clearance (CrCl) of greater than or equal to 40 mL/min. CrCl will be calculated using the Cockcroft-Gault method. If the calculated CrCl based on Cockcroft-Gault method is \<40 mL/min, patient will have a 24 hr urine collection to measure CrCl. The measured CrCl must also be greater than or equal to 40 ml/min

Design:

Single arm, single stage, phase II trial of lenalidomide maintenance for treated MM patients who have stable or responsive disease.

After screening, eligibility determination, and enrollment; subjects will receive lenalidomide 10 mg by mouth daily on days 1-21 of repeated 28-day cycles. When necessary, lenalidomide will be held and restarted in accordance with accepted clinical dose modification guidelines.

Subjects may continue lenalidomide until disease progression or unacceptable toxicity or completion of two years of lenalidomide therapy and the 30 day safety follow-up visit.

Blood will be obtained to assess changes in T cell (CD4, CD8), NKT and NK cell numbers by flow-cytometric analysis at pre-specified time points during lenalidomide maintenance.

Blood samples and/or bone marrow samples where possible, will be used for additional research studies, which may include functional analyses of immune-cell subsets, analyses for cytokines, chemokines, antibodies, tumor cell antigen targets, and/or other markers.

Lenalidomide Maintenance Therapy for Multiple Myeloma

Lenalidomide Maintenance Therapy in Multiple Myeloma: A Phase II Clinical and Biomarker Study

Peripheral blood samples will be collected to assess T cell (CD4, CD8), NKT and NK cell counts using flow cytometry.

Here is the number of 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.

Duration of response is defined as time from response to disease progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be \>10mg/dl.

PFS is defined as the time from study entry until progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be \>10mg/dl.

Percent change in total number of B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy

Relative fold change in CRBN and correlation (R2) to NK cell number and activity.

Celgene Corporation

National Cancer Institute (NCI)

Principal Investigator

10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.

Lenalidomide: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Not Hispanic

Mexican, Cuban, Puerto Rican, Central/So. American

Race/Ethnicity, Customized

United States

Region of Enrollment

Dr. Dickran Kazandijian

This outcome was not done because this study was closed prior to full enrollment. Given study closure, the primary endpoint could not be and was not evaluated. There was not an adequate amount of specimens collected to arrive to any analyses conclusions.

Longitudinal Assessment of T Cell (Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8), Natural Killer T-cell (NKT) and Natural Killer (NK) Cell Counts

Number of Participants With Serious and Non-serious Adverse Events

Duration of Response

Progression Free Survival (PFS)

Natural Killer (NK) Cell Function and Activity

Changes in B Cell Subsets, Myeloid Derived Suppressor Cells and T Regulatory Cells by Phenotypic Analysis During the Course of Therapy

Expression of Cereblon (CRBN) and How it Relates to Natural Killer (NK) Cell Number and Activity

Overall Study

Spots Global Cancer Trial Database for t cell activity