Lenalidomide Maintenance Therapy for Multiple Myeloma
Lenalidomide Maintenance Therapy for Multiple Myeloma
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.
-  INCLUSION CRITERIA:

 -  Patients with multiple myeloma treated with induction therapy or re-induction therapy,
 who at the time of study enrollment have documented evidence of stable disease
 response or better according to International Myeloma Workshop Consensus Panel. The
 response assessment must occur at least 4 weeks after completion of their last
 treatment.

 -  Age greater than or equal to 18 years. Because no dosing or adverse event data are
 currently available on the use of lenalidomide in patients

 -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.

 -  Patient must have adequate hematologic, renal, hepatic, and cardiac function as
 defined by:

 -  Absolute neutrophil count greater than or equal to 1.0 K/microL independent of
 growth factor support

 -  Platelets greater than or equal to 75K/microL

 -  Hemoglobin greater than or equal to 8 g/dL (transfusions are permissible)

 -  Calculated creatinine (CrCl) clearance of greater than or equal to 40 mL/min.
 using the Cockcroft-Gault method. If the calculated CrCl based on Cockcroft-Gault
 method is

 -  Total bilirubin less than or equal to 1.5 mg/dL, aspartate aminotransferase
 (AST)/ serum glutamic oxaloacetic transaminase (SGOT) and alanine
 aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) less than or
 equal to 3 times ULN

 -  Females of childbearing potential (FCBP) must agree to use two effective forms of
 contraception simultaneously or to practice complete abstinence from heterosexual
 intercourse during the following time periods related to this study: 1) for at least
 28 days before starting study drug; 2) while participating in the study; and 3) for at
 least 28 days after discontinuation from the study. The two methods of effective
 contraception must include one highly effective method (i.e. intrauterine device
 (IUD), hormonal [birth control pills, injections, or implants], tubal ligation,
 partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom,
 diaphragm, cervical cap). FCBP must be referred to a qualified provider of
 contraceptive methods if needed.

 -  A FCBP is defined as a sexually mature woman who: 1) has not undergone a hysterectomy
 or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24
 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive
 months).

 -  A FCBP must have two negative serum or urine pregnancy tests prior to starting study
 drug. The first pregnancy test must be performed within 10-14 days prior to the start
 of study drug and the second pregnancy test must be performed within 24 hours prior to
 prescribing the study drug. The prescriptions of study drug must be filled within 7
 days.

 -  Male patients must agree to use a latex condom during sexual contact with FCBP while
 participating in the study and for at least 28 days following discontinuation from the
 study even if he has undergone a successful vasectomy.

 -  Patient must be able to take aspirin (81 or 325 mg) daily as prophylactic
 anticoagulation. Patients intolerant to acetylsalicylic acid (ASA) may use warfarin or
 low molecular weight heparin.

 -  Patient must understand and voluntarily sign an informed consent form, with the
 understanding that the patient may withdraw consent at any time without prejudice to
 future medical care.

 EXCLUSION CRITERIA:

 -  Patients with progressive or refractory multiple myeloma (MM), as defined by
 International Myeloma Workshop Consensus Panel criteria.

 -  Refractory to lenalidomide in the most recent line of therapy, as defined by the
 International Myeloma Consensus Panel criteria - as failure to achieve minimal
 response or development of progressive disease while on lenalidomide or within 30 days
 of lenalidomide therapy

 -  Patients who are receiving any other investigational agents with the intent to treat
 myeloma. Permitted concurrent therapies include:

 -  Bisphosphonates

 -  Radiotherapy to single stable disease site

 -  Plasma cell leukemia

 -  Pregnant or lactating females. Because there is a potential risk for adverse events to
 nursing infants secondary to treatment of the mother with lenalidomide, lactating
 females must agree not to breast feed while taking lenalidomide.

 -  Uncontrolled hypertension or diabetes

 -  Active hepatitis B or C infection

 -  Diagnosed or treated for another malignancy within 3 years prior to study enrollment,
 with the exception of complete resection of non-melanoma skin cancer, or an in situ
 malignancy

 -  Previous diagnosis of another malignancy with any evidence of residual disease.

 -  Patients seropositive for the human immunodeficiency virus (HIV), and/or those who are
 taking anti-retroviral treatment for HIV/acquired immune deficiency syndrome (AIDS)

 -  Prior organ transplant requiring immunosuppressive therapy

 -  Prior allogeneic stem cell transplant

 -  Patients requiring continuous, systemic immunosuppressive therapy

 -  Patients with myocardial infarction within 6 months prior to enrollment, New York
 Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
 uncontrolled cardiac arrhythmias, or electrocardiographic evidence of acute ischemia

 -  Patients with conditions that would prevent absorption of the study drug

 -  Uncontrolled intercurrent illness including but not limited to uncontrolled infection
 or psychiatric illness/social situations that would compromise compliance with study
 requirements

 -  Significant neuropathy greater than or equal to Grade 3 at baseline

 -  Contraindication to concomitant anticoagulation prophylaxis

 -  Major surgery within 1 month prior to enrollment

 -  Patients who were previously exposed and who developed severe adverse events,
 hypersensitivity or desquamating rash to either thalidomide or lenalidomide