Lenalidomide Maintenance Therapy for Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Lenalidomide
Intervention description: 10 mg oral daily, on days 1-21 of repeated 28 day cycles, to continue until disease progression or unacceptable toxicity.
Intervention MeSH terms: Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: NK Cell Function; Immunomodulatory Drugs; T Cell Activity; Immune Stimulatory Effects; Extended Dosing

Summary:

      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.
    

Eligibility criteria:

        -  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