Phase II Study of Dexamethasone, Thalidomide and Lenalidomide for Subjects With Relapsed or Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: dexamethasone; thalidomide; lenalidomide
Intervention description: Cycles 1-4 • Dexamethasone (40mg ) will be given on days 1-4, 9-12, 17-20 of a 28-day cycle.
After completing 4 cycles:
Patients who demonstrate disease progression at any time will be taken off study.
Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for > 2 cycles will be transitioned to maintenance therapy.
Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for >2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.
Maintenance therapy will consist of:
• Dexamethasone 20mg weekly days 1, 8, 15, 22 out of a 28 day cycle); Cycles 1-4
• Thalidomide will be given 50mg daily on days 1-7, thereafter 100mg daily on days 8-28 of the first 28-day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 of each subsequent cycle.
After completing 4 cycles:
Patients who demonstrate disease progression at any time will be taken off study.
Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for > 2 cycles will be transitioned to maintenance therapy.
Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for >2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.; Cycles 1-4 • Lenalidomide will be given 25mg daily for days 1-21 of each 28 day cycle.
After completing 4 cycles:
Patients who demonstrate disease progression at any time will be taken off study.
Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for > 2 cycles will be transitioned to maintenance therapy.
Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for >2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.
Maintenance therapy will consist of:
• Lenalidomide 25 mg/daily days 1 - 21 out of a 28 day cycle. 15mg/daily on days 1-21 of a 28 day cycle of lenalidomide will be given to patients with a creatinine clearance of < 40cc/min*
Intervention MeSH terms: Thalidomide; Dexamethasone; Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: myeloma; relapsed or refractory multiple myeloma

Summary:

      Study Objectives

        1. To evaluate the efficacy of the combination of dexamethasone (Decadron®), thalidomide
           (Thalomid®), and lenalidomide (Revlimid®) as therapy for patients with relapsed or
           refractory multiple myeloma (MM) who have failed prior treatment with both lenalidomide
           and thalidomide when used as monotherapies.

        2. To evaluate the safety of the combination of lenalidomide, dexamethasone, and
           thalidomide as a therapy for patients with relapsed or refractory multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must voluntarily sign and understand written informed consent.

          -  Age > 18 years at the time of signing the consent form.

          -  Histologically confirmed Salmon-Durie stage II or III MM. Stage I MM patients will be
             eligible if they display poor prognostic factors (ß2M ≥5.5 mg/L, plasma cell
             proliferation index ≥5%, albumin of less then 3.0, and unfavorable cytogenetics).

          -  Relapsed or refractory myeloma as defined by Appendix II, table 1, progression of
             disease either after prior therapy or lack of response to currently used therapy.

          -  Prior treatment with prior lenalidomide and thalidomide as single agents or in
             combination with dexamethasone, but not in combination with each other.

          -  No anti-myeloma therapy within 14 days prior to initiation of study treatment.
             Patients may be receiving adjuvant antiresorptive therapy (i.e., pamidronate or
             zoledronic acid) as routine care.

          -  Measurable disease as defined by > 1.0 g/dL serum monoclonal protein, >0.1 g/dL serum
             free light chains, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable
             plasmacytoma(s).

          -  Karnofsky performance status ≥70% (>60% if due to bony involvement of myeloma.

          -  All study participants must be registered into the mandatory RevAssist® and
             S.T.E.P.S.® programs, and be willing and able to comply with the requirements of the
             RevAssist® and S.T.E.P.S.® programs.

          -  Females of childbearing potential (FCBP)† must have a negative serum or urine
             pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to
             and again within 24 hours of prescribing lenalidomide and thalidomide (prescriptions
             must be filled within 7 days) and must either commit to continued abstinence from
             heterosexual intercourse or begin TWO acceptable methods of birth control, one highly
             effective method and one additional effective method AT THE SAME TIME, at least 4
             weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy
             testing. Men must agree to use a latex condom during sexual contact with females of
             child bearing potential even if they have had a successful vasectomy.

          -  Able to take aspirin daily as prophylactic anticoagulation (patients intolerant to ASA
             may use warfarin or low molecular weight heparin).

          -  Life expectancy ≥ 3 months

          -  Subjects must meet the following laboratory parameters:

               -  Absolute neutrophil count (ANC) ≥1000 cells/mm3 (1.0 x 109/L)

               -  Platelets count ≥ 75,000/mm3 (75 x 109/L)

               -  Serum SGOT/AST <3.0 x upper limits of normal (ULN)

               -  Serum SGPT/ALT <3.0 x upper limits of normal (ULN)

               -  Serum creatinine <2.5 mg/dL (221 µmol/L)

               -  Serum total bilirubin <2.0 mg/dL (34 µmol/L)

        Exclusion Criteria:

          -  Patients with non-secretory MM (no measurable monoclonal protein, free light chains,
             and/or M-spike in blood or urine).

          -  Prior history of other malignancies (except for basal cell or squamous cell carcinoma
             of the skin or carcinoma in situ of the cervix or breast) unless disease free for ≥ 5
             years.

          -  Myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital
             Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled
             ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active
             conduction system abnormalities.

          -  Pregnant or lactating females are ineligible.

          -  Given the potential of the study drugs to trigger or worsen HIV viremia and the
             incidence of opportunistic infections inpatients infected with the HIV virus, HIV-1 or
             HIV-2 positive patients will be excluded. The interactions of HAART with study drugs
             have not been determined.

          -  Active hepatitis B or hepatitis C infection.

          -  Active viral or bacterial infections or any coexisting medical problem that would
             significantly increase the risks of this treatment program.

          -  Any coexisting medical problem or laboratory evaluation that, in the treating
             physician's or principal investigator's opinion, makes the patient unsuitable to
             participate in this clinical trial.

          -  Known hypersensitivity to dexamethasone, lenalidomide, or thalidomide.

          -  History of thromboembolic event within the past 6 months prior to enrollment.