Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide for Relapsed/Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: DVD-R
Intervention description: 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
Intervention MeSH terms: Lenalidomide; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: multiple myeloma; refractory; relapsed; bortezomib; doxil

Summary:

      This is a phase II, multicenter, open label, nonrandomized study to evaluate the efficacy and
      safety of lenalidomide at a dose of 10 mg/dose in combination with bortezomib at 1.0
      mg/m2/dose, pegylated liposomal doxorubicin (PLD) at 4.0 mg/m2/dose, and intravenous (IV)
      dexamethasone at 40 mg/dose in adult patients with relapsed/refractory multiple myeloma (MM).
      The study consists of a screening period, followed by up to eight 28 day open label treatment
      cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a
      follow-up period.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Has a diagnosis of multiple myeloma (MM) based on standard criteria (Durie 1986)

          2. Currently has MM with measurable disease (serum m protein > 1.0g/dl and/or 24 hr urine
             m protein > 200mg/24 hr)

          3. Currently has progressive MM that has relapsed or is refractory

          4. Voluntarily signed an informed consent

          5. Age 18 years

          6. Eastern Cooperative Oncology Group (ECOG) performance < 2

          7. Life-expectancy > 3 months

          8. Laboratory test results within these ranges:

               -  Absolute neutrophil count (ANC) 1.5 x 109/L; if the bone marrow is extensively
                  infiltrated (> 70% plasma cells) then 1.0 x 109/L

               -  Platelet count 75 x 109/L; if the bone marrow is extensively infiltrated (> 70%
                  plasma cells) then 50 x 109/L

               -  Hg > 8 g/dL

               -  Calculated or measured creatinine clearance > 30 mL/minute.

               -  Total bilirubin 2.0 x upper limit of normal (ULN)

               -  Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and
                  alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) 3 x ULN
                  or 5 x ULN if hepatic metastases are present

               -  Serum potassium within the normal range

          9. Disease free of prior malignancies for 5 years with exception of currently treated
             basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
             or breast

         10. Registered into the mandatory RevAssist® program, willing and able to comply with the
             requirements of RevAssist®.

         11. Females of childbearing potential must have a negative serum or urine pregnancy test
             and must either commit to continued abstinence from heterosexual intercourse or begin
             TWO acceptable methods of birth control.

         12. 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)

        Exclusion Criteria:

          1. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal
             protein and skin changes syndrome

          2. Plasma cell leukemia

          3. Grade 2 peripheral neuropathy within 14 days before enrollment

          4. Impaired cardiac function or clinically significant cardiac diseases, including
             myocardial infarction within 6 months prior to enrollment, New York Heart Association
             (NYHA) Class II or greater heart failure, Uncontrolled angina, clinically significant
             pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or
             Multigated acquisition(MUGA) scan evidence of left ventricular ejection fraction
             (LVEF) below institutional normal within 28 days prior to enrollment,
             electrocardiographic (ECG) evidence of acute ischemia or active conduction system
             abnormalities. Prior to study entry, any ECG abnormality at Screening has to be
             documented by the investigator as not medically relevant.

          5. Severe hypercalcemia, i.e., serum calcium 12 mg/dL (3.0 mmol/L) corrected for albumin

          6. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form

          7. Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study

          8. Undergone major surgery within 28 days prior enrollment or has not recovered from side
             effects of such therapy (Kyphoplasty is not considered to be a major surgery; however,
             the investigator is to discuss enrollment of a patient with a recent history of
             kyphoplasty with the medical monitor).

          9. Pregnant or breast feeding females. (Lactating females must agree not to breast feed
             while taking lenalidomide)

         10. Received the following prior therapy:

               -  Chemotherapy within 3 weeks of enrollment (6 wks for nitrosoureas)

               -  Corticosteroids (>10 mg/day prednisone or equivalent) within 3 weeks of
                  enrollment

               -  Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic
                  trioxide or bortezomib within 21 days before enrollment

               -  Radiation therapy within 28 days before enrollment, except localized radiation
                  therapy

               -  Use of any other experimental drug or therapy within 28 days of enrollment

         11. Known hypersensitivity to compounds of similar to thalidomide, doxorubicin,
             bortezomib, boron or mannitol.

         12. The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs

         13. Concurrent use of other anti-cancer agents or treatments

         14. Known positivity for human immunodeficiency virus (HIV) or hepatitis B or C; baseline
             testing for HIV and hepatitis B or C is not required