A Randomized Clinical Trial of Lenalidomide (CC-5013) and Dexamethasone With and Without Autologous Peripheral Blood Stem Cell Transplant in Patients With Newly Diagnosed Multiple Myeloma
- Subjects must have histologically or cytologically confirmed Multiple Myeloma,
Salmon-Durie Stage II or III or International Staging System II or III that has not
been previously treated. (See Appendix E)
- Bone marrow plasmacytosis with > or = 10% plasma cells, or sheets of plasma cells or
a biopsy-proven plasmacytoma which must be obtained up to 6 weeks prior to
- Measurable levels of monoclonal protein (M protein): 1 g/dL IgG or .5 g/dL IgA on
serum protein electrophoresis or > 200 mg of monoclonal light chain on a 24 hour
urine protein electrophoresis which must be obtained within 4 weeks prior to
registration. If both serum and urine monoclonal components are present, both must
be followed in order to evaluate response.
Serum free light chains (FLC) should be measured with each SPEP and is recommended to
monitor for subjects with light chain disease. Non-secretory MM subjects will be included
if they have measurable parameters to follow, e.g. extramedullary plasmocytoma or
measurable bone marrow infiltration, or FLC level ≥ 10 mg/dL (≥ 100 mg/L) provided serum
FLC ratio is abnormal.29 Both SPEP and UPEP must be performed within 28 days prior to
registration. For subjects presenting with aggressive disease or requiring immediate
intervention, up to two weeks or two pulses of high dose dexamethasone (40 mg x 4 days = 1
pulse) is allowed, prior to the start of study treatment. If dexamethasone is given at
reduced dose, the total allowed dose is 320 mg prior to enrollment. Prior systemic
glucocorticosteroid use for the treatment of non-malignant disorders is permitted;
concurrent use after subject is on study treatment of non-malignant disorders is
permitted; concurrent use for non-malignant disorders after a subject is on study
treatment is permitted, but should be restricted to the equivalent of prednisone 10mg per
day. Prior or concurrent topical or localized glucocorticosteroid therapy to treat
non-malignant comorbid disorders is permitted.
Subjects should not have received any radiation for the preceding 4 weeks before entry
onto the study. Exception: local radiation therapy for symptomatic bone lesions (eg,
uncontrolled pain or high risk of pathologic fracture), superior or inferior vena cava
syndrome, spinal cord compression or extramedullary soft tissue lesions, as clinically
indicated to relieve severe symptoms. Subjects with prior solitary plasmacytoma treated
with radiation therapy with curative intent are eligible if the disease has now progressed
to active multiple myeloma meeting all the eligibility criteria for this protocol.
- Age >18 years.
- Life expectancy of greater than 12 months.
- ECOG performance status <2 (Karnofsky >60%) (See Appendix B).
- Subjects must have adequate organ and marrow function as defined below, obtained
within 4 weeks prior to registration:
Hgb > 9 g/dL (which may be supported by transfusion or growth factors) Absolute Neutrophil
Count >1,500/ ml (use of growth factors to meet screening requirements is not permitted)
Platelets >50,000/mm3 (administration of platelet transfusions during screening to meet
eligibility criteria is not allowed. However, platelet transfusions may be administered
as clinically indicated to subjects in both treatment arms who have begun lenalidomide
therapy) Total Bilirubin <1.5 mg/dL AST(SGOT) / ALT(SGPT) <2.5 X institutional upper limit
of normal Creatinine <2.0 mg/dL (subjects with creatinine > 2 should receive lenalidomide
according to the dosing schedule (Appendix C).
Creatinine Clearance >50 ml/min (estimated). Subjects with creatinine clearance < 50
ml/min should receive lenalidomide according to the dosing schedule (Appendix C).
- Ability to understand and the willingness to sign a written informed consent
document. Subject must be informed of the investigational nature of this study.
- Subjects with a history of prior malignancy are eligible provided there is no active
malignancy and a low expectation of recurrence within 6 months.
- Subjects must be willing and able to take prophylaxis with either aspirin at 81
mg/day or alternative prophylaxis with either low molecular weight heparin or
warfarin as recommended.
- Subjects who are eligible for transplant with an age up to and including 75 years.
- Subjects in ARM A who are refusing transplant can go onto ARM B and will be evaluated
- All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.
- 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 (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 28 days before
she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
Males must agree to use a latex condom during sexual contact with a FCBP even if they
have had a successful vasectomy. (See Appendix D: Risks of Fetal Exposure, Pregnancy
Testing Guidelines and Acceptable Birth Control Methods)
- Patients who have had chemotherapy or radiotherapy for multiple myeloma prior to
entering the study. Patients should not have received any radiation for the preceding
4 weeks before entry onto the study. Exception: local radiation therapy for
symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic
fracture), superior or inferior vena cava syndrome, spinal cord compression or
extramedullary soft tissue lesions, as clinically indicated to relieve severe
symptoms. Patients with prior solitary plasmacytoma treated with radiation therapy
with curative intent are eligible if the disease has now progressed to active
multiple myeloma meeting all the eligibility criteria for this protocol.
- Patients receiving any other investigational agents or therapy within 28 days of
- Patients with known brain metastases will be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
- Patients who are pregnant or breast feeding. Due to the potential teratogenic
properties of lenalidomide, the use of this drug in patients that are pregnant is
absolutely contraindicated. Further, all women of childbearing potentialFCBP and
sexually active males must agree to avoid conception while participating in this
study. Specifically, women of childbearing potentialFCBP must either agree to refrain
from sexual intercourse or employ a dual method of contraception, one of which is
highly effective (IUD, birth control pills, tubal ligation or partners vasectomy),
and another additional method (condom, diaphragm, or cervical cap) for 4 weeks prior
to receiving lenalidomide, and for four weeks after discontinuing this therapy.
Sexually active males cannot participate unless they agree to use a condom (even if
they have undergone a prior vasectomy) while having intercourse with a woman of child
bearing potentialFCBP while taking lenalidomide and for four weeks after stopping
treatment. Women of child bearing potentialFCBP (those who have not had a
hysterectomy or the absence of menstrual periods for at least 24 consecutive months)
must have a negative pregnancy test 10-14 days prior to the initiation of therapy and
a repeat negative pregnancy test 24 hours prior to the initiation of lenalidomide.
- Inability to comply with study and/or follow-up procedures.
- Patients with a history of previous deep vein thrombosisDVT or pulmonary embolismPE
must be on anticoagulation therapy with low molecular weight heparin or warfarin at
therapeutic dosages (e.g. INR 2-3).
- If a patient is on full-dose anticoagulants, the following criteria should be met for
- Must not have active bleeding or pathological conditions that carry high risk of
bleeding (e.g. tumor involving major vessels, known varices).
- Must not have thrombocytopenia requiring transfusion.
- Must have a platelet count >50,000.
- Must have stable INR between 2-3.
- Patients with smoldering myeloma or monoclonal gammopathy of undetermined
significance (MGUS) are not eligible.
- Patients must not have active, uncontrolled infection.
- Patients must not have active, uncontrolled seizure disorder. Patients must have had
no seizures in the last 6 months.
- Concurrent use of other anti-cancer agents or treatments.
- Known positive for HIV or infectious hepatitis, type B or C.
- Known hypersensitivity to thalidomide.
- 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.