Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This randomized phase III trial studies bortezomib, lenalidomide, and dexamethasone to see
how well they work compared to carfilzomib, lenalidomide, and dexamethasone in treating
patients with newly diagnosed multiple myeloma. Bortezomib and carfilzomib may stop the
growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide
may help the immune system kill abnormal blood cells or cancer cells. Drugs used in
chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer
cells, either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. It is not yet known whether bortezomib, lenalidomide, and dexamethasone are more
or less effective than carfilzomib, lenalidomide, and dexamethasone in treating patients with
multiple myeloma
Phase
Phase 3
Funding Agency/Sponsor
National Cooperative Group
Disease
Myeloma
Enrollment Eligibility
Inclusion Criteria:
- STEP I: Patients must be diagnosed with symptomatic standard-risk multiple myeloma
(SR-MM) as defined by all of the following (except gene expression profile [GEP]70
status if unknown):
- No evidence of t(14;16) by fluorescence in situ hybridization (FISH) testing on
bone marrow or not available
- No evidence of t(14:20) by FISH testing on bone marrow or not available
- No evidence of deletion 17p by FISH testing on bone marrow
- FISH should be from within 90 days of registration
- NOTE: If the FISH result states that no immunoglobulin heavy chain (IgH)
abnormality is present, both t(14;16) and t(14;20) can be considered
negative; in addition, if the patient has a t(11;14) or t(4;14)
translocation present, they can be considered negative for t(14;16) and
t(14;20); if testing for t(14;16) or t(14;20) could not be performed for
lack of sufficient material or non-availability of the probe in the test
panel, patients can be enrolled on the study
- Standard Risk GEP70 signature within the past 90 days (only if GEP has been done
and results are available)
- NOTE: GEP testing is NOT a requirement for the study; if the test has been
done, patients found to have a GEP70 status of high-risk will not be
eligible
- Serum lactate dehydrogenase (LDH) =< 2 x upper limit of normal (ULN) within the
past 28 days
- No more than 20% circulating plasma cells on peripheral blood smear differential
or 2,000 plasma cells/microliter on white blood cell (WBC) differential of
peripheral blood within the past 90 days
- NOTE: This is NOT the plasma cell % from the marrow aspirate
- STEP I: Patients must have measurable or evaluable disease as defined by having one or
more of the following, obtained within 28 days prior to randomization:
- >= 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis
- >= 200 mg/24 hours (hrs) of monoclonal protein on a 24 hour urine protein
electrophoresis
- Involved free light chain >= 10 mg/dL or >= 100 mg/L AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)
- Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
- Serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and
serum free light chain (FLC) assay are required to be performed within 28 days
prior to randomization; a bone marrow biopsy and/or aspirate is required within
28 days if bone marrow is being followed for response
- NOTE: UPEP (on a 24-hour collection) is required, no substitute method is
acceptable; urine must be followed monthly if the baseline urine M-spike is
>= 200 mg/24 hr; please note that if both serum and urine M-components are
present, both must be followed in order to evaluate response
- NOTE: The serum free light chain test is required to be done if the patient
does not have measurable disease in the serum or urine; measurable disease
in the serum is defined as having a serum M-spike >= 1 g/dL; measurable
disease in the urine is defined as having a urine M-spike >= 200 mg/24 hr
- STEP I: Hemoglobin >= 8 g/dL (obtained within 28 days prior to randomization)
- STEP I: Untransfused platelet count >= 75,000 cells/mm^3 (obtained within 28 days
prior to randomization)
- STEP I: Absolute neutrophil count >= 1000 cells/mm^3 (obtained within 28 days prior to
randomization)
- STEP I: Calculated creatinine clearance >= 30 mL/min (obtained within 28 days prior to
randomization)
- STEP I: Bilirubin =< 1.5 mg/dL (obtained within 28 days prior to randomization)
- STEP I: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT])
and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])
< 2.5 times the upper limit of normal (obtained within 28 days prior to randomization)
- STEP I: Patients must have received no more than one cycle (4 weeks or less) of prior
chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of
prednisone) for treatment of symptomatic myeloma; they should not have been exposed to
lenalidomide, bortezomib or carfilzomib for treatment of symptomatic myeloma; prior
radiation therapy to symptomatic lesions is allowed provided there are no residual
toxicity related to radiation and blood counts that meet the study requirements
- STEP I: Prior systemic glucocorticoid use for the treatment of non-malignant disorders
is permitted; prior or concurrent topical or localized glucocorticoid therapy to treat
non-malignant comorbid disorders is permitted
- STEP I: Patients must not have active, uncontrolled seizure disorder; patients must
have had no seizures in the last 6 months
- STEP I: Patients must not have uncontrolled intercurrent illness including
uncontrolled hypertension, symptomatic congestive heart failure, unstable angina,
uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation
that would limit compliance with the study, or a prior history of Stevens Johnson
syndrome
- STEP I: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
(performance status [PS] 3 allowed if secondary to pain)
- STEP I: Patients with monoclonal gammopathy of undetermined significance or
asymptomatic multiple myeloma are not eligible
- STEP I: Patients must not have grade 2 or higher peripheral neuropathy by Common
Terminology Criteria for Adverse Events (CTCAE) 4.0
- STEP I: Patients must not have active, uncontrolled infection
- STEP I: Patients may have a history of current or previous deep vein thrombosis or
pulmonary embolism but must be willing to take some form of anti-coagulation as
prophylaxis if they are not currently on full-dose anticoagulation
- STEP I: Patients should not have New York Heart Association classification III or IV
heart failure or myocardial infarction within the previous 6 months
- STEP I: Patients with a history of prior malignancy are eligible provided they were
treated with curative intent and do not require active therapy (currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma ?in situ? of the cervix
or breast are not excluded)
- STEP I: 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 starting lenalidomide 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 throughout the entire
duration of study treatment, and for 28 days after the last dose of lenalidomide; FCBP
must also agree to ongoing pregnancy testing; all patients must be counseled at a
minimum of every 28 days about pregnancy precautions and risks of fetal exposure;
female subjects must agree to use contraception or abstinence for 30 days after last
dose of carfilzomib
- A female of childbearing potential is any woman, regardless of sexual orientation
or whether they have undergone tubal ligation, who meets the following criteria:
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
- STEP I: Sexually active males must be willing to use a condom (even if they have
undergone a prior vasectomy) while having intercourse, while taking lenalidomide and
for 28 days after stopping lenalidomide; male subjects must also agree to abstain from
donating blood, semen, or sperm during study participation and for at least 28 days
after discontinuation from lenalidomide; male subjects must be willing to use condoms
for 90 days after discontinuation of carfilzomib
- STEP I: The following patients will be excluded:
- Pregnant women
- Nursing women
- STEP I: Human immunodeficiency virus (HIV) infection is not excluded; known HIV
positive patients must meet the following criteria:
- Cluster of differentiation (CD)4 cell count >= 350/mm^3
- No history of acquired immune deficiency syndrome (AIDS)-related illness
- Not currently prescribed zidovudine or stavudine
- STEP I: Patient enrolling to this study must agree to register to the mandatory
RevAssist program, and be willing and able to comply with the requirements of
RevAssist
- STEP II: Patients must have complete induction without experiencing progression or
patients must have received at least 6 cycles on Arm A and 4 cycles on Arm B but
stopped induction therapy due to adverse events
- STEP II: Step 2 registration must be within 6 weeks of completing step 1 therapy
- STEP II: Patients must not have received any non-protocol therapy outside of the
assigned induction therapy including stem cell transplant
- STEP II: ECOG performance status 0, 1, or 2 (PS 3 allowed if secondary to pain)
- STEP II: Any adverse event related to step 1 therapy must have resolved to grade 2 or
less
- STEP II: Hemoglobin >= 8 g/dL (within 28 days prior to randomization to Step II)
- STEP II: Platelet count >= 75,000 cells/mm^3 (within 28 days prior to randomization to
Step II)
- STEP II: Absolute neutrophil count >= 1000 cells/mm^3 (within 28 days prior to
randomization to Step II)
- STEP II: Calculated creatinine clearance >= 30 mL/min (within 28 days prior to
randomization to Step II)
- STEP II: Bilirubin =< 1.5 mg/dL (within 28 days prior to randomization to Step II)
- STEP II: SGPT (ALT) and SGOT (AST) < 2.5 times the upper limit of normal (within 28
days prior to randomization to Step II)
- STEP II: 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 starting lenalidomide 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 throughout the entire
duration of study treatment, and for 28 days after the last dose of lenalidomide; FCBP
must also agree to ongoing pregnancy testing; all patients must be counseled at a
minimum of every 28 days about pregnancy precautions and risks of fetal exposure
- A female of childbearing potential is any woman, regardless of sexual orientation
or whether they have undergone tubal ligation, who meets the following criteria:
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
- STEP II: Sexually active males must be willing to use a condom (even if they have
undergone a prior vasectomy) while having intercourse, while taking lenalidomide and
for 28 days after stopping lenalidomide; male subjects must also agree to abstain from
donating blood, semen, or sperm during study participation and for at least 28 days
after discontinuation from lenalidomide; males must agree to use contraception and
agree to not donate sperm for at least 90 days after the last day of carfilzomib
- STEP II: The following patients will be excluded:
- Pregnant women
- Nursing women
- STEP II: Patient enrolling to this study must agree to register to the mandatory
RevAssist program and be willing and able to comply with the requirements of RevAssist