Lenalidomide with or without Carfilzomib and Dexamethasone in Treating Patients with Multiple Myeloma after Stem-Cell Transplant
This randomized phase III trial studies how well lenalidomide with or without carfilzomib and dexamethasone works in treating patients with multiple myeloma after stem-cell transplant. Lenalidomide may help the immune system kill abnormal blood cells or cancer cells. It may also prevent the growth of new blood vessels that tumors need to grow. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone is a drug used to reduce inflammation and lower the body’s immune response. Giving lenalidomide together with carfilzomib and dexamethasone may be an effective treatment for multiple myeloma.
Inclusion Criteria
- Patients who completed single autologous stem cell transplant after completion of at most 2 induction regimens (excluding dexamethasone alone) and are in at least stable disease compared to pre-induction in the first 100 days after stem cell transplantation
- Patients must be within 12 months of initiation of induction therapy and must have had not more than 2 prior induction regimens
- Bone marrow specimen will be required at study entry; available deoxyribonucleic acid (DNA) sample from pre-induction bone marrow (BM) will be used for calibration step for MRD evaluation by gene sequencing
- Males and females ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
- Hemoglobin >= 8 g/dL
- Platelet count >= 75 x 10^9/L
- Calculated creatinine clearance (by Cockroft-Gault) >= 50 mL/min or serum creatinine below 2 g/dL
- Females of childbearing potential (FCBP) must have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL) prior to initiating lenalidomide: the first pregnancy test must be performed within 10-14 days before and the second pregnancy test must be performed within 24 hours before lenalidomide is prescribed for cycle 1 (prescriptions must be filled within 7 days)
- FCBP must agree to use 2 reliable 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 lenalidomide; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study
- Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy
- All study participants in the United States (US) must be consented to and registered into the mandatory Revlimid (lenalidomide) REMS (registered trademark) program and be willing and able to comply with the requirements of Revlimid REMS
- Voluntary written informed consent
Exclusion Criteria
- Patients who have had more than 12 months of prior therapy; patients outside of this window may be considered for inclusion; please contact the sponsor’s representative in Poland or the lead primary investigator as appropriate on a case-by-case basis
- Patients who progressed after initial therapy * Subjects whose therapy changed due to suboptimal response, intolerance, etc., remain eligible, provided they do not meet criteria for progression * No more than two regimens will be allowed excluding dexamethasone alone
- Potential subjects with evidence of progressive disease as per International Myeloma Working Group (IMWG) criteria
- Patients who have already started or received post-transplant maintenance or consolidation regimen
- Patients not able to tolerate lenalidomide or carfilzomib or dexamethasone
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia
- Waldenstrom’s macroglobulinemia or immunoglobulin (Ig)M myeloma
- Peripheral neuropathy >= grade 2 at screening
- Diarrhea > grade 1 in the absence of antidiarrheals
- Central nervous system (CNS) involvement
- Pregnant or lactating females
- Radiotherapy within 14 days before randomization; seven days may be considered if to single area
- Major surgery within 3 weeks prior to first dose
- Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- Prior or concurrent pulmonary embolism
- Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead electrocardiography (ECG) during screening
- Uncontrolled hypertension or diabetes
- Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
- Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are seropositive because of hepatitis B virus vaccine are eligible
- Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone
- Any clinically significant medical disease or condition that, in the investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent
Additional locations may be listed on ClinicalTrials.gov for NCT02659293.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To compare progression free survival (PFS) between carfilzomib, lenalidomide, dexamethasone (KRd) and lenalidomide arm after randomization.
SECONDARY OBJECTIVES:
I. To determine the rate of minimal residual disease (MRD)-negative disease at 6, 12, 18, 24, and 36 months after randomization.
II. To compare the efficacy (rate of partial response [PR], very good partial response [VGPR], complete response [CR], and stringent complete response [sCR]) of KRd versus (vs.) lenalidomide alone after randomization.
III. To evaluate the safety and tolerability of KRd compared to lenalidomide alone.
EXPLORATORY OBJECTIVE:
I. Determination of markers of response based on pre-treatment characteristics.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive lenalidomide orally (PO) on days 1-21, carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16 of cycles 1-4 and then days 1, 2, 15, and 16 of each subsequent cycle and dexamethasone PO or IV on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients completing 8 cycles (who are MRD-negative [Neg] and have no risk factors, checked at the end of cycle 6) or 36 cycles continue to receive lenalidomide alone in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 3 years and yearly for up to 6 years from randomization.
Trial PhasePhase III
Trial Typetreatment
Lead OrganizationUniversity of Chicago Comprehensive Cancer Center
Principal InvestigatorAndrzej J. Jakubowiak
- Primary IDIRB15-1286
- Secondary IDsNCI-2016-00079
- ClinicalTrials.gov IDNCT02659293