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Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT02659293
Recruitment Status : Active, not recruiting
First Posted : January 20, 2016
Last Update Posted : June 30, 2021
Sponsor:
Information provided by (Responsible Party):
University of Chicago

Tracking Information
First Submitted Date  ICMJE January 15, 2016
First Posted Date  ICMJE January 20, 2016
Last Update Posted Date June 30, 2021
Actual Study Start Date  ICMJE April 26, 2016
Estimated Primary Completion Date November 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
Progression free survival rates in participants receiving drug combination [ Time Frame: 4 years ]
Measurement of time to disease worsening as measured by International Myeloma Working Group (IMWG) response criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: January 19, 2016)
Time to progression or death [ Time Frame: From date of first treatment until maximum 6 year post randomization ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • Rate of minimal residual negative disease (MRD) in participants receiving drug combination [ Time Frame: 3 years ]
    Calculation of number of participants with MRD-negative disease.
  • Response rate in participants receiving drug combination [ Time Frame: 3 years ]
    Number of participants with disease response (e.g. improvement) as measured by International Myeloma Working Group (IMWG) response criteria.
  • Treatment-related side effects [ Time Frame: From date of screening until end of treatment ]
    Number of participants with grade 2 or greater treatment-related side effects as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Original Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2016)
  • Rate of minimal residual negatibe disease (MRD) calculated using chi-square or Fisher's tests [ Time Frame: From date of screening up until 36 months on treatment ]
  • Efficacy Rate of KRd arm versus lenalidomide arm [ Time Frame: From date of screening up until 36 months on treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma
Official Title  ICMJE Phase 3 Randomized Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma
Brief Summary This is a Phase 3 randomized trial of carfilzomib, lenalidomide, dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma, eligible to subjects who completed autologous stem cell transplant for symptomatic myeloma who are considered for lenalidomide maintenance.
Detailed Description

Primary Objective:

  • To compare progression free survival between Kyprolis (Carfilzomib), Revlimid (lenalidomide), Dexamethasone (KRd) arm and lenalidomide arm

Secondary Objectives

  • To determine the rate of minimal residual negative disease (MRD) at 6 and 12 months after randomization
  • To compare the efficacy (rate of partial response, very good partial response, complete response, and stringent complete response) of KRd vs. Lenalidomide alone after randomization
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Lenalidomide
    • Cycle 1: 15 mg days 1-21
    • Cycles 2-4: 25 mg days 1-21 if tolerated, otherwise continue at lower dose
    • Cycles 5 and beyond: best tolerated dose days 1-21
    Other Name: Revlimid
  • Drug: Carfilzomib
    • Cycle 1: 20 mg/m2 Days 1, 2; 36 mg/m2 Days 8, 9, 15, 16. Alternatively, intermediate dose escalation (to 27mg/m2 on days 8,9 of cycle 1) will be al12,lowed at the treating physician's discretion.
    • Cycle 2-4: 36 mg/m2 if tolerated Days 1, 2, 8, 9, 15, 16
    • Cycles 5-8 (patients that are MRD- and have no risk factors at the end of cycle 6) and Cycle 5 - 36 (for MRD+ patients and high risk patients at the end of cycle 6): best tolerated dose Days 1, 2, 15, 16
    Other Name: Kyprolis
  • Drug: Dexamethasone
    • Cycles 1 - 4: 20 mg PO or IV per dose Days 1, 8, 15, 22
    • Cycles 5+: 20 mg or best tolerated dose PO or IV per dose Days 1, 8, 15, 22
  • Drug: Lenalidomide (Control)
    • Cycles 1-4: Days 1-28. Lenalidomide will begin at a dose of 10 mg PO daily (2 capsules per day). After three months, the dose will be increased, provided ANC ≥ 1,000/µL, platelet count ≥ 75,000/µL, and all nonhematologic toxicity is ≤ grade 1, to 15 mg PO daily (3 capsules per day).
    • Cycles 5 and beyond: best tolerated dose days 1-28
    Other Name: Revlimid
Study Arms  ICMJE
  • Active Comparator: Lenalidomide (Control)
    Treatment with lenalidomide only
    Intervention: Drug: Lenalidomide (Control)
  • Experimental: Experimental Combination Regimen
    Experimental arm using a combination of Carfilzomib, Lenalidomide and Dexamethasone
    Interventions:
    • Drug: Lenalidomide
    • Drug: Carfilzomib
    • Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 19, 2016)
180
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2026
Estimated Primary Completion Date November 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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 in the first 100 days after stem cell transplantation.
  2. Patients must be within 12 months of initiation of induction therapy and must have had not more than 2 prior induction regimens.
  3. Bone marrow specimen will be required at study entry; available DNA sample will be used for calibration step for MRD evaluation by gene sequencing.
  4. Males and females ≥ 18 years of age
  5. ECOG performance status of 0-1
  6. Adequate hepatic function, with bilirubin ≤ 1.5 x ULN and aspirate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN
  7. ANC ≥ 1.0 x 109/L, hemoglobin ≥ 8 g/dL, platelet count ≥ 75 x 109/L.
  8. Calculated creatinine clearance (by Cockcroft-Gault) ≥ 50 ml/min or serum creatinine below 2 mg/dL
  9. 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).
  10. 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.

    UCM IRB CRd vs. R Version 1.0 Page 11

  11. 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.
  12. All study participants in the US must be consented to and registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of Revlimid REMS®.
  13. Voluntary written informed consent

Exclusion Criteria:

  1. Patients who have had more than 12 months of prior therapy. Patients outside of this window may be considered for inclusion on a case-by-case basis.
  2. Patients who progressed after initial therapy.

    1. Subjects whose therapy changed due to suboptimal response, intolerance, etc., remain eligible, provided they do not meet criteria for progression.
    2. No more than two regimens for induction will be allowed excluding dexamethasone alone.
  3. Evidence of progressive disease as per International Myeloma Working Group (IMWG) criteria
  4. Patients who have already started or received post-transplant maintenance or consolidation regimen
  5. Patients not able to tolerate lenalidomide or carfilzomib or dexamethasone
  6. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  7. Plasma cell leukemia
  8. Waldenström's macroglobulinemia or IgM myeloma
  9. Peripheral neuropathy ≥ Grade 2 at screening
  10. Diarrhea > Grade 1 in the absence of antidiarrheals
  11. CNS involvement
  12. Pregnant or lactating females
  13. Radiotherapy within 14 days before randomization. Seven days may be considered if to single area.
  14. Major surgery within 3 weeks prior to first dose
  15. Myocardial infarction within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  16. Prior or concurrent deep vein thrombosis or pulmonary embolism
  17. Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening
  18. Uncontrolled hypertension or diabetes
  19. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
  20. 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.
  21. Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) 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
  22. Any clinically significant medical disease or condition that, in the Treating Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Poland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02659293
Other Study ID Numbers  ICMJE IRB15-1286
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University of Chicago
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Chicago
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrzej Jakubowiak, MD, PhD University of Chicago
PRS Account University of Chicago
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP