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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 : Recruiting
First Posted : January 20, 2016
Last Update Posted : March 13, 2018
Sponsor:
Information provided by (Responsible Party):
University of Chicago

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Lenalidomide Drug: Carfilzomib Drug: Dexamethasone Drug: Lenalidomide (Control) Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 3 Randomized Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma
Actual Study Start Date : April 26, 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : May 2020


Arm Intervention/treatment
Active Comparator: Lenalidomide (Control)
Treatment with lenalidomide only
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

Experimental: Experimental Combination Regimen
Experimental arm using a combination of Carfilzomib, Lenalidomide and Dexamethasone
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02659293


Contacts
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Contact: Jennifer Nam 773-702-7716 jnam@medicine.bsd.uchicago.edu

Locations
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United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Jennifer Nam    773-702-7716    jnam@medicine.bsd.uchicago.edu   
Principal Investigator: Andrzej Jakubowiak, M.D.         
United States, Michigan
Wayne State University - Karmanos Cacner Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Abhinav Deol, MD    313-576-8093      
Poland
Polish Myeloma Consortium Recruiting
Poznań, Poland
Contact: Dominik Dytfeld, dr n. med.       dytfeld@me.com   
Sponsors and Collaborators
University of Chicago
Investigators
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Principal Investigator: Andrzej Jakubowiak, MD, PhD University of Chicago

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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02659293     History of Changes
Other Study ID Numbers: IRB15-1286
First Posted: January 20, 2016    Key Record Dates
Last Update Posted: March 13, 2018
Last Verified: March 2018

Keywords provided by University of Chicago:
Multiple myeloma
stem-cell transplant
Symptomatic myeloma
lenalidomide
carfilzomib
dexamethasone

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Lenalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors