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A Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (ARROW2)

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ClinicalTrials.gov Identifier: NCT03859427
Recruitment Status : Recruiting
First Posted : March 1, 2019
Last Update Posted : November 15, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE January 14, 2019
First Posted Date  ICMJE March 1, 2019
Last Update Posted Date November 15, 2019
Actual Study Start Date  ICMJE May 8, 2019
Estimated Primary Completion Date December 10, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2019)
Overall Response Rate (ORR) [ Time Frame: Through study completion, an average of 14 months ]
ORR defined as the proportion of best overall response of stringent complete response [sCR], complete response [CR], very good partial response [VGPR] and partial response [PR] per International Myeloma Working Group Uniform Response Criteria [IMWG-URC]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03859427 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2019)
  • 1-year Progression free survival [ Time Frame: 1 year ]
  • Convenience [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Patient-reported convenience with carfilzomib dosing schedule question
  • Subject incidence of treatment-emergent adverse events [ Time Frame: Through study completion, an average of 14 months ]
  • Additional efficacy parameter - Time to Response [ Time Frame: Through study completion, an average of 14 months ]
    As measured by Time to Response (TTR)
  • Additional efficacy parameter - Duration of Response [ Time Frame: Through study completion, an average of 14 months ]
    Duration of Response (DOR)
  • Additional efficacy parameter - Time to Progression [ Time Frame: Through study completion, an average of 14 months ]
    Time to Progression (TTP)
  • 1-year Overall Survival [ Time Frame: 1 year ]
  • MRD[-]CR rate [ Time Frame: Through study completion, an average of 14 months ]
    Defined as achievement of CR or better by Independent Review Committee (IRC) per IMWG-URC and achievement of Minimal Residual Disease (MRD) negativity as assessed by next-generation sequencing method at a 10^ -5 threshold
  • MRD[-] rate at 12 months [ Time Frame: 12 months ]
    Defined as achievement of Minimal Residual Disease (MRD) negativity at 12 months (+/- 2 weeks) from randomisation as assessed by next-generation sequencing method at a 10^ -5 threshold
  • Physical functioning and role functioning [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Physical Functioning and Role Functioning scales of the European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30), a 30-item generic instrument for use in cancer subjects across tumor types
  • Treatment satisfaction as measured by the Satisfaction with Therapy (SWT) subscale of the Cancer Therapy Satisfaction Questionnaire (CTSQ) [ Time Frame: 4 months ]
    Cancer Therapy Satisfaction Questionnaire (CTSQ) - measures treatment satisfaction in individuals with cancer
Original Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2019)
  • 1-year Progression free survival [ Time Frame: 1 year ]
  • Convenience [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Patient-reported convenience with carfilzomib dosing schedule question
  • Subject incidence of treatment-emergent adverse events [ Time Frame: Through study completion, an average of 14 months ]
  • Additional efficacy parameter - Time to Response [ Time Frame: Through study completion, an average of 14 months ]
    As measured by Time to Response (TTR)
  • Additional efficacy parameter - Duration of Response [ Time Frame: Through study completion, an average of 14 months ]
    Duration of Response (DOR)
  • Additional efficacy parameter - Time to Progression [ Time Frame: Through study completion, an average of 14 months ]
    Time to Progression (TTP)
  • MRD[-]CR rate [ Time Frame: Through study completion, an average of 14 months ]
    Defined as achievement of CR or better by Independent Review Committee (IRC) per IMWG-URC and achievement of Minimal Residual Disease (MRD) negativity as assessed by next-generation sequencing method at a 10^ -5 threshold
  • MRD[-] rate at 12 months [ Time Frame: 12 months ]
    Defined as achievement of Minimal Residual Disease (MRD) negativity at 12 months (+/- 2 weeks) from randomisation as assessed by next-generation sequencing method at a 10^ -5 threshold
  • Physical functioning and role functioning [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Physical Functioning and Role Functioning scales of the European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30), a 30-item generic instrument for use in cancer subjects across tumor types
  • Treatment satisfaction as measured by the Satisfaction with Therapy (SWT) subscale of the Cancer Therapy Satisfaction Questionnaire (CTSQ) [ Time Frame: 4 months ]
    Cancer Therapy Satisfaction Questionnaire (CTSQ) - measures treatment satisfaction in individuals with cancer
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: February 27, 2019)
  • Health Related Quality of Life over time as measured by the functional, disease symptom, side effect, body image, and future perspectives scales of the EORTC QLQ-C30 [ Time Frame: Through study completion, an average of 14 months ]
    European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30), a 30-item generic instrument for use in cancer subjects across tumor types
  • Health Related Quality of Life over time as measured by the functional, disease symptom, side effect, body image, and future perspectives scales of the EORTC QLQ-MY20 [ Time Frame: Through study completion, an average of 14 months ]
    European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Multiple Myeloma Module, (EORTC QLQ-MY20) a 20 item instrument to assess quality of life in patients with multiple myeloma
  • Healthcare resource utilization associated with treatment-related AEs as measured by duration of hospitalizations [ Time Frame: Through study completion, an average of 14 months ]
    Details on medical care encounters as measured by duration of hospitalizations associated with treatment-related adverse events
  • Healthcare resource utilization associated with treatment-related AEs as measured by number of diagnostic procedures [ Time Frame: Through study completion, an average of 14 months ]
    Details on inpatient, outpatient and follow up care as measured by number of diagnostic procedures associated with treatment-related adverse events
  • Healthcare resource utilization associated with treatment-related AEs as measured by type of diagnostic procedures [ Time Frame: Through study completion, an average of 14 months ]
    Details on inpatient, outpatient and follow up care as measured by type of diagnostic procedures associated with treatment-related adverse events
  • Healthcare resource utilization associated with treatment-related AEs as measured by number of therapeutic procedures [ Time Frame: Through study completion, an average of 14 months ]
    Details on inpatient, outpatient and follow up care as measured by number of therapeutic procedures associated with treatment-related adverse events
  • Healthcare resource utilization associated with treatment-related AEs as measured by type of therapeutic procedures [ Time Frame: Through study completion, an average of 14 months ]
    Details on inpatient, outpatient and follow up care as measured by type of therapeutic procedures associated with treatment-related adverse events
  • Healthcare resource utilization associated with treatment-related AEs as measured by number of surgeries [ Time Frame: Through study completion, an average of 14 months ]
    Details on medical care encounters as measured by number of surgeries associated with treatment-related adverse events
  • Healthcare resource utilization associated with treatment-related AEs as measured by duration of surgeries [ Time Frame: Through study completion, an average of 14 months ]
    Details on medical care encounters as measured by duration of surgeries associated with treatment-related adverse events
  • Healthcare resource utilization associated with treatment-related AEs as measured by number of out patient visits [ Time Frame: Through study completion, an average of 14 months ]
    Details on medical care encounters as measured by number of out patient visits associated with treatment-related adverse events
  • Healthcare resource utilization associated with treatment-related AEs as measured by duration of out patient visits [ Time Frame: Through study completion, an average of 14 months ]
    Details on medical care encounters as measured by duration of out patient visits associated with treatment-related adverse events
  • Healthcare resource utilization associated with treatment-related AEs as measured by use of concomitant medications [ Time Frame: Through study completion, an average of 14 months ]
    Details on inpatient, outpatient and follow up care as measured by use of concomitant medications associated with treatment-related adverse events
  • Infusion related travel burden as measured by overall infusion center visit time [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Infusion-related Travel Burden Questionnaire: Overall infusion center visit time to receive carfilzomib infusion defined as the difference in arrival and departure time at infusion clinic
  • Infusion related travel burden as measured by distance travelled to infusion center [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Infusion-related Travel Burden Questionnaire: Distance travelled to infusion center one-way
  • Infusion related travel burden as measured by time taken to travel to infusion center [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Infusion-related Travel Burden Questionnaire: Time taken to travel to infusion center one-way
  • Patient reported health status as measured by the Index Score of the EQ-5D-5L [ Time Frame: Through study completion, an average of 14 months ]
    Health status over time as measured by the index score of the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L), an instrument to assess generic health outcomes
  • Patient reported health status as measured by the EQ VAS of the EQ-5D-5L [ Time Frame: Through study completion, an average of 14 months ]
    Health status over time as measured by the EQ Visual Analogue Scale (EQ-VAS) of the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L), an instrument to assess generic health outcomes
  • Pharmacokinetics (PK) - Peak Plasma Concentration [Cmax] [ Time Frame: Through study completion, an average of 14 months ]
  • Pharmacokinetics (PK) - Area under the plasma concentration versus time curve (AUC) [ Time Frame: Through study completion, an average of 14 months ]
  • Pharmacokinetics (PK) - Half life [t ½] [ Time Frame: Through study completion, an average of 14 months ]
  • Pharmacodynamics (PDn) - rate of inhibition of proteasome activity relative to baseline [ Time Frame: Through study completion, an average of 14 months ]
  • Patient reported convenience and satisfaction with the KRd regimen measured with Satisfaction and Experience Questionnaire - Multiple Myeloma module (SEQ-MM) [ Time Frame: Through study completion, an average of 14 months ]
    Satisfaction and Experience Questionnaire - Multiple Myeloma Module (SEQ-MM), a 13 item instrument to assess subjects' convenience and satisfaction with their treatment for multiple myeloma
  • Patient reported Expectations of Therapy (ET) [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Cancer Therapy Satisfaction Questionnaire (CTSQ) - Expectations of Therapy (ET) subscale
  • Patient reported Feelings about Side Effects (FSE) [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Cancer Therapy Satisfaction Questionnaire (CTSQ) - Feelings about Side Effects (FSE) subscale
  • Patient Reported perception of convenience with carfilzomib dosing schedules [ Time Frame: Through study completion, an average of 14 months ]
    As measured by Patient reported perception of convenience with carfilzomib dosing schedules question
  • Patient reported bother by side effects of treatment [ Time Frame: Through study completion, an average of 14 months ]
    Item 'I am bothered by side effects of treatment' measured by Functional Assessment of Cancer Therapy General (FACT-G)
 
Descriptive Information
Brief Title  ICMJE A Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Official Title  ICMJE A Randomized, Open-label, Phase 3 Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (A.R.R.O.W.2)
Brief Summary Compare efficacy of 56 mg/m2 carfilzomib administered once-weekly in combination with lenalidomide and dexamethasone (KRd 56 mg/m2) to 27 mg/m2 carfilzomib administered twice-weekly in combination with lenalidomide and dexamethasone (KRd 27 mg/m2) in subjects with relapsed or refractory multiple myeloma (RRMM) with 1 to 3 prior lines of therapy.
Detailed Description Not Provided
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 Relapsed or Refractory Multiple Myeloma
Intervention  ICMJE
  • Drug: Carfilzomib
    Once weekly IV over 30 minutes on day 1, 8 and 15 of each 28 day cycle. The dose will be 20 mg/m2 on cycle 1 day 1 and 56 mg/m2 beginning with cycle 1 day 8 and thereafter. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent.
  • Drug: Carfilzomib
    Twice weekly IV over 10 minutes on day 1, 2, 8, 9, 15 and 16 of each 28 day cycle. The dose will be 20 mg/m2 on cycle 1 days 1 and 2 and 27 mg/m2 beginning with cycle 1 day 8 and thereafter. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent.
  • Drug: Lenalidomide
    Once daily orally 25 mg days 1 to 21 of each cycle. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent
  • Drug: Dexamethasone
    Once daily orally or by IV 40 mg days 1, 8 and 15 of each cycle. Also day 22 of cycles 1 to 9. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent
Study Arms  ICMJE
  • Active Comparator: Carfilzomib once-weekly
    Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using once-weekly carfilzomib 56 mg/m2
    Interventions:
    • Drug: Carfilzomib
    • Drug: Lenalidomide
    • Drug: Dexamethasone
  • Active Comparator: Carfilzomib twice-weekly
    Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using twice-weekly carfilzomib 27 mg/m2
    Interventions:
    • Drug: Carfilzomib
    • Drug: Lenalidomide
    • 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 27, 2019)
460
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 10, 2021
Estimated Primary Completion Date December 10, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Documented relapse or progressive multiple myeloma on or after any treatment (subjects refractory to the most recent line of therapy are eligible, unless last treatment contained PI or lenalidomide and dexamethasone).

Subjects must have at least PR to at least 1 line of prior therapy.

Subjects must have received at least 1 but not more than 3 prior lines of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation maintenance therapy will be considered as 1 line of therapy).

Prior therapy with a PI or the combination of lenalidomide and dexamethasone are allowed, if, the patient had at least a PR to the most recent therapy with a PI or lenalidomide and dexamethasone, neither PI or lenalidomide and dexamethasone in combination were ceased due to toxicity, the patient has not received a PI and has not received lenalidomide and dexamethasone in combination in the 6 months prior to first study treatment. (Patients are permitted to have received single agent lenalidomide as maintenance therapy during the 6 months prior to first treatment)

Previous treatment with a lenalidomide and dexamethasone containing regimen is allowed, as long as the subject did not progress during the first 3 months after initiating lenalidomide and dexamethasone containing therapy.

Measurable disease with at least 1 of the following assessed within 21 days prior to randomization:

  • Inmunoglobulin G (IgG) multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
  • Inmunoglobulin A (IgA), Inmunoglobulin D (IgD), Inmunoglobulin E (IgE) multiple myeloma: serum M-protein level ≥ 0.5 g/dL
  • Urine M-protein ≥ 200 mg per 24 hours
  • In subjects without measurable serum or urine M-protein, serum-free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio

Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 ≤ 2

Other inclusion criteria may apply

Exclusion Criteria:

Waldenström macroglobulinemia.

Multiple myeloma of Inmunoglobulin M (IgM) subtype.

Plasma cell leukemia (> 2.0 × 10^9 /L circulating plasma cells by standard differential).

Uncontrolled hypertension, defined as an average systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg despite optimal treatment (blood pressure to be measured following European Society of Hypertension/European Society of Cardiology 2013 guidelines).

Active congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization.

Calculated or measured creatinine clearance < 1.0 mL/s (calculation must be based on the Cockcroft and Gault formula) within 21 days prior to randomization.

Other exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com
Listed Location Countries  ICMJE Bulgaria,   Czechia,   France,   Germany,   Greece,   Japan,   Netherlands,   Romania,   Russian Federation,   Spain,   Sweden,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03859427
Other Study ID Numbers  ICMJE 20180015
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date November 2019

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