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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 : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

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.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Multiple Myeloma Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 460 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : May 8, 2019
Estimated Primary Completion Date : December 10, 2021
Estimated Study Completion Date : December 10, 2021


Arm Intervention/treatment
Active Comparator: Carfilzomib once-weekly
Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using once-weekly carfilzomib 56 mg/m2
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: 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

Active Comparator: Carfilzomib twice-weekly
Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using twice-weekly carfilzomib 27 mg/m2
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




Primary Outcome Measures :
  1. 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]


Secondary Outcome Measures :
  1. 1-year Progression free survival [ Time Frame: 1 year ]
  2. Convenience [ Time Frame: Through study completion, an average of 14 months ]
    As measured by the Patient-reported convenience with carfilzomib dosing schedule question

  3. Subject incidence of treatment-emergent adverse events [ Time Frame: Through study completion, an average of 14 months ]
  4. Additional efficacy parameter - Time to Response [ Time Frame: Through study completion, an average of 14 months ]
    As measured by Time to Response (TTR)

  5. Additional efficacy parameter - Duration of Response [ Time Frame: Through study completion, an average of 14 months ]
    Duration of Response (DOR)

  6. Additional efficacy parameter - Time to Progression [ Time Frame: Through study completion, an average of 14 months ]
    Time to Progression (TTP)

  7. 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

  8. 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

  9. 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

  10. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 lenalidomide and dexamethasone is allowed, as long as the patient had at least a PR to most recent therapy with PI or lenalidomide and dexamethasone, was not removed due to toxicity, and will have at least a 6-month PI or lenalidomide and dexamethasone treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with lenalidomide during this 6-month PI or lenalidomide and dexamethasone treatment-free interval).

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 (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


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): NCT03859427


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03859427     History of Changes
Other Study ID Numbers: 20180015
First Posted: March 1, 2019    Key Record Dates
Last Update Posted: October 22, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Bone Marrow Cancer
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