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 |
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Recruitment Status :
Completed
First Posted : March 1, 2019
Last Update Posted : April 5, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsed or Refractory Multiple Myeloma | Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 454 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 |
| Actual Primary Completion Date : | March 31, 2023 |
| Actual Study Completion Date : | March 31, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Carfilzomib once-weekly
Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using once-weekly carfilzomib 56 mg/m2
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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 |
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Active Comparator: Carfilzomib twice-weekly
Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using twice-weekly carfilzomib 27 mg/m2
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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 |
- Overall Response (OR) [ Time Frame: Through study completion, an average of 14 months ]Defined as the 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]
- Progression free survival (PFS) [ Time Frame: Through study completion, an average of 14 months ]
- 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)
- Overall Survival [ Time Frame: Through study completion, an average of 14 months ]
- 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[-] status at 12 months [ Time Frame: 12 months ]Defined as achievement of Minimal Residual Disease (MRD) negativity at 12 months (+/- 4 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Multiple myeloma with documented relapse or progression after most recent myeloma treatment. Subjects refractory to the most recent line of therapy are eligible, unless last treatment contained proteasome inhibitor (PI) or lenalidomide and dexamethasone. Refractory is defined as disease that is nonresponsive or progresses within 60 days of last therapy.
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 treatment with a PI or lenalidomide and dexamethasone, neither PI or lenalidomide and dexamethasone containing treatment were ceased due to toxicity, the patient has not relapsed within 60 days of discontinuation of the PI or lenalidomide and dexamethasone containing treatment. A history of prior neuropathy is permitted if this was not grade 3, grade 4 or grade 2 with pain and if not resolved within the 14 days before enrollment, is less than or equal to grade 2 without pain. Patients are permitted to have received single agent lenalidomide as maintenance therapy within 60 days of enrollment.
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:
- Immunoglobulin G (IgG) multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
- Immunoglobulin A (IgA), Immunoglobulin D (IgD), Immunoglobulin 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 Immunoglobulin M (IgM) subtype.
Plasma cell leukemia (> 2.0 × 10^9 /L circulating plasma cells by standard differential).
Uncontrolled hypertension, defined as a subject whose blood pressure is greater than or equal to 160 mmHg systolic or greater than or equal to 100 mmHg diastolic when taken in accordance with the European Society of Hypertension/European Society of Cardiology 2018 guidelines (Section 12.10; Williams et al, 2018).
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 < 30 mL/min (calculation must be based on the Cockcroft and Gault formula) within 28 days prior to randomization.
Other exclusion criteria may apply
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
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| Study Director: | MD | Amgen |
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT03859427 |
| Other Study ID Numbers: |
20180015 |
| First Posted: | March 1, 2019 Key Record Dates |
| Last Update Posted: | April 5, 2023 |
| Last Verified: | April 2023 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Bone Marrow Cancer |
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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 |
Lenalidomide 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 Immunologic Factors Angiogenesis Inhibitors Angiogenesis Modulating Agents |