Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma (CLARION)

Amgen

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Carfilzomib; Drug: Bortezomib; Drug: Melphalan; Drug: Prednisone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01818752

2012-005283-97 (EudraCT Number)

2012-005

20130397 (Other Identifier)

Details and patient eligibility

About

The primary objective was to compare the progression-free survival of transplant ineligible patients newly diagnosed with multiple myeloma who were treated with carfilzomib, melphalan and prednisone (CMP) or with Velcade® (bortezomib), melphalan and prednisone (VMP).

Enrollment: 955 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Newly diagnosed symptomatic multiple myeloma (per International Myeloma Working Group [IMWG] diagnostic criteria)

2. Transplant ineligibility

3. Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to randomization):

   • Serum M-protein ≥ 0.5 g/dL, or
   • Urine M-protein ≥ 200 mg/24 hours, or
   • In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ratio (SFLC kappa lambda ratio < 0.26 or > 1.65)

4. No prior treatment for multiple myeloma

5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion criteria

1. Multiple myeloma of IgM (immunoglobulin M) subtype
2. Glucocorticoid therapy within 14 days prior to randomization that equals or exceeds a cumulative dose of 160 mg of dexamethasone
3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
4. Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
5. Waldenström macroglobulinemia (WM)
6. Known amyloidosis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

955 participants in 2 patient groups

Carfilzomib, Melphalan, Prednisone

Experimental group

Description:

Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Treatment:

Drug: Melphalan

Drug: Carfilzomib

Drug: Prednisone

Bortezomib, Melphalan, Prednisone

Active Comparator group

Description:

Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Treatment:

Drug: Bortezomib

Drug: Melphalan

Drug: Prednisone