Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR)

Amgen

Status and phase: Completed; Phase 3

Conditions: Refractory Multiple Myeloma; Relapsed Multiple Myeloma

Treatments: Drug: Carfilzomib; Drug: Daratumumab; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT03158688

20160275

2016-003554-33 (EudraCT Number)

Details and patient eligibility

About

Compare carfizomib, dexamethasone, and daratumumab (KdD) to Carfilzomib and dexamethasone (Kd) in terms of progression free survival (PFS) in participants with multiple myeloma who have relapsed after 1 to 3 prior therapies.

Full description

This is a phase 3 multicenter, open-label, randomized study in participants with relapsed or refractory multiple myeloma (RRMM) who have received 1 to 3 prior therapies.

Participants receive the treatment determined by randomization for a maximum of approximately 5 years, up to 30 days prior to the final analysis data cutoff (DCO) date or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or death (whichever occurs first). No crossover between the treatment arms is allowed.

This was an open-label study. However, the assessment of response and disease progression for the primary analysis was determined by an Independent Review Committee (IRC) in a blinded manner. Sensitivity analyses of response and disease progression were determined centrally by the sponsor using a validated computer algorithm (Onyx Response Computational Assessment [ORCA]) in a blinded manner.

Following progression or discontinuation of study drug(s), participants will have 1 follow-up visit (30 days [+3} after last dose of all study drug[s]). After disease progression, data on survival status and subsequent antimyeloma therapy will be gathered at long-term follow-up (LTFU) visits every 12 weeks (+/-2 weeks) until the Final Analysis DCO.

Enrollment: 466 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Criteria 1 Relapsed or progressive multiple myeloma after last treatment
• Criteria 2 Males or females ≥ 18 years of age
• Criteria 3 Measurable disease with at least 1 of the following assessed within 21 days prior to randomization:
• IgG multiple myeloma: serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL,
• IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL,
• urine M-protein ≥ 200 mg/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
• Criteria 4 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
• Criteria 5 Prior therapy with carfilzomib is allowed as long as the patient had at least a partial response (PR) to most recent therapy with carfilzomib, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and will have at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not proteasome inhibitors or CD38 antibodies during this 6-month carfilzomib treatment free interval)
• Criteria 6 Prior therapy with anti-CD38 antibodies is allowed as long as the patient had at least a PR to most recent therapy with CD38 antibody, was not removed due to toxicity, did not relapse within 60 days from intensive treatment (at least every other week) of CD38 antibody therapy, and will have at least a 6 month CD38 antibody treatment-free interval from last dose received until first study treatment
• Other inclusion criteria may apply

Exclusion criteria

• Criteria 1 Waldenström macroglobulinemia
• Criteria 2 Multiple myeloma of IgM subtype
• Criteria 3 POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Criteria 4 Plasma cell leukemia (> 2.0 * 10^9/L circulating plasma cells by standard differential)
• Criteria 5 Myelodysplastic syndrome
• Criteria 6 Known moderate or severe persistent asthma within the past 2 years
• Criteria 7 Known chronic obstructive pulmonary disease (COPD) with a FEV1 < 50% of predicted normal
• Criteria 8 Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization
• Other exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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466 participants in 2 patient groups

Kd - Carfilzomib and Dexamethasone

Active Comparator group

Description:

Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles.

Treatment:

Drug: Dexamethasone

Drug: Carfilzomib

KdD - Carfilzomib, Dexamethasone and Daratumumab

Experimental group

Description:

Carfilzomib was administered intravenously (IV) at 20 mg/m\^2 in Cycle 1: days 1 and 2; at 56 mg/m\^2 in Cycle 1: days 8, 9, 15 and 16. The 56 mg/m\^2 dosage was continued in Cycles 2+ on days 1, 2, 8, 9, 15 and 16. Dexamethasone was taken by IV infusion at 20 mg on Cycle 1, days 1 and 2 (in Cycles 2+, days 1 and 2 could be either oral or IV) and either orally or by IV infusion on days 8, 9, 15 and 16 and at 40 mg on day 22 of all 28-day cycles. The administration of dexamethasone was given on carfilzomib and/or daratumumab IV infusion days. Daratumumab was administered by IV at 8 mg/kg on Cycle 1: days 1 and 2; at 16 mg/kg on Cycle 1: days 8, 15 and 22, and Cycle 2: days 1, 8, 15, and 22. The 16 mg/kg dosage was continued on Cycles 3-6: days 1 and 15. The 16 mg/kg was further continued on Cycles 7+: day 1 only.

Treatment:

Drug: Dexamethasone

Drug: Daratumumab

Drug: Carfilzomib