Phase 1b Study of Weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma

Amgen

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Lenalidomide; Drug: Dexamethasone; Drug: Carfilzomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02335983

CFZ013

Details and patient eligibility

About

The purpose of the study is to assess the safety, tolerability and activity of a once-weekly regimen of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma.

Enrollment: 107 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Newly diagnosed or relapsed multiple myeloma
2. Measureable disease by serum M protein, or urine M protein, or serum free light chain (SFLC) and an abnormal serum kappa lambda ratio (for subjects without detectable serum or urine M-protein), or serum quantitative immunoglobulin A (glgA) (for immunoglobulin (Ig) A subjects whose disease can only be reliable measured by qlgA).
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2
4. Left ventricular ejection fraction (LVEF) ≥ 40%

Key Exclusion Criteria:

1. Waldenström macroglobulinemia

2. For newly diagnosed multiple myeloma: multiple myeloma of IgM subtype

3. For relapsed disease:

   1. If treated with a lenalidomide and dexamethasone combination, progression during the first 3 months after initiating treatment.
   2. Any progression during treatment if the lenalidomide and dexamethasone regimen was the most recent line of therapy.
   3. Any prior treatment with carfilzomib

4. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

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

6. Myelodysplastic syndrome

7. Amyloidosis

8. Prior treatment with carfilzomib or oprozomib

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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107 participants in 6 patient groups

RRMM Dose-evaluation: Carfilzomib 56 mg/m²

Experimental group

Description:

Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Lenalidomide

RRMM Dose-evaluation: Carfilzomib 70 mg/m²

Experimental group

Description:

Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Lenalidomide

RRMM Dose-expansion: Carfilzomib 70 mg/m²

Experimental group

Description:

Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Lenalidomide

NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²

Experimental group

Description:

Participants with newly diagnosed multiple myeloma (NDMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1 day 1, 56 mg/m² on cycle 1 days 8 and 15, and then 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Lenalidomide

NDMM Dose-expansion: Carfilzomib 70 mg/m²

Experimental group

Description:

Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Lenalidomide

NDMM Dose-expansion: Carfilzomib 56 mg/m²

Experimental group

Description:

Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.

Treatment:

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Lenalidomide