Clinical Trials /

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

NCT02335983

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02335983

Trial Eligibility

Document

Title

  • Brief Title: Phase 1b Study of Weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma
  • Official Title: Phase 1b Study of Carfilzomib Administered Once Weekly in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CFZ013
  • NCT ID: NCT02335983

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibPR-171, PR171, Kyprolis® (carfilzomib) for InjectionNDMM Dose-evaluation: Carfilzomib 56/70 mg/m²
LenalidomideRevlimid®NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²
DexamethasoneNDMM Dose-evaluation: Carfilzomib 56/70 mg/m²

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
RRMM Dose-evaluation: Carfilzomib 56 mg/m²ExperimentalParticipants 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.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
RRMM Dose-evaluation: Carfilzomib 70 mg/m²ExperimentalParticipants 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.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
RRMM Dose-expansion: Carfilzomib 70 mg/m²ExperimentalParticipants 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.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²ExperimentalParticipants 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.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
NDMM Dose-expansion: Carfilzomib 70 mg/m²ExperimentalParticipants 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.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
NDMM Dose-expansion: Carfilzomib 56 mg/m²ExperimentalParticipants 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.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone

Eligibility 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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Adverse Events (AEs)
Time Frame:From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants.
Safety Issue:
Description:Safety and tolerability were evaluated according to the type, incidence, and severity of adverse events. An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: fatal life threatening requires in-patient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event The severity of each AE was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.

Secondary Outcome Measures

Measure:Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Time Frame:Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Safety Issue:
Description:
Measure:Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Time Frame:Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Safety Issue:
Description:
Measure:Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Time Frame:Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Safety Issue:
Description:Response was determined by the investigator based on the International Myeloma Working Group Uniform Response Criteria (IMWG URC). ORR was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Responses must have been confirmed in 2 consecutive assessments at any time prior to initiation of any new therapy. Disease assessments included serum protein electrophoresis (SPEP) with immunofixation, urine protein electrophoresis (UPEP; 24-hour assessment) with immunofixation, serum free light chain (SFLC), quantitative immunoglobulins, bone marrow aspirates to determine percent plasma cell involvement, and skeletal imaging for plasmacytoma evaluation.
Measure:Complete Response Rate (CRR)
Time Frame:Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Safety Issue:
Description:Complete Response Rate (CRR) is defined as the percentage of participants who achieved a best overall response of either stringent complete response (sCR) or complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM) CR: Negative serum and urine immunofixation, disappearance of any soft tissue plasmacytomas, < 5% plasma cells in BM, and normal SFLC ratio in participants with measurable disease only by SFLC.
Measure:Progression-free Survival (PFS)
Time Frame:From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Safety Issue:
Description:PFS is defined as the time from the first day of study treatment to the earlier of disease progression or death due to any cause. Disease progression was determined by the investigator according to IMWG-URC. Progressive Disease (PD): Increase of 25% from lowest value in serum M-component (absolute increase ≥ 0.5 g/dL), urine M-component (absolute increase ≥ 200 mg per 24 hours) and/or the difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL) in patients without measurable serum and urine M-protein levels, and/or any new or increase in size of bone lesions or soft tissue plasmacytomas, or development of hypercalcemia. PFS was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after > 1 consecutively missed assessment visit, were lost to follow-up or withdrew consent were censored at the date of last disease assessment.
Measure:Duration of Response (DOR)
Time Frame:From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Safety Issue:
Description:Duration of response (DOR) was calculated for participants who achieved a confirmed PR or better based on Investigator assessment and according to the IMWG URC. Duration of overall response is defined as the time from first documentation of response to disease progression or death due to any cause. DOR was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after > 1 consecutively missed disease assessment visit, were lost to follow-up, or withdrew consent were censored at the date of last disease assessment.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Amgen

Last Updated

November 6, 2020