Clinical trial NCT04191616: Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet
Official title: An Open-label, Phase 2 Study Treating Subjects With First or Second Relapse of Multiple Myeloma With Carfilzomib, Pomalidomide, and Dexamethasone (KPd)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: Multiple Myeloma
RRMM
Open-label
First Relapse Multiple Myeloma
Second Relapse Multiple Myeloma
Refractory to Lenalidomide
Triplicate Treatment Regimen
Dexamethasone
Carfilzomib
Pomalidomide
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2019-12-10
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Study Evaluating Treatment of Multiple Myeloma with Carfilzomib in Combination with Pomalidomide and Dexamethasone

Detailed description: An Open-label, Phase 2 Study Treating Subjects with First or Second Relapse of Multiple Myeloma with Carfilzomib, Pomalidomide, and Dexamethasone (KPd)

This trial is designed to estimate the efficacy of a carfilzomib-based triplet in first or second relapse of multiple myeloma for subjects refractory to lenalidomide. The study is an open-label, phase 2 trial. Subjects may receive treatment until progression.

Myeloma disease status will be monitored locally for response and progression per International Myeloma Working Group (IMWG) criteria (Kumar et al, 2016) every 28 ± 7 days from cycle 1 day 1 until confirmed progressive disease (PD), death, lost to follow-up, or withdrawal of full consent (whichever occurs first), regardless of cycle duration, dose delays or treatment discontinuation. Subjects with a suspected complete response (CR) or better will have a bone marrow for minimal residual disease (MRD) assessment at 12 and 24 months (± 4 weeks) from start of treatment (unless a MRD assessment was performed within 4 months before planned assessment).

Subjects who end study drug(s) without confirmed PD are required to complete disease response assessments and report new anti-myeloma treatment every 28 ± 7 days until first subsequent anti-myeloma treatment, death, lost to follow-up, withdrawal of full consent, confirmed PD, or end of study, whichever occurs first. Subjects who discontinue treatment and either start new anti-myeloma treatment or have PD will enter long-term follow-up every 12 weeks until death or end of study.

Approximately one-third of subjects enrolled in the study will be in first relapse and two-thirds in second relapse.

This study will enroll adults ≥ 18 years of age with first or second relapse multiple myeloma.

Eligible subjects will have relapsed multiple myeloma after receiving 1 or 2 prior lines of therapy.

Subjects must be refractory to lenalidomide. Subjects may not have received prior pomalidomide. Prior exposure to a proteasome inhibitor is allowed. Subjects previously exposed to carfilzomib must have responded with at least a partial response to carfilzomib, must not have discontinued carfilzomib due to toxicity, may not have relapsed while receiving or within 60 days of the last dose of carfilzomib, and must have at least a 6 month carfilzomib treatment-free interval since their last dose of carfilzomib.

Subjects must have measurable disease per IMWG consensus criteria, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2, and at least partial response to 1 line of therapy.

Eligibility criteria: Inclusion Criteria

* Subject has provided informed consent prior to initiation of any study specific activities or procedures.
* Male or female subjects age ≥ 18 years
* First or second relapse of multiple myeloma by IMWG criteria (subjects refractory to the most recent line of therapy, excluding carfilzomib, are eligible)
* Refractory to lenalidamide
* Measurable disease with at least 1 of the following assessed within 28 days prior to enrollment:

  * IgG multiple myeloma: serum monoclonal protein (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 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
* Must have at least a PR to at least 1 line of prior therapy
* Prior therapy with proteasome inhibitors is allowed. Subjects receiving prior carfilzomib therapy must have achieved at least a PR, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and must have at least a 6 month carfilzomib treatment-free interval from their last dose of carfilzomib
* ECOG PS of 0 to 2

Exclusion Criteria

* Primary refractory multiple myeloma
* Waldenström macroglobulinemia
* Multiple myeloma of IgM subtype
* POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
* Plasma cell leukemia ( greater than 2.0 × 109/L circulating plasma cells by differential). If automated differential shows ≥ 20% of other cells, obtain manual differential to identify other cells.
* Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met)
* Previous diagnosis of amyloidosis associated with myeloma
* Myelodysplastic syndrome
* Toxicity requiring discontinuation of lenalidomide therapy
* Prior treatment with pomalidomide

Primary outcomes:
measure: Overall Response Rate (ORR) As Assessed by the Independent Review Committee (IRC) (PA DCO Only)
timeFrame: From day 1 cycle 1 until the PA DCO date of 30 November 2022; the median duration of KPd treatment as of the DCO was 32.8 weeks.
Secondary outcomes:
measure: Percentage of Participants With a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC (PA DCO Only)
timeFrame: Day 1 cycle 1 to month 12 (8 to 13 month window). PA DCO date of 30 November 2022; the median duration of KPd treatment as of the DCO was 32.8 weeks.
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: Day 1 cycle 1 up to approximately 60 months
measure: Number of Participants Achieving Minimal Residual Disease Negative MRD[-] Response
timeFrame: Day 1 cycle 1 to month 60
measure: Number of Participants With Sustained MRD[-]CR for at Least 12 Months as Assessed by the IRC
timeFrame: Day 1 cycle 1 to month 60
measure: Number of Participants With Sustained MRD[-]CR at Month 24 as Assessed by the IRC
timeFrame: Day 1 cycle 1 to month 26 (19 to 26 month window)
measure: Kaplan-Meier Estimate of Duration of Response as Assessed by the IRC
timeFrame: Day 1 cycle 1 to month 60
measure: Time to Response as Assessed by the IRC
timeFrame: Day 1 cycle 1 to month 60
measure: Kaplan-Meier Estimate of Progression Free Survival as Assessed by the IRC
timeFrame: Day 1 cycle 1 to month 60
measure: Kaplan-Meier Estimate of Overall Survival
timeFrame: Day 1 cycle 1 to month 60
measure: Number of Participants With Best Overall Confirmed Response of CR or Better as Assessed by the IRC
timeFrame: Day 1 cycle 1 to month 60
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers Denver Midtown
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Chicago Ridge
country: United States
facility: Affiliated Oncologists, LLC
state: Illinois
city: Saint Paul
country: United States
facility: Minnesota Oncology Hematology PA
state: Minnesota
city: Cincinnati
country: United States
facility: Oncology Hematology Care Incorporated
state: Ohio
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Austin
country: United States
facility: United States Oncology Regulatory Affairs Corporate Office
state: Texas
city: Austin
country: United States
facility: US Oncology Research Investigational Products Center
state: Texas
city: Dallas
country: United States
facility: Baylor Charles A Sammons Cancer Center at Dallas
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, Fort Worth
state: Texas
city: Tyler
country: United States
facility: Texas Oncology- Tyler
state: Texas
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
city: Roskilde
country: Denmark
facility: Sjaellands Universitetshospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre
city: Grenoble Cedex 9
country: France
facility: CHU Grenoble Alpes
city: Lille Cedex
country: France
facility: Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez
city: Nantes Cedex 1
country: France
facility: Centre Hospitalier Universitaire de Nantes
city: Pessac Cedex
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut Lévêque
city: Saint Quentin
country: France
facility: Centre Hospitalier de Saint Quentin
city: Strasbourg
country: France
facility: Clinique Sainte Anne
city: Toulouse cedex 9
country: France
facility: Institut Universitaire du Cancer Toulouse Oncopole
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Tubingen
country: Germany
facility: Universitatsklinikum Tubingen
city: Alexandroupoli
country: Greece
facility: University General Hospital of Evros-Alexandroupolis District
city: Athens
country: Greece
facility: General Hospital Evangelismos
city: Athens
country: Greece
facility: Alexandra Hospital
city: Ioannina
country: Greece
facility: University Hospital of Ioannina
city: Patra
country: Greece
facility: General University Hospital of Patras Panagia i Voithia
city: Thessaloniki
country: Greece
facility: Theagenion Cancer Hospital of Thessaloniki
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki Georgios Papanikolaou
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
city: Lecce
country: Italy
facility: Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza di Torino Ospedale Molinette
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
state: Castilla León
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Perrot A, Delimpasi S, Spanoudakis E, Frolund U, Belotti A, Oriol A, Moreau P, McFadden I, Xia Q, Arora M, Dimopoulos MA. An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib, pomalidomide, and dexamethasone (KPd): SELECT study. Leuk Lymphoma. 2024 Jun;65(6):833-842. doi: 10.1080/10428194.2024.2322030. Epub 2024 Mar 18.