SELECT: Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet

Sponsor

Amgen (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04191616

Collaborator

(none)

Enrollment

Locations

Arm

64.7

Anticipated Duration (Months)

1.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Multiple Myeloma	Drug: Carfilzomib Drug: Dexamethasone Drug: Pomalidomide	Phase 2

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 antimyeloma 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 (PR) to 1 line of therapy.

Study Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 6, 2020

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

Dec 27, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carfilzomib combined with pomalidomide and dexamethasone Carfilzomib, pomalidomide, and dexamethasone (KPd)	Drug: Carfilzomib Carfilzomib will be administered intravenously over 30 ± 5 minutes, on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression. A dose of 20 mg/m^2 will be administered on day 1 of cycle 1. All subsequent doses will be 56 mg/m^2. The frequency of carfilzomib administration will be reduced to day 1 and 15 per cycle starting with cycle 13 and continued until progression or end of study. Other Names: Kyprolis Drug: Dexamethasone Dexamethasone will be administered at least 30 minutes, but no more than 4 hours prior to carfilzomib on days of carfilzomib administration. Dexamethasone will be administered at a dose of 40 mg on days 1, 8, 15, and 22 of each 28-day cycle up to progression during cycles 1 to 12. Dexamethasone will be administered at a dose of 20 mg on days 1 and 15 of each 28-day cycle up to progression during cycles 13 onward. For subjects more than or equal to 75 years of age, the dose will be 20 mg during cycles 1 through 12 and 10 mg from cycles 13 onward. Other Names: Decadron, Ozurdex, DexPak 6, 10, 13 Day, ReadySHarp, LoCort, Maxidex Drug: Pomalidomide Pomalidomide dose will be 4 mg per day orally on days 1 to 21 of each cycle until progression. Other Names: Pomalyst

Arm

Intervention/Treatment

Experimental: Carfilzomib combined with pomalidomide and dexamethasone

Carfilzomib, pomalidomide, and dexamethasone (KPd)

Drug: Carfilzomib

Carfilzomib will be administered intravenously over 30 ± 5 minutes, on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression. A dose of 20 mg/m^2 will be administered on day 1 of cycle 1. All subsequent doses will be 56 mg/m^2. The frequency of carfilzomib administration will be reduced to day 1 and 15 per cycle starting with cycle 13 and continued until progression or end of study.

Other Names:

Kyprolis

Drug: Dexamethasone

Dexamethasone will be administered at least 30 minutes, but no more than 4 hours prior to carfilzomib on days of carfilzomib administration. Dexamethasone will be administered at a dose of 40 mg on days 1, 8, 15, and 22 of each 28-day cycle up to progression during cycles 1 to 12. Dexamethasone will be administered at a dose of 20 mg on days 1 and 15 of each 28-day cycle up to progression during cycles 13 onward. For subjects more than or equal to 75 years of age, the dose will be 20 mg during cycles 1 through 12 and 10 mg from cycles 13 onward.

Other Names:

Decadron, Ozurdex, DexPak 6, 10, 13 Day, ReadySHarp, LoCort, Maxidex

Drug: Pomalidomide

Pomalidomide dose will be 4 mg per day orally on days 1 to 21 of each cycle until progression.

Other Names:

Pomalyst

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [60 months]
Objective response defined as the best overall confirmed response of partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) by Independent Review Committee (IRC) per International Myeloma Working Group Uniform Response Criteria (IMWG-URC).

Secondary Outcome Measures

Number of participants with a minimal residual disease negative complete response (MRD[-]CR) in participants with multiple myeloma at first or second relapse after treatment with lenalidomide [Up to 13 months]
MRD[-]CR at a sensitivity of 10^-5 using next generation sequencing (NGS)-based method in the bone marrow at 12 months +/-4 weeks from start of treatment.
Subject incidence of treatment-emergent adverse event [Up to 60 Months]
Describe the safety and tolerability of carfilzomib combined dexamethasone and pomalidomide.
Number of participants who achieve minimal residual disease negative (MRD[-]) after treatment with pomalidomide and dexamethasone (KPd) [Up to 60 months]
MRD(-) at a sensitivity of 10^-5 using next generation sequencing (NGS)-based method in the bone marrow.
Number of participants with sustained MRD[-]CR [26 months]
Sustained MRD[-]CR response at a sensitivity of 10^-5 using NGS-based method in the bone marrow defined as subjects that maintain MRD[-]CR 12 months or more after achieving MRD[-]CR status, disregarding when the first MRD[-]CR was reached.
Number of participants with sustained MRD[-]CR [24 months]
Sustained MRD[-]CR response at a sensitivity of 10^-5 using NGS-based method in the bone marrow at 24 months ± 4 weeks from start of treatment and calculated only within the subjects who reached MRD[-]CR in the time window for key secondary endpoint assessment.
Overall response rate at 12 month landmark [12 months]
Estimate a landmark overall response by 12 months, defined as the best overall confirmed response of partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) by 12 months from start of treatment.
Duration of response [From start of treatment until disease progression or death from any cause (approximately 5 years)]
Estimate duration of response, defined as time from first date of partial response (PR) or better to date of disease progression or death due to any cause.
Time to response [From start of treatment until disease progression or death from any cause (approximately 5 years)]
Estimate time to response, defined as time from start of treatment to first date of partial response (PR) or better.
Progression-free survival (PFS) [From start of treatment until disease progression or death from any cause (approximately 5 years)]
Estimate Progression-free survival (PFS) defined as time from start of treatment until progression or death from any cause.
Overall survival (OS) [From start of treatment until disease progression or death from any cause (approximately 5 years)]
Estimate Overall Survival (OS), defined as time from start of treatment until death from any cause.
Best overall confirmed response of complete response (CR) or better [Up to 60 months]
Estimate complete response (CR) rate of carfilzomib, pomalidomide and dexamethasone (KPd) cohort.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 International Myeloma Working Group (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 partial response (PR) to at least 1 line of prior therapy
Prior therapy with PI 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
Eastern Cooperative Oncology Group (ECOG) Performance Status (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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
2	Rocky Mountain Cancer Centers Denver Midtown	Denver	Colorado	United States	80218
3	Yale Cancer Center	New Haven	Connecticut	United States	06510
4	Affiliated Oncologists, LLC	Chicago Ridge	Illinois	United States	60415
5	Minnesota Oncology Hematology PA	Saint Paul	Minnesota	United States	55102
6	Oncology Hematology Care Incorporated	Cincinnati	Ohio	United States	45236
7	Texas Oncology - Austin Midtown	Austin	Texas	United States	78705
8	United States Oncology Regulatory Affairs Corporate Office	Austin	Texas	United States	78705
9	US Oncology Research Investigational Products Center	Austin	Texas	United States	78705
10	Baylor Charles A Sammons Cancer Center at Dallas	Dallas	Texas	United States	75246
11	Texas Oncology, Fort Worth	Fort Worth	Texas	United States	76104
12	Texas Oncology- Tyler	Tyler	Texas	United States	75702
13	Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
14	Aalborg Universitetshospital	Aalborg		Denmark	9000
15	Aarhus Universitetshospital	Aarhus N		Denmark	8200
16	Sjaellands Universitetshospital	Roskilde		Denmark	4000
17	Vejle Sygehus	Vejle		Denmark	7100
18	North Estonia Medical Centre	Tallinn		Estonia	13419
19	CHU Grenoble Alpes	Grenoble Cedex 9		France	38043
20	Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez	Lille Cedex		France	59037
21	Centre Hospitalier Universitaire de Nantes	Nantes Cedex 1		France	44093
22	Centre Hospitalier Universitaire de Bordeaux - Hôpital Haut Lévêque	Pessac Cedex		France	33604
23	Centre Hospitalier de Saint Quentin	Saint Quentin		France	02321
24	Clinique Sainte Anne	Strasbourg		France	67000
25	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse cedex 9		France	31059
26	Klinikum Chemnitz gGmbH	Chemnitz		Germany	09113
27	Asklepios Klinik Altona	Hamburg		Germany	22763
28	Universitätsklinikum Münster	Münster		Germany	48149
29	Universitatsklinikum Tubingen	Tubingen		Germany	72076
30	University General Hospital of Evros-Alexandroupolis District	Alexandroupoli		Greece	68100
31	General Hospital Evangelismos	Athens		Greece	10676
32	Alexandra Hospital	Athens		Greece	11528
33	University Hospital of Ioannina	Ioannina		Greece	45500
34	General University Hospital of Patras Panagia i Voithia	Patra		Greece	26504
35	Theagenion Cancer Hospital of Thessaloniki	Thessaloniki		Greece	54007
36	General Hospital of Thessaloniki Georgios Papanikolaou	Thessaloniki		Greece	57010
37	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona	Ancona		Italy	60126
38	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia		Italy	25123
39	Azienda Unita Sanitaria Locale LE Presidio Ospedaliero Vito Fazzi Polo Oncologico Giovanni Paolo II	Lecce		Italy	73100
40	Policlinico Universitario Agostino Gemelli	Roma		Italy	00168
41	Azienda Ospedaliera Citta della Salute e della Scienza di Torino Ospedale Molinette	Torino		Italy	10126
42	Hospital Clinico Universitario de Salamanca	Salamanca	Castilla León	Spain	37007
43	Hospital Universitari Germans Trias i Pujol	Badalona	Cataluña	Spain	08916
44	Hospital Clinic i Provincial de Barcelona	Barcelona	Cataluña	Spain	08036
45	Hospital Universitari i Politecnic La Fe	Valencia	Comunidad Valenciana	Spain	46026
46	Hospital Universitario 12 de Octubre	Madrid		Spain	28041