ARROW2: A Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Sponsor

Amgen (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03859427

Collaborator

(none)

454

Enrollment

108

Locations

Arms

45.7

Anticipated Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Compare efficacy of 56 mg/m2 carfilzomib administered once-weekly in combination with lenalidomide and dexamethasone (KRd 56 mg/m2) to 27 mg/m2 carfilzomib administered twice-weekly in combination with lenalidomide and dexamethasone (KRd 27 mg/m2) in subjects with relapsed or refractory multiple myeloma (RRMM) with 1 to 3 prior lines of therapy.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Multiple Myeloma	Drug: Carfilzomib Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

454 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Open-label, Phase 3 Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (A.R.R.O.W.2)

Actual Study Start Date :

May 8, 2019

Anticipated Primary Completion Date :

Feb 28, 2023

Anticipated Study Completion Date :

Feb 28, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Carfilzomib once-weekly Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using once-weekly carfilzomib 56 mg/m2	Drug: Carfilzomib Once weekly IV over 30 minutes on day 1, 8 and 15 of each 28 day cycle. The dose will be 20 mg/m2 on cycle 1 day 1 and 56 mg/m2 beginning with cycle 1 day 8 and thereafter. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent. Drug: Lenalidomide Once daily orally 25 mg days 1 to 21 of each cycle. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent Drug: Dexamethasone Once daily orally or by IV 40 mg days 1, 8 and 15 of each cycle. Also day 22 of cycles 1 to 9. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent
Active Comparator: Carfilzomib twice-weekly Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using twice-weekly carfilzomib 27 mg/m2	Drug: Carfilzomib Twice weekly IV over 10 minutes on day 1, 2, 8, 9, 15 and 16 of each 28 day cycle. The dose will be 20 mg/m2 on cycle 1 days 1 and 2 and 27 mg/m2 beginning with cycle 1 day 8 and thereafter. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent. Drug: Lenalidomide Once daily orally 25 mg days 1 to 21 of each cycle. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent Drug: Dexamethasone Once daily orally or by IV 40 mg days 1, 8 and 15 of each cycle. Also day 22 of cycles 1 to 9. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent

Arm

Intervention/Treatment

Active Comparator: Carfilzomib once-weekly

Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using once-weekly carfilzomib 56 mg/m2

Drug: Carfilzomib

Once weekly IV over 30 minutes on day 1, 8 and 15 of each 28 day cycle. The dose will be 20 mg/m2 on cycle 1 day 1 and 56 mg/m2 beginning with cycle 1 day 8 and thereafter. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent.

Drug: Lenalidomide

Once daily orally 25 mg days 1 to 21 of each cycle. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent

Drug: Dexamethasone

Once daily orally or by IV 40 mg days 1, 8 and 15 of each cycle. Also day 22 of cycles 1 to 9. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent

Active Comparator: Carfilzomib twice-weekly

Carfilzomib, lenalidomide, dexamethasone (KRd) regimen using twice-weekly carfilzomib 27 mg/m2

Drug: Carfilzomib

Twice weekly IV over 10 minutes on day 1, 2, 8, 9, 15 and 16 of each 28 day cycle. The dose will be 20 mg/m2 on cycle 1 days 1 and 2 and 27 mg/m2 beginning with cycle 1 day 8 and thereafter. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent.

Drug: Lenalidomide

Once daily orally 25 mg days 1 to 21 of each cycle. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent

Drug: Dexamethasone

Once daily orally or by IV 40 mg days 1, 8 and 15 of each cycle. Also day 22 of cycles 1 to 9. 12 cycles or until progression, unacceptable toxicity, death, loss to follow up or withdrawal of consent

Outcome Measures

Primary Outcome Measures

Overall Response (OR) [Through study completion, an average of 14 months]
Defined as the best overall response of stringent complete response [sCR], complete response [CR], very good partial response [VGPR] and partial response [PR] per International Myeloma Working Group Uniform Response Criteria [IMWG-URC]

Secondary Outcome Measures

Progression free survival (PFS) [Through study completion, an average of 14 months]
Convenience [Through study completion, an average of 14 months]
As measured by the Patient-reported convenience with carfilzomib dosing schedule question
Subject incidence of treatment-emergent adverse events [Through study completion, an average of 14 months]
Additional efficacy parameter - Time to Response [Through study completion, an average of 14 months]
As measured by Time to Response (TTR)
Additional efficacy parameter - Duration of Response [Through study completion, an average of 14 months]
Duration of Response (DOR)
Additional efficacy parameter - Time to Progression [Through study completion, an average of 14 months]
Time to Progression (TTP)
Overall Survival [Through study completion, an average of 14 months]
MRD[-]CR rate [Through study completion, an average of 14 months]
Defined as achievement of CR or better by Independent Review Committee (IRC) per IMWG-URC and achievement of Minimal Residual Disease (MRD) negativity as assessed by next-generation sequencing method at a 10^ -5 threshold
MRD[-] status at 12 months [12 months]
Defined as achievement of Minimal Residual Disease (MRD) negativity at 12 months (+/- 4 weeks) from randomisation as assessed by next-generation sequencing method at a 10^ -5 threshold
Physical functioning and role functioning [Through study completion, an average of 14 months]
As measured by the Physical Functioning and Role Functioning scales of the European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30), a 30-item generic instrument for use in cancer subjects across tumor types
Treatment satisfaction as measured by the Satisfaction with Therapy (SWT) subscale of the Cancer Therapy Satisfaction Questionnaire (CTSQ) [4 months]
Cancer Therapy Satisfaction Questionnaire (CTSQ) - measures treatment satisfaction in individuals with cancer

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Multiple myeloma with documented relapse or progression after most recent myeloma treatment. Subjects refractory to the most recent line of therapy are eligible, unless last treatment contained proteasome inhibitor (PI) or lenalidomide and dexamethasone. Refractory is defined as disease that is nonresponsive or progresses within 60 days of last therapy.

Subjects must have at least PR to at least 1 line of prior therapy.

Subjects must have 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).

Prior therapy with a PI or the combination of lenalidomide and dexamethasone are allowed if the patient had at least a PR to the most recent treatment with a PI or lenalidomide and dexamethasone, neither PI or lenalidomide and dexamethasone containing treatment were ceased due to toxicity, the patient has not relapsed within 60 days of discontinuation of the PI or lenalidomide and dexamethasone containing treatment. A history of prior neuropathy is permitted if this was not grade 3, grade 4 or grade 2 with pain and if not resolved within the 14 days before enrollment, is less than or equal to grade 2 without pain. Patients are permitted to have received single agent lenalidomide as maintenance therapy within 60 days of enrollment.

Previous treatment with a lenalidomide and dexamethasone containing regimen is allowed, as long as the subject did not progress during the first 3 months after initiating lenalidomide and dexamethasone containing therapy.

Measurable disease with at least 1 of the following assessed within 21 days prior to randomization:

Immunoglobulin G (IgG) multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
Immunoglobulin A (IgA), Immunoglobulin D (IgD), Immunoglobulin E (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

Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 ≤ 2

Other inclusion criteria may apply

Exclusion Criteria:

Waldenström macroglobulinemia.

Multiple myeloma of Immunoglobulin M (IgM) subtype.

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

Uncontrolled hypertension, defined as a subject whose blood pressure is greater than or equal to 160 mmHg systolic or greater than or equal to 100 mmHg diastolic when taken in accordance with the European Society of Hypertension/European Society of Cardiology 2018 guidelines (Section 12.10; Williams et al, 2018).

Active congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, screening ECG with corrected QT interval (QTc) of > 470 msec, pericardial disease, or myocardial infarction within 4 months prior to randomization.

Calculated or measured creatinine clearance < 30 mL/min (calculation must be based on the Cockcroft and Gault formula) within 28 days prior to randomization.

Other exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert A Moss Oncology	Fountain Valley	California	United States	92708
2	Rocky Mountain Cancer Centers Denver Midtown	Denver	Colorado	United States	80218
3	Hartford HealthCare Cancer Institute at The Hospital of Central Connecticut	Plainville	Connecticut	United States	06062
4	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
5	Advocate Lutheran General Hospital	Park Ridge	Illinois	United States	60068
6	New York Oncology Hematology, PC	Albany	New York	United States	12208
7	Oncology Hematology Care Inc	Cincinnati	Ohio	United States	45242
8	Texas Oncology-Denton	Denton	Texas	United States	76201
9	US Oncology Research Investigational Products Center	Fort Worth	Texas	United States	76177
10	Oncology Consultants PA	Houston	Texas	United States	77030
11	Texas Oncology	San Antonio	Texas	United States	78229
12	United States Oncology Regulatory Affairs Corporate Office	The Woodlands	Texas	United States	77380
13	Universitaetsklinikum Salzburg	Salzburg		Austria	5020
14	University Multiprofile Hospital for Active Treatment Sveti Georgi EAD	Plovdiv		Bulgaria	4002
15	University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD	Sofia		Bulgaria	1431
16	Specialized Hospital for Active Treatment of Hematology Diseases EAD	Sofia		Bulgaria	1756
17	Fakultni nemocnice Brno	Brno		Czechia	625 00
18	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
19	Fakultni nemocnice Olomouc	Olomouc		Czechia	775 20
20	Vseobecna fakultni nemocnice v Praze	Praha 2		Czechia	128 08
21	Helsingin Yliopistollinen Keskussairaala	Helsinki		Finland	00290
22	Oulun Yliopistollinen Sairaala	Oulu		Finland	90220
23	Turun Yliopistollinen Keskussairaala	Turku		Finland	20521
24	Centre Hospitalier Universitaire de Nantes	Nantes		France	44000
25	Centre Hospitalier Universitaire Archet 2	Nice cedex 3		France	06202
26	Hopital Saint Louis	Paris		France	75010
27	Hopital Pitie-Salpetriere	Paris		France	75013
28	Centre Hospitalier Lyon Sud	Pierre-Benite		France	69495
29	Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie	Poitiers Cedex		France	86021
30	Centre Hospitalier Universitaire de Rennes	Rennes		France	35033
31	Institut de Cancerologie Strasbourg	Strasbourg		France	67033
32	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse cedex 9		France	31059
33	Centre Hospitalier Universitaire de Nancy - Hopital de Brabois	Vandoeuvre les Nancy Cedex		France	54511
34	Charité, Universitätsklinikum Berlin, Campus Benjamin Franklin	Berlin		Germany	12200
35	Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden	Dresden		Germany	01307
36	Universitatsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
37	Universitatsklinikum Koln	Köln		Germany	50924
38	Johannes Gutenberg Universitaet Mainz	Mainz		Germany	55131
39	University Hospital of Alexandroupolis	Alexandroupoli		Greece	68100
40	General Hospital Evangelismos	Athens		Greece	10676
41	Agios Savvas Anticancer Hospital	Athens		Greece	115 22
42	251 General Airforce Hospital	Athens		Greece	11525
43	Alexandra Hospital	Athens		Greece	11528
44	Metropolitan Hospital	Athens		Greece	18547
45	General University Hospital of Patras Panagia i Voithia	Patra		Greece	26504
46	Theagenion Cancer Hospital of Thessaloniki	Thessaloniki		Greece	54007
47	General Hospital of Thessaloniki Georgios Papanikolaou	Thessaloniki		Greece	57010
48	Nagoya City University Hospital	Nagoya-shi	Aichi	Japan	467-8602
49	Toyohashi Municipal Hospital	Toyohashi-shi	Aichi	Japan	441-8570
50	Tesshokai Kameda General Hospital	Kamogawa-shi	Chiba	Japan	296-8602
51	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka	Japan	811-1395
52	Ogaki Municipal Hospital	Ogaki-shi	Gifu	Japan	503-8502
53	National Hospital Organization Shibukawa Medical Center	Shibukawa-shi	Gunma	Japan	377-0280
54	Japanese Red Cross Society Himeji Hospital	Himeji-shi	Hyogo	Japan	670-8540
55	Hyogo College of Medicine Hospital	Nishinomiya-shi	Hyogo	Japan	663-8501
56	Hitachi Ltd Hitachi General Hospital	Hitachi-shi	Ibaraki	Japan	317-0077
57	University Hospital Kyoto Prefectural University of Medicine	Kyoto-shi	Kyoto	Japan	602-8566
58	National Hospital Organization Sendai Medical Center	Sendai-shi	Miyagi	Japan	983-8520
59	Niigata Cancer Center Hospital	Niigata-shi	Niigata	Japan	951-8566
60	National Hospital Organization Okayama Medical Center	Okayama-shi	Okayama	Japan	701-1192
61	Japanese Red Cross Osaka Hospital	Osaka-shi	Osaka	Japan	543-8555
62	Kindai University Hospital	Osakasayama-shi	Osaka	Japan	589-8511
63	Osaka University Hospital	Suita-shi	Osaka	Japan	565-0871
64	Saitama Medical Center	Kawagoe-shi	Saitama	Japan	350-8550
65	Tochigi Cancer Center	Utsunomiya-shi	Tochigi	Japan	320-0834
66	Juntendo University Hospital	Bunkyo-ku	Tokyo	Japan	113-8431
67	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-ku	Tokyo	Japan	135-8550
68	Japanese Red Cross Medical Center	Shibuya-ku	Tokyo	Japan	150-8935
69	Hospital of Lithuanian University of Health Sciences Kaunas Clinics Public Institution	Kaunas		Lithuania	50009
70	Vilnius University Hospital Santaros Clinic Public Institution	Vilnius		Lithuania	08661
71	VU Medisch Centrum	Amsterdam		Netherlands	1081 HV
72	Gelre Ziekenhuizen	Apeldoorn		Netherlands	7334 DZ
73	Spaarne Gasthuis	Hoofddorp		Netherlands	2134 TM
74	Fundeni Clinical Institute	Bucharest		Romania	022328
75	Institutul Clinic Fundeni	Bucharest		Romania	022328
76	Spitalul Clinic Coltea	Bucharest		Romania	030171
77	Spitalul Universitar de Urgenta Bucuresti	Bucharest		Romania	050098
78	Spitalul Clinic Colentina	Bucuresti		Romania	020125
79	Institutul Oncologic Prof Dr Ion Chiricuta	Cluj-Napoca		Romania	400015
80	Institutul Regional de Oncologie Iasi	Iasi		Romania	700483
81	Spitalul Clinic Dr Gavril Curteanu Oradea	Oradea		Romania	410469
82	Spitalul Clinic Judetean de Urgenta Sibiu	Sibiu		Romania	550245
83	Spitalul Clinic Municipal de Urgenta Timisoara	Timisoara		Romania	300079
84	Regional Clinical Hospital	Krasnoyarsk		Russian Federation	660022
85	Moscow State Budget Healthcare Institution City clinical Hospital 52 of Moscow Healthcare Department	Moscow		Russian Federation	123182
86	SBHI of Moscow city City clinical hospital na S P Botkin of Moscow city Healthcare department	Moscow		Russian Federation	125284
87	SBHI of Republic of Karelia Republic Hosiptal n a V A Baranov	Petrozavodsk		Russian Federation	185019
88	Federal centre of heart, blood and endocrinology Almazova	Saint Petersburg		Russian Federation	197341
89	State Budget Educational Institution of High Professional Skills Samara State Medical University	Samara		Russian Federation	443079
90	Univerzitna nemocnica Bratislava, Nemocnica sv Cyrila a Metoda	Bratislava		Slovakia	851 07
91	Hospital Universitari Son Espases	Palma de Mallorca	Baleares	Spain	07010
92	Hospital Clinico Universitario de Salamanca	Salamanca	Castilla León	Spain	37007
93	Hospital Universitari Germans Trias i Pujol	Badalona	Cataluña	Spain	08916
94	Hospital Clinic i Provincial de Barcelona	Barcelona	Cataluña	Spain	08036
95	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcon	Madrid	Spain	28223
96	Clinica Universidad de Navarra	Pamplona	Navarra	Spain	31008
97	Falu Lasarett	Falun		Sweden	791 82
98	Sahlgrenska Universitetssjukhuset	Goteborg		Sweden	413 45
99	Hallands Sjukhus Halmstad	Halmstad		Sweden	301 85
100	Sunderby Sjukhus	Lulea		Sweden	971 80
101	Skanes Universitetssjukhus	Lund		Sweden	221 85
102	Gazi Universitesi Saglik Arastirma ve Uygulama Merkezi Gazi Hastanesi	Ankara		Turkey	06560
103	Ankara Universitesi Tip Fakultesi Cebeci Arastirma ve Uygulama Hastanesi	Ankara		Turkey	06590
104	Istanbul Universitesi Istanbul Tip Fakultesi	Istanbul		Turkey	34093
105	Bagcilar Medipol Mega Universite Hastanesi	Istanbul		Turkey	34214
106	Istanbul Florence Nightingale Hastanesi	Istanbul		Turkey	34387
107	Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi	Izmir		Turkey	35340
108	Erciyes Universitesi Tip Fakultesi Mehmet Kemal Dedeman Hematoloji-Onkoloji Hastanesi	Kayseri		Turkey	38039

Sponsors and Collaborators

Amgen

Investigators

Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

AmgenTrials clinical trials website

Publications

None provided.

Responsible Party:

Amgen

ClinicalTrials.gov Identifier:

NCT03859427

Other Study ID Numbers:

20180015

First Posted:

Mar 1, 2019

Last Update Posted:

Mar 3, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Amgen

Bone Marrow Cancer

Additional relevant MeSH terms:

Multiple Myeloma

Neoplasms, Plasma Cell

Dexamethasone

Lenalidomide

Study Results

No Results Posted as of Mar 3, 2022