ARUMM: Lenalidomide vs Placebo Maintenance Therapy Following Melphalan Prednisone Velcade® Induction Therapy in NDMM

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT02112175

Collaborator

(none)

Enrollment

Locations

Arm

77.4

Actual Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and efficacy of Lenalidomide versus Placebo maintenance following melphalan, prednisone and velcade induction therapy in newly diagnosed multiple myeloma.

After the study is unblinded, subjects in treatment Arm A (Len 10 mg) will remain on study therapy at the Investigator's discretion and subjects in treatment Arm B (placebo), will be discontinued from study treatment. Subjects who discontinued from study treatment for any reason will enter the LTFU Phase.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Lenalidomide	Phase 3

Detailed Description

The planned total number of evaluable subjects for PFS was approximately 351 (234 in the lenalidomide treatment arm; 117 in the placebo treatment arm) and the study will be conducted in European countries. However, due to the significant enrollment challenges and the changes in the NDMM treatment practices in subjects who are not eligible for transplant, such as the recent approval of Revlimid in NDMM setting, the DMC recommended to close study enrollment. Study enrollment was closed on 12 October 2015.

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 3B, Randomized Trail of Revlimid® (Lenalidomide) Versus Placebo Maintenance Therapy Following Melphalan Prednisone Velcade (Bortezomib) Induction Therapy In Newly Diagnosed Multiple Myeloma

Actual Study Start Date :

Apr 30, 2014

Actual Primary Completion Date :

Oct 12, 2020

Actual Study Completion Date :

Oct 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide Treatment Arm A: lenalidomide 10 mg/day orally from Days 1 to 21; given in 28-day cycles for up to disease progression.	Drug: Lenalidomide

Arm

Intervention/Treatment

Experimental: Lenalidomide

Treatment Arm A: lenalidomide 10 mg/day orally from Days 1 to 21; given in 28-day cycles for up to disease progression.

Drug: Lenalidomide

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [Approximately 6 years]
Is defined as the time from the date of randomization to the date of death due to any cause.

Secondary Outcome Measures

Safety; Adverse Events (AE) [type, frequency, and severity of AEs, and relationship of AEs to investigational product (IP) SAEs, laboratory abnormalities, hospitalizations, and SPMs [Approximately 6 years]
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

Related to initial diagnosis and prior Melphalan Prednisone Velcade (MPV) induction therapy

Previously untreated and symptomatic multiple myeloma.
All 3 criteria (Durie, 2003) and at least one of the Creatinine Renal insufficiency Anemia lytic Bone lesions or osteoporosis criteria must be met.
Measurable disease by protein electrophoresis analyses.
All subjects must be treated with a minimum of 6 and a maximum of 9 cycles of MPV induction regimen, and must have achieved at least Partial Response as best overall response and maintained at Melphalan Prednisone Velcade discontinuation. If a subject achieves Complete Response prior to at least 6 cycles, the subject will be eligible, but a minimum of 6 cycles must be administered otherwise.
Subjects must not have received any prior anti-myeloma chemotherapy or any investigational agent except 6-9 cycles of induction therapy with Melphalan Prednisone Velcade.
Subjects must have cytogenetic (17 p deletion, and 4;14 translocation), β-2 microglobulin and serum albumin (International Staging System) results from their initial diagnosis available at the time of screening.

Related to the subject

Must understand and voluntarily sign the informed consent document prior to the conduct of any study related assessments/procedures,
Age ≥ 65 years: if < 65 years of age, the subject must be non eligible for stem cell transplantation,
Eastern Cooperative Oncology Group performance status score ≤ 2,
Able to adhere to the study visit schedules and other protocol requirements,
Females of Childbearing Potential must:
Have two negative pregnancy tests as verified by the study doctor prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy. This applies even if the subject practices true abstinence2 from heterosexual contact.
Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting Investigational Product, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
Male Subjects must:
Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female or childbearing potential while participating in the study, during dose interruptions and for at least 28 days following Investigational Product discontinuation, even if he has undergone a successful vasectomy.
Agree to not donate semen during Investigational Product therapy and for 28 days after end of study therapy.
All subjects must:
Have an understanding that the study medication could have a potential teratogenic risk.
Agree to abstain from donating blood while taking Investigational Product therapy and following discontinuation of Investigational Product therapy.
Agree not to share study medication with another person.
All female of childbearing potential and male subjects must be counseled about pregnancy precautions and risks of fetal exposure.

Exclusion Criteria:

The presence of any of the following will exclude the subject from the study enrollment:

Previous treatment with anti-myeloma therapy other than the required 6-9 cycles of Melphalan Prednisone Velcade induction therapy (does not include local radiotherapy, bisphosphonates, or a single short course of steroid [ie, less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of randomization]).
Subjects who didn't achieve Partial Response or better after getting at least 6 cycles of Melphalan Prednisone Velcade and at the end of Melphalan Prednisone Velcade whatever the overall response are not eligible.
Prior therapy with immunomodulating or immunosuppressive agents, or epigenetic or desoxyribonucleic acid modulating agents. Subjects who received investigational agents are also excluded.
Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
Pregnant or lactating females.
Any of the following laboratory abnormalities:

Absolute neutrophil count < 1,000/L (1.0 x 109/L) Untransfused platelet count < 50,000 cells/L (50 x 109/L) Serum glutamic oxaloacetic transaminase/alanine aminotransferase or serum glutamic pyruvic transaminase/alanine aminotransferase

3.0 x upper limit of normal Serum bilirubin levels > 1.5 x upper limit of normal

Renal insufficiency (creatinine clearance < 30 mL/min by Cockcroft-Gault method) or actual creatinine clearance result, or renal failure requiring hemodialysis or peritoneal dialysis.
Prior history of malignancies including skin cancer, other than multiple myeloma.
Prior history of deep venous thrombosis or pulmonary embolus within 3 years of randomization.
Subjects who are unable or unwilling to undergo anti-thrombotic therapy.
Peripheral neuropathy of > Grade 2 severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
Known Human Immunodeficiency Virus positivity or active infectious hepatitis, type A, B, or C.
Primary amyloidosis (immunoglobulin light chain) and myeloma complicated by amyloidosis.
Prior allogeneic or autologous stem cell transplantation.
Significant active cardiac disease within the previous 6 months including:

New York Heart Association class II-IV congestive heart failure Unstable angina or angina requiring surgical or medical intervention Myocardial infarction

Any condition that confounds the ability to interpret data from the study.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour	Baudour	Belgium	7331
2	AZ-VUB	Brussels	Belgium	1090
3	Grand Hopital de Charleroi	Charleroi	Belgium	6000
4	Universitair Ziehenhuis Antwerpen	Edegem	Belgium	2650
5	Centre Hospitalier de Jolimont-Lobbes	La Louvière-(Haine St-Paul)	Belgium	7100
6	AZ Nikolaas	Sint-Niklaas	Belgium	9100
7	Cliniques Universitaires UCL de Mont-Godine	Yvoir	Belgium	5530
8	CH Argenteuil Victor DupouyHematologie	Argenteuil	France	95100
9	Centre Hospitalier de la cote basque	Bayonne	France	64109
10	Hopital Jean Minjoz Hematologie	Besancon	France	25000
11	Centre Hospitalier de Blois	Blois Cedex	France	41016
12	Polyclinique Bordeaux Nord Aquitaine	Bordeaux	France	33300
13	Hopital de Fleyriat	Bourg en Bresse cedex	France	01012
14	Hopital A. MorvanHematologie	Brest cedex	France	29609
15	CHU de la cote de Nacre	Caen	France	14000
16	CHRU - Hotel Dieu	Clemont-Ferrand Cedex	France	63003
17	Chu Estaing	Clermont Ferrand	France	63000
18	Centre Hospitalier Sud Francilien - Site Gilles de Corbeil	Corbeil Essonnes	France	91106
19	Hopital Henri Mondor	Creteil	France	94010
20	Centre Hospitalier	Dunkerque	France	59385
21	CHD Vendee	La Roche Sur Yon	France	85000
22	CH Hematologie	Le Chesnay Cedex	France	78157
23	Kremlin Bicetre	Le Kremlin bicetre CDX	France	942975
24	Centre Hospitalier Medecine interne	Le Mans cedex	France	72037
25	Centre Jean BernardOnco-Hematologie	Le Mans	France	72000
26	CHRU Hopital Claude Huriez	Lile Cedax	France	59037
27	CH - Hôpital Dupuytren	Limoges Cedex 1	France	87042
28	Centre Hospitalier Regional Metz-Thionville Hopital de Mercy	Metz Cedex 03	France	57038
29	CHU de Nimes	Nimes Cedex 9	France	30029
30	CH La Source Onco-Hèmatologie	Orleans	France	45000
31	Hopital Saint Louis	Paris	France	75010
32	Groupe Hospitalier Pitié- Salpétrière	Paris	France	75651
33	CH Perpignan - Hopital Saint-Jean	Perpignan	France	66046
34	Centre Hospitalier Lyon Sud	Pierre Bénite	France	69495
35	Centre Hospitalier de la Region d'Annecy	Pringy	France	74374
36	CHRU Hopital sud Medecine Interne	Rennes cedex 02	France	35056
37	Centre Hospitalier Yves Le Foll	St-Brieuc cedex 1	France	22027
38	Hopital civil	Strasbourg	France	67091
39	CHRU Hôpital de Hautepierre	Strasbourg	France	67098
40	Institut Universitaire du Cancer IUCT - Oncopole	Toulouse Cedex	France	31059
41	CHRU Hopital BretonneauOnco-hematologie	Tours cedex	France	37044
42	CHRU Hôpitaux de Brabois	Vandoeuvre	France
43	Laiko General Hospital of Athens	Athens	Greece	11527
44	Alexandra General Hospital of Athens	Athens	Greece	11528
45	University of Patras	Patras	Greece	26500
46	Theagenio Anticancer Hospital of Thessaloniki	Thessaloniki	Greece	540 07
47	Policlinico Sant'Orsola-Malpighi	Bologna	Italy	40138
48	Spedali Civili Brescia	Brescia	Italy	25123
49	Ospedale Ferrarotto	Catania	Italy	95124
50	Clinica Ematologica, A.O.U. San Martino di Genova	Genova	Italy	16132
51	Ematologia ed Immunologia, Azienda Ospedaliera Vito Fazzi di Lecce	Lecce	Italy	73100
52	Unità Operativa di Oncoematologia, Ospedale di Matera	Matera	Italy	75100
53	U.O. di Ematologia e Trapianto di Midollo Osseo	Milano	Italy	20132
54	Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale	Napoli, Campania	Italy	80131
55	Policlinico San Matteo Universita Di Pavia	Pavia 2	Italy	27100
56	Ospedale Civile di Piacenza	Piacenza	Italy	29100
57	Arcispedale Santa Maria Nuova	Reggio Emilia	Italy	42100
58	Policlinico Umberto I	Roma	Italy	00161
59	Ospedale Sant'Eugenio	Rome	Italy	00144
60	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo	Italy	71013
61	Dipartimento Medicina ed Oncologia Sperimentale - Divisione Universitaria di Ematologia Azienda Ospe	Torino	Italy	10126
62	Ospedale Umberto I	Torrette Di Ancona	Italy	60020
63	A.O. Universitaria Fondazione Macchi	Varese	Italy	21100
64	Hospital Sant Pau	Barcelona	Spain	08025
65	Hospital Clinic Provincial de Barcelona	Barcelona	Spain	08036
66	Hospital virgen de la Arrixaca	El Palmar (murcia)	Spain	30120
67	Hospital Virgenes de las Nieves	Granada	Spain	18014
68	Hospital La Princesa	Madrid	Spain	28006
69	Hospital Costa del Sol	Marbella	Spain	29603
70	Hospital Central de Asturias	Oviedo	Spain	33006
71	Clinica Universitaria de Navarra	Pamplona	Spain	31008
72	Hospital Universitario de Salamanca	Salamanca	Spain	37007
73	Complejo Hospitalario de Santiago	Santiago de Compostela	Spain	15706