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

Multiple Myeloma Clinical Trial

— ARUMM  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02112175
• Other study ID #: CC-5013-MM-026
• Status: Completed
• Phase: Phase 3
• Start date: April 30, 2014
• Est. completion date: October 12, 2020

Study information

• Verified date: April 2021
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: October 12, 2020
• Est. primary completion date: October 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

1. Previously untreated and symptomatic multiple myeloma.

2. All 3 criteria (Durie, 2003) and at least one of the Creatinine Renal insufficiency Anemia lytic Bone lesions or osteoporosis criteria must be met.

3. Measurable disease by protein electrophoresis analyses.

4. 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.

5. 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.

6. Subjects must have cytogenetic (17 p deletion, and 4;14 translocation), ß-2 microglobulin and serum albumin (International Staging System) results from their initial diagnosis available at the time of screening. Related to the subject

7. Must understand and voluntarily sign the informed consent document prior to the conduct of any study related assessments/procedures,

8. Age = 65 years: if < 65 years of age, the subject must be non eligible for stem cell transplantation,

9. Eastern Cooperative Oncology Group performance status score = 2,

10. Able to adhere to the study visit schedules and other protocol requirements,

11. Females of Childbearing Potential must:

1. 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.

2. 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.

12. Male Subjects must:

1. 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.

2. Agree to not donate semen during Investigational Product therapy and for 28 days after end of study therapy.

13. All subjects must:

1. Have an understanding that the study medication could have a potential teratogenic risk.

2. Agree to abstain from donating blood while taking Investigational Product therapy and following discontinuation of Investigational Product therapy.

3. Agree not to share study medication with another person.

4. 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:

1. 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]).

2. 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.

3. Prior therapy with immunomodulating or immunosuppressive agents, or epigenetic or desoxyribonucleic acid modulating agents. Subjects who received investigational agents are also excluded.

4. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

5. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

6. Pregnant or lactating females.

7. Any of the following laboratory abnormalities:

Absolute neutrophil count < 1,000/L (1.0 x 10*9/L) Untransfused platelet count < 50,000 cells/L (50 x 10*9/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

8. Renal insufficiency (creatinine clearance < 30 mL/min by Cockcroft-Gault method) or actual creatinine clearance result, or renal failure requiring hemodialysis or peritoneal dialysis.

9. Prior history of malignancies including skin cancer, other than multiple myeloma.

10. Prior history of deep venous thrombosis or pulmonary embolus within 3 years of randomization.

11. Subjects who are unable or unwilling to undergo anti-thrombotic therapy.

12. Peripheral neuropathy of > Grade 2 severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.

13. Known Human Immunodeficiency Virus positivity or active infectious hepatitis, type A, B, or C.

14. Primary amyloidosis (immunoglobulin light chain) and myeloma complicated by amyloidosis.

15. Prior allogeneic or autologous stem cell transplantation.

16. 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

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Lenalidomide

Locations

Country	Name	City	State
Belgium	Centre Hospitalier EpiCURA - Clinique Louis Caty de Baudour	Baudour
Belgium	AZ-VUB	Brussels
Belgium	Grand Hopital de Charleroi	Charleroi
Belgium	Universitair Ziehenhuis Antwerpen	Edegem
Belgium	Centre Hospitalier de Jolimont-Lobbes	La Louvière-(Haine St-Paul)
Belgium	AZ Nikolaas	Sint-Niklaas
Belgium	Cliniques Universitaires UCL de Mont-Godine	Yvoir
France	CH Argenteuil Victor DupouyHematologie	Argenteuil
France	Centre Hospitalier de la cote basque	Bayonne
France	Hopital Jean Minjoz Hematologie	Besancon
France	Centre Hospitalier de Blois	Blois Cedex
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Hopital de Fleyriat	Bourg en Bresse cedex
France	Hopital A. MorvanHematologie	Brest cedex
France	CHU de la cote de Nacre	Caen
France	CHRU - Hotel Dieu	Clemont-Ferrand Cedex
France	Chu Estaing	Clermont Ferrand
France	Centre Hospitalier Sud Francilien - Site Gilles de Corbeil	Corbeil Essonnes
France	Hopital Henri Mondor	Creteil
France	Centre Hospitalier	Dunkerque
France	CHD Vendee	La Roche Sur Yon
France	CH Hematologie	Le Chesnay Cedex
France	Kremlin Bicetre	Le Kremlin bicetre CDX
France	Centre Jean BernardOnco-Hematologie	Le Mans
France	Centre Hospitalier Medecine interne	Le Mans cedex
France	CHRU Hopital Claude Huriez	Lile Cedax
France	CH - Hôpital Dupuytren	Limoges Cedex 1
France	Centre Hospitalier Regional Metz-Thionville Hopital de Mercy	Metz Cedex 03
France	CHU de Nimes	Nimes Cedex 9
France	CH La Source Onco-Hèmatologie	Orleans
France	Groupe Hospitalier Pitié- Salpétrière	Paris
France	Hopital Saint Louis	Paris
France	CH Perpignan - Hopital Saint-Jean	Perpignan
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	Centre Hospitalier de la Region d'Annecy	Pringy
France	CHRU Hopital sud Medecine Interne	Rennes cedex 02
France	Centre Hospitalier Yves Le Foll	St-Brieuc cedex 1
France	CHRU Hôpital de Hautepierre	Strasbourg
France	Hopital civil	Strasbourg
France	Institut Universitaire du Cancer IUCT - Oncopole	Toulouse Cedex
France	CHRU Hopital BretonneauOnco-hematologie	Tours cedex
France	CHRU Hôpitaux de Brabois	Vandoeuvre
Greece	Alexandra General Hospital of Athens	Athens
Greece	Laiko General Hospital of Athens	Athens
Greece	University of Patras	Patras
Greece	Theagenio Anticancer Hospital of Thessaloniki	Thessaloniki
Italy	Policlinico Sant'Orsola-Malpighi	Bologna
Italy	Spedali Civili Brescia	Brescia
Italy	Ospedale Ferrarotto	Catania
Italy	Clinica Ematologica, A.O.U. San Martino di Genova	Genova
Italy	Ematologia ed Immunologia, Azienda Ospedaliera Vito Fazzi di Lecce	Lecce
Italy	Unità Operativa di Oncoematologia, Ospedale di Matera	Matera
Italy	U.O. di Ematologia e Trapianto di Midollo Osseo	Milano
Italy	Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale	Napoli, Campania
Italy	Policlinico San Matteo Universita Di Pavia	Pavia 2
Italy	Ospedale Civile di Piacenza	Piacenza
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Policlinico Umberto I	Roma
Italy	Ospedale Sant'Eugenio	Rome
Italy	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	Dipartimento Medicina ed Oncologia Sperimentale - Divisione Universitaria di Ematologia Azienda Ospe	Torino
Italy	Ospedale Umberto I	Torrette Di Ancona
Italy	A.O. Universitaria Fondazione Macchi	Varese
Spain	Hospital Clinic Provincial de Barcelona	Barcelona
Spain	Hospital Sant Pau	Barcelona
Spain	Hospital virgen de la Arrixaca	El Palmar (murcia)
Spain	Hospital Virgenes de las Nieves	Granada
Spain	Hospital La Princesa	Madrid
Spain	Hospital Costa del Sol	Marbella
Spain	Hospital Central de Asturias	Oviedo
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Complejo Hospitalario de Santiago	Santiago de Compostela

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

Belgium,  France,  Greece,  Italy,  Spain, 

References & Publications (5)

Ailawadhi S, Jacobus S, Sexton R, Stewart AK, Dispenzieri A, Hussein MA, Zonder JA, Crowley J, Hoering A, Barlogie B, Orlowski RZ, Rajkumar SV. Disease and outcome disparities in multiple myeloma: exploring the role of race/ethnicity in the Cooperative Group clinical trials. Blood Cancer J. 2018 Jul 6;8(7):67. doi: 10.1038/s41408-018-0102-7. — View Citation

Dumontet C, Hulin C, Dimopoulos MA, Belch A, Dispenzieri A, Ludwig H, Rodon P, Van Droogenbroeck J, Qiu L, Cavo M, Van de Velde A, Lahuerta JJ, Allangba O, Lee JH, Boyle E, Perrot A, Moreau P, Manier S, Attal M, Roussel M, Mohty M, Mary JY, Civet A, Costa B, Tinel A, Gaston-Mathé Y, Facon T. A predictive model for risk of early grade = 3 infection in patients with multiple myeloma not eligible for transplant: analysis of the FIRST trial. Leukemia. 2018 Jun;32(6):1404-1413. doi: 10.1038/s41375-018-0133-x. Epub 2018 Apr 26. — View Citation

Gambella M, Omedé P, Spada S, Muccio VE, Gilestro M, Saraci E, Grammatico S, Larocca A, Conticello C, Bernardini A, Gamberi B, Troia R, Liberati AM, Offidani M, Rocci A, Palumbo A, Cavo M, Sonneveld P, Boccadoro M, Oliva S. Minimal residual disease by flow cytometry and allelic-specific oligonucleotide real-time quantitative polymerase chain reaction in patients with myeloma receiving lenalidomide maintenance: A pooled analysis. Cancer. 2019 Mar 1;125(5):750-760. doi: 10.1002/cncr.31854. Epub 2018 Dec 18. — View Citation

Jain T, Sonbol MB, Firwana B, Kolla KR, Almader-Douglas D, Palmer J, Fonseca R. High-Dose Chemotherapy with Early Autologous Stem Cell Transplantation Compared to Standard Dose Chemotherapy or Delayed Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis. Biol Blood Marrow Transplant. 2019 Feb;25(2):239-247. doi: 10.1016/j.bbmt.2018.09.021. Epub 2018 Sep 20. — View Citation

Pegourie B, Karlin L, Benboubker L, Orsini-Piocelle F, Tiab M, Auger-Quittet S, Rodon P, Royer B, Leleu X, Bareau B, Cliquennois M, Fuzibet JG, Voog E, Belhadj-Merzoug K, Decaux O, Rey P, Slama B, Leyronnas C, Zarnitsky C, Boyle E, Bosson JL, Pernod G; IFM Group. Apixaban for the prevention of thromboembolism in immunomodulatory-treated myeloma patients: Myelaxat, a phase 2 pilot study. Am J Hematol. 2019 Jun;94(6):635-640. doi: 10.1002/ajh.25459. Epub 2019 Apr 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Is defined as the time from the date of randomization to the date of death due to any cause.	Approximately 6 years
Secondary	Safety; Adverse Events (AE) [type, frequency, and severity of AEs, and relationship of AEs to investigational product (IP) SAEs, laboratory abnormalities, hospitalizations, and SPMs	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.	Approximately 6 years