Study to Evaluate Optimized Retreatment and Prolonged Therapy With Bortezomib

NCT ID: NCT01910987

Last Updated: 2017-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2016-02-29

Brief Summary

The objective of this study is to describe the effect of optimized retreatment with bortezomib in combination with dexamethasone followed by prolonged therapy with bortezomib, versus standard retreatment with bortezomib in combination with dexamethasone on progression free survival (PFS).

Detailed Description

This is an interventional, randomized (assignment to a group is happening by chance, like flipping a coin), open-label, parallel-group, event-driven, international, multicenter, Phase 3 study. This study has different phases: a pre-treatment phase, a treatment phase (which consists of an optimized retreatment period followed by a prolonged therapy period, or a standard retreatment period followed by a posttreatment period), and a long-term follow-up phase for survival up to the end of the study. Before the premature stopping of enrollment, the end of the study was event-driven, defined as 1 year after 186 events (an 'event' being defined as disease progression or death). Following the premature stopping of enrollment, effective 20 June 2014, the end of the study is defined as a maximum of 18 months after enrollment of the last patient in the study. After providing written informed consent, patients will be evaluated for eligibility during a 14-day pre-treatment period. The study doctor will carry out tests to see if the patient is suitable for this study, within the two weeks before receipt of the first dose of the study drugs. Once it has been determined that the patient is able to participate, he/she will be randomly assigned to 1 of 2 different bortezomib retreatment schedules. In this first randomization, patients will receive optimized retreatment or standard retreatment in a 2:1 ratio. Group A: optimized retreatment followed by prolonged therapy. Patients will start therapy with retreatment with 6 cycles of bortezomib and dexamethasone (two 21-day cycles followed by four 35-day cycles) followed by a second randomization in a 1:1 ratio to 1 of 2 prolonged therapy schedules with bortezomib alone (Group A1: once weekly for the first 4 weeks in 35-day cycles; or Group A2: once every other week). Group B: standard retreatment with eight 21-day bortezomib and dexamethasone cycles, followed by posttreatment follow-up every 6 weeks. During the retreatment phase, a series of tests will be done at the first day of each cycle. For patients in Group A the doctor will assess if the patient has responded to the treatment or not. Only if the patient responded, will he/she be able to continue in the prolonged therapy part of the study. At this time the patient will be randomized to one of the two groups (Group A1 or Group A2) in the prolonged therapy phase. During the prolonged therapy phase the disease status and the response to therapy will be evaluated every 6 weeks. This phase will continue until the disease progresses, in case there are unacceptable toxicities despite dose modifications. During the posttreatment period patients in group B will continue to be evaluated for disease status every 6 weeks until confirmed disease progression, when they start alternative multiple myeloma treatment, are withdrawn from the study, death or at the end of the study (a maximum of 18 months after the last patient is enrolled in the study), whichever occurs first. In case the patient discontinues bortezomib before disease progression during the treatment phase, he/she will be asked to complete the End of Study Visit procedures and will be evaluated every 6 weeks until confirmed disease progression, when they start alternative multiple myeloma treatment, are withdrawn from the study, death or at the end of the study (a maximum of 18 months after the last patient is enrolled in the study), whichever occurs first. All patients will have an End of Trial Visit performed 30 to 35 days after the last administration of bortezomib, or as soon as possible after bortezomib treatment is discontinued for patients receiving alternative multiple myeloma therapy. After confirmed disease progression or start of the first alternative multiple myeloma therapy, patients will enter the long-term follow-up phase for up to a maximum of 18 months after the last patient is enrolled in the study. During this phase, the patients will be contacted by at least a telephone call every other month to be followed up for the first alternative multiple myeloma therapy and survival. From the end of the study in countries where bortezomib is not commercially available for prolonged therapy or is not accessible (via a national program or access program) at that time, patients who in the opinion of the investigator would continue to benefit from prolonged therapy with bortezomib, will continue to be supplied with bortezomib until it is accessible in that particular country or for a period of 2 years, whichever occurs first. Before the premature stopping of enrollment, it was planned to enroll a target of 240 patients in this study.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

optimized retreatment, prolonged therapy

Patients will start therapy with retreatment with 6 cycles of bortezomib and dexamethasone (two 21-day cycles followed by four 35-day cycles) followed by a second randomization in a 1:1 ratio to 1 of 2 prolonged therapy schedules with bortezomib alone (Group A1: once weekly for the first 4 weeks in 35-day cycles; or Group A2: once every other week)

Group Type: EXPERIMENTAL

bortezomib (optimized retreatment)

Intervention Type: DRUG

Type= exact number, unit = mg/m2 body surface area, number = 1.3, form = powder for solution for injection, route = subcutaneous, injection on Days 1, 4, 8 and 11, every 21 days of cycle 1 and 2; injection on Days 1, 8, 15, 22, every 35 days for cycles 3 to 6; followed by injections on Days 1, 8, 15, 22 every 35 days (Group A1) or injections every other week (Group A2). Treatment will be stopped at confirmed disease progression

dexamethasone (optimized retreatment)

Intervention Type: DRUG

Type= exact number, unit = mg, number = 20, form = tablet, route = oral, intake on Days 1, 2, 4, 5, 8, 9, 11 and 12, every 21 days of cycle 1 and 2; intake on Days 1, 2, 8, 9, 15, 16, 22 and 23 every 35 days for cycles 3 to 6

standard retreatment

Current Standard of Care: Patients will start retreatment with eight 21-day bortezomib and dexamethasone cycles, followed by posttreatment follow-up every 6 weeks.

Group Type: OTHER

bortezomib (standard retreatment)

Intervention Type: DRUG

Type= exact number, unit = mg/m2 body surface area, number = 1.3, form = powder for solution for injection, route = subcutaneous, injection on Days 1,4,8,11, every 21 days for cycles 1 to 8 or until confirmed disease progression

dexamethasone (standard retreatment)

Intervention Type: DRUG

Type = exact number, unit = mg, number = 20, form = tablet, route= oral, intake on Days 1, 2, 4, 5, 8, 9, 11, 12, every 21 days for cycles 1 to 8 or until confirmed disease progression

Interventions

bortezomib (optimized retreatment)

Type= exact number, unit = mg/m2 body surface area, number = 1.3, form = powder for solution for injection, route = subcutaneous, injection on Days 1, 4, 8 and 11, every 21 days of cycle 1 and 2; injection on Days 1, 8, 15, 22, every 35 days for cycles 3 to 6; followed by injections on Days 1, 8, 15, 22 every 35 days (Group A1) or injections every other week (Group A2). Treatment will be stopped at confirmed disease progression

Intervention Type: DRUG

dexamethasone (optimized retreatment)

Type= exact number, unit = mg, number = 20, form = tablet, route = oral, intake on Days 1, 2, 4, 5, 8, 9, 11 and 12, every 21 days of cycle 1 and 2; intake on Days 1, 2, 8, 9, 15, 16, 22 and 23 every 35 days for cycles 3 to 6

Intervention Type: DRUG

bortezomib (standard retreatment)

Type= exact number, unit = mg/m2 body surface area, number = 1.3, form = powder for solution for injection, route = subcutaneous, injection on Days 1,4,8,11, every 21 days for cycles 1 to 8 or until confirmed disease progression

Intervention Type: DRUG

dexamethasone (standard retreatment)

Type = exact number, unit = mg, number = 20, form = tablet, route= oral, intake on Days 1, 2, 4, 5, 8, 9, 11, 12, every 21 days for cycles 1 to 8 or until confirmed disease progression

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Have received a bortezomib containing regimen in one of the previous line(s) of therapy and have shown at least PR to the previous bortezomib therapy.
• Have relapsed / progressed multiple myeloma following 1 or 2 previous lines of therapy as defined in the protocol.
• Have measurable secretory multiple myeloma: measurable disease for secretory multiple myeloma is defined by at least one of the following measurements: serum M protein greater than or equal to 1 g/dL (≥10g/L], urine M-protein of ≥200 mg/24 hours.
• Have an ECOG performance status of ≤2.
• Have a life expectancy estimated at screening of ≥6 months.

Exclusion Criteria

• Has received more than 2 previous lines of therapy for multiple myeloma or has received no previous bortezomib-containing regimen.
• Has been refractory to bortezomib, defined as either having progressed during bortezomib therapy or relapsed/progressed within 6 months after the last dose of bortezomib.
• Has oligosecretory or nonsecretory multiple myeloma.
• Has a history of a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Has peripheral neuropathy or neuropathic pain of grade 2 or greater intensity, as defined by the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI CTCAE), version 4.0.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag International NV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Heidelberg, , Germany

Mutlangen, , Germany

Osnabrück, , Germany

Rostock, , Germany

Haifa, , Israel

Nahariya, , Israel

Ramat Gan, , Israel

Apeldoorn, , Netherlands

Deventer, , Netherlands

Heerlen, , Netherlands

Tilburg, , Netherlands

Zwolle, , Netherlands

Fredrikstad, , Norway

Stavanger, , Norway

Trondheim, , Norway

Brzozów, , Poland

Chorzów, , Poland

Lodz, , Poland

Lublin, , Poland

Olsztyn, , Poland

Opole, , Poland

Słupsk, , Poland

Wroclaw, , Poland

Coimbra, , Portugal

Ponta Delgada, , Portugal

Porto, , Portugal

Borås, , Sweden

Falun, , Sweden

Huddinge, , Sweden

Stockholm, , Sweden

Adana, , Turkey (Türkiye)

Ankara, , Turkey (Türkiye)

Bursa, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Samsun, , Turkey (Türkiye)

Antwerp, , Belgium

Edegem, , Belgium

Haine-Saint-Paul, , Belgium

Hasselt, , Belgium

Sint-Niklaas, , Belgium

Turnhout, , Belgium

Yvoir, , Belgium

Helsinki, , Finland

Lahti, , Finland

Turku, , Finland

Lille, , France

Paris, , France

Périgueux, , France

Rennes, , France

Tours, , France

Cologne, , Germany

Dresden, , Germany

Trabzon, , Turkey (Türkiye)

Countries

Belgium; Finland; France; Germany; Israel; Netherlands; Norway; Poland; Portugal; Sweden; Turkey (Türkiye)

References

Terpos E, Gobbi M, Potamianou A, Lahaye M, Couturier C, Cavo M. Retreatment and prolonged therapy with subcutaneous bortezomib in patients with relapsed multiple myeloma: A randomized, controlled, phase III study. Eur J Haematol. 2018 Jan;100(1):10-19. doi: 10.1111/ejh.12937. Epub 2017 Oct 30.

Reference Type: DERIVED

PMID: 28801967 (View on PubMed)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=3334&filename=CR018796_EudraCT%20Full%20Data%20Set.pdf

A Randomized, Controlled, Phase 3 Study to Evaluate Optimized Retreatment and Prolonged Therapy With Bortezomib (VELCADE) in Patients With Multiple Myeloma in First or Second Relapse

Other Identifiers

26866138MMY3033

Identifier Type: OTHER

Identifier Source: secondary_id

2011-004795-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR018796

Identifier Type: -

Identifier Source: org_study_id