Treatment With Velcade (Bortezomib) Plus Dexamethasone (VD) or VD Plus Cyclophosphamide or VD Plus Lenalidomide in Patients With Multiple Myeloma Stabilized After 4 Cycles of VD

NCT ID: NCT00908232

Last Updated: 2015-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 163 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2011-08-31

Brief Summary

The purpose of this study is to test the effectiveness and safety of adding cyclophosphamide or lenalidomide to the VD combination in the treatment of patients with multiple myeloma that have achieved a stable response after 4 initial cycles of treatment with VD. Multiple myeloma is the second most common cancer of the blood. Bortezomib disrupts the life cycle of the cell, affecting numerous biologic pathways, including those related to growth and survival of cancer cells.

Detailed Description

It has been shown that quality of response corresponds with clinical benefit. Stable disease is not regarded as a satisfactory result of therapy for relapsed and refractory multiple myeloma. However, there is no consensus if, when and how treatment should be continued or changed in the case of stable disease.

There are different strategies of achieving an optimal quality of response in relapsed and refractory multiple myeloma. One is to treat for a longer duration with one regimen. The alternative path can be a sequential approach adding another agent to the initial regimen depending on the outcome of therapy after a defined treatment period. These two principles will be evaluated in the present study.

Both Cyclophosphamide and Lenalidomide have proven to be efficacious in multiple myeloma and combinations of both agents with bortezomib and Dexamethasone have been shown to be active and tolerable.

In this study patients with relapsed/progressive or refractory multiple myeloma will start treatment with bortezomiib and Dexamethasone. Response will be evaluated after four cycles. Patients with complete, very good partial response or partial response will continue treatment as initiated. Patients with stable disease will either continue treatment with the bortezomib/Dexamethasone combination for another four cycles or will receive Cyclophosphamide or Lenalidomide as an additional third agent for another four cycles.

Patients with multiple myeloma that are refractory to or have relapsed/progressed after primary treatment for multiple myeloma will be enrolled in the study. All patients will receive a combination of bortezomib plus dexamethasone for a total of four cycles. Based on the response to this treatment, further study treatment is customized. Patients with a complete, a very good partial or a partial response will continue to receive bortezomib and Dexamethasone for a maximum additional four cycles, to an overall maximum of eight cycles. Patients achieving stable disease, as defined by International Myeloma Working Group 2006 (IMWG 2006) response criteria, will undergo a central randomisation to continue treatment with VD or VD plus cyclophosphamide or VD plus lenalidomide. Patients with progressive disease will go off study treatment. After randomisation, patients will receive therapy for up to four additional treatment cycles, to an overall maximum of eight cycles. Each cycle will consist of three weeks treatment. There will be a long-term follow-up period with monthly visits until relapse or progressive disease. Thereafter follow-up for survival will be continued by at least a phone call every other month. This will be performed for all patients until the last patient was treated and followed up for 1 year.

Safety will be assessed by the monitoring of adverse events, physical examination (including neurological/peripheral neurological examinations), pulmonary examinations, vital signs measurements, and clinical laboratory tests.

Patients will be treated in a 3-week cycle, up to a maximum of 8 cycles bortezomib 1.3 mg/m2 will be administered on day 1, 4, 8 and 11 as i.v. bolus infusion.

Dexamethasone 20 mg po will be administered on days 1, 2, 4, 5, 8, 9, 11, 12. Dexamethasone will be administered as 2 tables of 8 mg plus 1 tablet of 4 mg Cyclophosphamide 500 mg po will be administered as 10 tablets of 50 mg on day 1, 8, 15 Lenalidomide will be administered as once daily 10 mg tablet from day 1 to 14

Conditions

Multiple Myeloma

Study Design

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

Study Groups

Stable Disease: VD

Stable disease after 4 cycles bortezomib + dexamethasone: bortezomib 1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 in combination with dexamethasone 20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycle 1 to 8

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 for cycles 1 to 8

Dexamethasone

Intervention Type: DRUG

20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycles 1 to 8

Stable Disease: VDC

Stable disease after 4 cycles bortezomib + dexamethasone: bortezomib 1.3 mg/m2 IV bolus on Day 1, 4, 8 and 11 in combination with dexamethasone 20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycle 1 to 8 and cyclophosphamide 500 mg, orally daily, days 1, 8 and 15 for cycle 5 to 8

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

500 mg, p.o daily, days 1, 8 and 15 for cycles 5 to 8 cycles

Bortezomib

Intervention Type: DRUG

1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 for cycles 1 to 8

Dexamethasone

Intervention Type: DRUG

20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycles 1 to 8

Stable Disease: VDL

Stable disease after 4 cycles bortezomib + dexamethasone: bortezomib 1.3 mg/m2 IV bolus on Day 1, 4, 8 and 11 in combination with dexamethasone 20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycle 1 to 8 and lenalidomide 10 mg orally daily from day 1 to day 14 for cycle 5 to 8

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 for cycles 1 to 8

Dexamethasone

Intervention Type: DRUG

20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycles 1 to 8

Lenalidomide

Intervention Type: DRUG

10 mg orally daily, days 1-14 for cycles 5 to 8

Complete to Partial Response: VD

Complete, very good partial or partial response after 4 cycles bortezomib + dexamethasone: bortezomib 1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 in combination with dexamethasone 20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycle 1 to 8

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 for cycles 1 to 8

Dexamethasone

Intervention Type: DRUG

20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycles 1 to 8

Interventions

Cyclophosphamide

500 mg, p.o daily, days 1, 8 and 15 for cycles 5 to 8 cycles

Intervention Type: DRUG

Bortezomib

1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 for cycles 1 to 8

Intervention Type: DRUG

Dexamethasone

20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycles 1 to 8

Intervention Type: DRUG

Lenalidomide

10 mg orally daily, days 1-14 for cycles 5 to 8

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient has relapsed/progressed or is refractory for multiple myeloma following 1 previous line of therapy
• Measurable secretory multiple myeloma: measurable disease for secretory multiple myeloma is defined by at least one of the following measurements: serum monoclonal protein greater than or equal to 1 g/dl (> 10 gm/l) [10g/l], urine M-protein of ≥200 mg/24 hours
• Patient has a Karnofsky performance status of ≥ 60
• Patient has a life expectancy estimated at screening of at least 6 months
• Patient fulfills defined pretreatment laboratory requirements at and within 14 days before baseline

Exclusion Criteria

• Patient received more than 1 previous line of therapy for multiple myeloma
• Patient has known allergy or hypersensitivity to bortezomib, Dexamethasone and/or Cyclophosphamide and/or Lenalidomide or any of the constituent compounds such as boron, mannitol, or lactose
• Patient has oligosecretory or non-secretory multiple myeloma
• Patient received nitrosoureas or any other chemotherapy (including thalidomide), clarithromycin, interferon within 6 weeks before enrolment. Note: subjects can have received thalidomide or interferon as maintenance therapy, according to local standard of care
• Patient received corticosteroids (> 10 mg/day prednisone or equivalent) within 3 weeks before enrolment. Note: subjects can have received steroids (dexamethasone or equivalent) as maintenance therapy according to local standard of care. In addition, subjects can have received a cumulative dose of up to 160 mg of dexamethasone or equivalent as emergency therapy within 3 weeks prior to study entry.

• 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

Principal Investigators

Janssen-Cilag International NV Clinical Trial

Role: STUDY_DIRECTOR

Janssen-Cilag International NV

Locations

Bordeaux, , France

Le Mans, , France

Lille, , France

Tours, , France

Duisburg, , Germany

Essen, , Germany

Frankfurt (Oder), , Germany

Leipzig, , Germany

München, , Germany

Mÿnchen, , Germany

Oldenburg, , Germany

Ulm, , Germany

Athens, , Greece

Pátrai, , Greece

Budapest, , Hungary

Debrecen, , Hungary

Miskolc, , Hungary

Nyíregyháza, , Hungary

Szeged, , Hungary

Kaunas, , Lithuania

Klaipėda, , Lithuania

Vilnius Lt, , Lithuania

Bialystok, , Poland

Katowice, , Poland

Krakow, , Poland

Lodz, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Belgrade, , Serbia

Kamenitz, , Serbia

Niš, , Serbia

Novi Sad, , Serbia

Barcelona, , Spain

Madrid, , Spain

Toledo, , Spain

Valencia, , Spain

Ankara, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Bath, , United Kingdom

Edinburgh, , United Kingdom

London, , United Kingdom

Countries

France; Germany; Greece; Hungary; Lithuania; Poland; Serbia; Spain; Turkey (Türkiye); United Kingdom

References

Dimopoulos MA, Orlowski RZ, Facon T, Sonneveld P, Anderson KC, Beksac M, Benboubker L, Roddie H, Potamianou A, Couturier C, Feng H, Ataman O, van de Velde H, Richardson PG. Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma. Haematologica. 2015 Jan;100(1):100-6. doi: 10.3324/haematol.2014.112037. Epub 2014 Sep 26.

Reference Type: DERIVED

PMID: 25261096 (View on PubMed)

Other Identifiers

26866138MMY2045

Identifier Type: OTHER

Identifier Source: secondary_id

2007-001462-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR013165

Identifier Type: -

Identifier Source: org_study_id