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

NCT00908232 | Completed Phase 2 Results DMC

• 3 other identifiers: CR01316526866138MMY20452007-001462-33
• Study Type: interventional
• Target: 163
• Locations: 10 countries
• Sites: 42

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.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; bortezomib; hematology; bone marrow cancer; immunoglobulin; refractory; progression; dexamethasone; lenalidomide; cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Overall Best Confirmed Response

  Overall Best Confirmed Response is the best Overall Response Rate with borezomib-dexamathasone (+/-cyclophosphamide or lenalidomide) recorded between baseline and end of treatment. Response was assessed using the International Myeloma working Group (IMWG) Uniform Response Criteria and validated by an Independent Monitoring Committee.

  Prior to treatment at day 1 of each cycle and at the end of treatment (day 21 of cycle 8), up to 168 days

Secondary Outcomes (5)

• Median Time to First Confirmed Response

  At Day 1 of each treatment cycle, at the End of Treatment visit until there is evidence of Progressive Disease or relapse from Complete Response (CR), up to 168 days

• Progression Free Survival

  At Day 1 of each treatment cycle, at the End of Treatment visit until there is evidence of Progressive Disease or relapse from Complete Response (CR). Median Follow-Up of 16.9 months

• Time to Progression

  At Day 1 of each treatment cycle, at the End of Treatment visit until there is evidence of Progressive Disease or relapse from Complete Response (CR), Median Follow-up of 16.9 months

• One Year Survival

  At each visit from baseline to end of treatment. After treatment, monthly visit until progression or relapse or until the start of alternative MMY therapy, up to 1 year

• Overall Survival

  At each visit from baseline to end of treatment. After treatment, monthly visit until progression or relapse or until the start of alternative MMY therapy. Further follow up by monthly phone call until the last patient was treated and followed for 1 year

Study Arms (4)

Stable Disease: VD

EXPERIMENTAL

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

Drug: Bortezomib; Drug: Dexamethasone

Stable Disease: VDC

EXPERIMENTAL

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

Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone

Stable Disease: VDL

EXPERIMENTAL

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

Drug: Bortezomib; Drug: Dexamethasone; Drug: Lenalidomide

Complete to Partial Response: VD

EXPERIMENTAL

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

Drug: Bortezomib; Drug: Dexamethasone

Interventions

Cyclophosphamide DRUG

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

Stable Disease: VDC

Bortezomib DRUG

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

Complete to Partial Response: VD; Stable Disease: VD; Stable Disease: VDC; Stable Disease: VDL

Dexamethasone DRUG

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

Complete to Partial Response: VD; Stable Disease: VD; Stable Disease: VDC; Stable Disease: VDL

Lenalidomide DRUG

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

Stable Disease: VDL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Janssen-Cilag International NV: lead

Study Sites (42)

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Bordeaux, France

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Le Mans, France

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Lille, France

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Tours, France

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Duisburg, Germany

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Essen, Germany

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Frankfurt (Oder), Germany

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Leipzig, Germany

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München, Germany

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Mÿnchen, Germany

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Oldenburg, Germany

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Ulm, Germany

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Athens, Greece

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Pátrai, Greece

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Budapest, Hungary

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Debrecen, Hungary

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Miskolc, Hungary

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Nyíregyháza, Hungary

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Szeged, Hungary

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Kaunas, Lithuania

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Klaipėda, Lithuania

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Vilnius Lt, Lithuania

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Bialystok, Poland

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Katowice, Poland

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Krakow, Poland

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Lodz, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Belgrade, Serbia

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Kamenitz, Serbia

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Niš, Serbia

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Novi Sad, Serbia

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Barcelona, Spain

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Madrid, Spain

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Toledo, Spain

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Valencia, Spain

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Ankara, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

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Bath, United Kingdom

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Edinburgh, United Kingdom

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London, United Kingdom

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Related Publications (1)

• 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.

  PMID: 25261096 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Bone Marrow Neoplasms; Disease Progression

Interventions

Cyclophosphamide; Bortezomib; Dexamethasone; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Hematologic Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The response rate of bortezomib in combination with dexamethasone after 4 cycles was much higher than originally assumed. Therefore the sample size of the randomized groups is too small for further statistical analysis.

Results Point of Contact

• Title: EMEA Medical Affairs Director Oncology
• Organization: Janssen-Cilag Germany

+49 2137 955-492

Study Officials

• Janssen-Cilag International NV Clinical Trial

  Janssen-Cilag International NV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2009
• First Posted: May 25, 2009
• Study Start: May 1, 2008
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: January 15, 2015
• Results First Posted: June 8, 2012

Record last verified: 2015-01

Locations

DE (8); ES (4); SE (4); HU (5); FR (4); LI (3); PL (6); TU (3); GB (3); GR (2)