Velcade (Bortezomib), Adriamycin Dexamethasone (PAD) or Vincristine Adriamycin Dexamethasone in Second Line Treatment of Multiple Myeloma

NCT00441168 | Terminated Phase 2 Results

• 3 other identifiers: CR01106526866138MMY20382006-001709-27
• Study Type: interventional
• Target: 30
• Locations: 7 countries
• Sites: 16

Brief Summary

The purpose of this research study is to test the safety and effectiveness of replacing vincristine with a drug called bortezomib (also known as "Velcade"or PS341) in the standard therapy vincristine, doxorubicin (not limited to, but formerly referred to under the tradename Adriamycin) and dexamethasone (VAD) in patients with multiple myeloma. Multiple Myeloma is the second most common cancer of the blood. Bortezomib is the first approved cancer treatment in a new class of medicines called proteasome inhibitors. It disrupts the cell cycle of the cell, affecting numerous biologic pathways, including those related to growth and survival of cancer cells. The treatment will be used as second line treatment, which means either the disease has returned after a period of improvement (relapse) or the disease did not respond to the initial treatment (refractory). Patients will receive either bortezomib (PS341), doxorubicin (Adriamycin) and dexamethasone (PAD) or the VAD standard therapy.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; bortezomib; Cancer; Hematology; bone marrow; immunoglobulin; relapse; refractory; plasma cell; Velcade; adriamycin; dexamethasone; vincristine

Outcome Measures

Primary Outcomes (2)

• Best Confirmed Disease Response

  The primary efficacy analysis was based on the best response obtained during the treatment period according to the European Group for Blood and Marrow Transplantation (EBMT) criteria as assessed by the investigator. The best confirmed response was defined as 2 separate and consecutive evaluations of response, at least 6 weeks apart (for progressive disease \[PD\], 1 to 3 weeks apart). The ordering of the responses was: complete response (CR), partial response (PR), minimal response (MR), no change (NC) and PD. CR was the best response and the poorest response was PD.

  every 28 days during treatment period for up to 6 to 8 cycles

• Best Reported Disease Response

  The primary efficacy analysis was based on the best response obtained during the treatment period according to the EBMT criteria as assessed by the investigator. The ordering of the responses was: CR, PR, MR, NC and PD. CR was the best response and the poorest response was PD.

  every 28 days during treatment period for up to 6 to 8 cycles

Secondary Outcomes (1)

• Duration of Response (DOR)

  every 28 days during treatment period for up to 6 to 8 cycles

Study Arms (2)

VAD Treatment

ACTIVE COMPARATOR

vincristine in combination with adriamycin and dexamethasone

Drug: adriamycin; Drug: dexamethasone; Drug: vincristine

PAD Treatment

EXPERIMENTAL

bortezomib in combination with adriamycin and dexamethasone

Drug: adriamycin; Drug: bortezomib; Drug: dexamethasone

Interventions

adriamycin DRUG

adriamycin: 9mg/m² intravenous (IV) push on days 1 to 4

PAD Treatment; VAD Treatment

bortezomib DRUG

bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11

PAD Treatment

dexamethasone DRUG

dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle

PAD Treatment; VAD Treatment

vincristine DRUG

vincristine: 0.4mg IV push on days 1 to 4

VAD Treatment

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory multiple myeloma following 1 previous line of therapy and, is scheduled by the investigator to be treated with vincristine, adriamycin and dexamethasone standard therapy
• measurable secretory multiple myeloma based on defined criteria
• Karnofsky performance status of \>or = 60%
• fulfils defined laboratory requirements within 14 days before baseline
• if female, the patient is either postmenopausal or surgically sterilised or willing to use an acceptable method of birth control for defined period of time
• if male, the patient agrees to use an acceptable barrier method for contraception for a defined period of time.

You may not qualify if:

• More than one previous line of therapy for multiple myeloma
• use of bortezomib in the previous line of therapy and/or received bortezomib in a previous trial
• known allergy or hypersensitivity to bortezomib, boron or mannitol
• peripheral neuropathy or neuropathic pain of grade 2 or higher
• myocardial infarction within 6 months of enrollment or had 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.

Sponsors & Collaborators

• Janssen-Cilag International NV: lead

Study Sites (16)

Unknown Facility

Zagreb, Croatia

Location

Unknown Facility

Leer, Germany

Location

Unknown Facility

Velbert, Germany

Location

Unknown Facility

Debrecen, Hungary

Location

Unknown Facility

Kaunas, Lithuania

Location

Unknown Facility

Klaipėda, Lithuania

Location

Unknown Facility

Vilnius, Lithuania

Location

Unknown Facility

Bialystok, Poland

Location

Unknown Facility

Gdansk, Poland

Location

Unknown Facility

Poznan, Poland

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Samara, Russia

Location

Unknown Facility

Ankara, Turkey (Türkiye)

Location

Unknown Facility

Bursa, Turkey (Türkiye)

Location

Unknown Facility

Eskişehir, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms; Recurrence

Interventions

Doxorubicin; Bortezomib; Dexamethasone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; 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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Limitations and Caveats

Due to a substantial decline in the use of the VAD regimen as standard of care, recruitment of the study was halted at 30 subjects. It was not possible to statistically evaluate any long term efficacy parameter.

Results Point of Contact

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

rangermu@its.jnj.com

+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: February 27, 2007
• First Posted: February 28, 2007
• Study Start: December 1, 2006
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: March 21, 2014
• Results First Posted: March 21, 2014

Record last verified: 2014-02

Locations

DE (2); LI (3); PL (3); TU (3); RU (3); CR (1); HU (1)