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

This study has been terminated.
(TRIAL STOPPED due to a change in standard of care and the required patient numbers could no longer be achieved)
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT00441168
First received: February 27, 2007
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: adriamycin
Drug: bortezomib
Drug: dexamethasone
Drug: vincristine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Safety and Efficacy of Velcade When Added to Adriamycin-Dexamethasone Treatment Versus Vincristine-Adriamycin-Dexamethasone Standard Treatment in Subjects With Multiple Myeloma Who Are Refractory to or Have Relapsed After Primary Therapy for Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Janssen-Cilag International NV:

Primary Outcome Measures:
  • Best Confirmed Disease Response [ Time Frame: every 28 days during treatment period for up to 6 to 8 cycles ] [ Designated as safety issue: No ]
    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.

  • Best Reported Disease Response [ Time Frame: every 28 days during treatment period for up to 6 to 8 cycles ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Duration of Response (DOR) [ Time Frame: every 28 days during treatment period for up to 6 to 8 cycles ] [ Designated as safety issue: No ]
    DOR was defined as the duration from the date of the best confirmed response for subjects who achieved CR or PR to the date of first documented evidence of PD (or relapse for subjects who experienced CR) over the duration of the study. DOR = ([Date of PD or date of censoring - Date of best response]+1)/30.44.


Enrollment: 30
Study Start Date: December 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: VAD Treatment
vincristine in combination with adriamycin and dexamethasone
Drug: adriamycin
adriamycin: 9mg/m² intravenous (IV) push on days 1 to 4
Drug: dexamethasone
dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle
Drug: vincristine
vincristine: 0.4mg IV push on days 1 to 4
Experimental: PAD Treatment
bortezomib in combination with adriamycin and dexamethasone
Drug: adriamycin
adriamycin: 9mg/m² intravenous (IV) push on days 1 to 4
Drug: bortezomib
bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11
Drug: dexamethasone
dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle

Detailed Description:

Bortezomib, has been approved for use in patients with multiple myeloma, who have already received at least one prior treatment and whose disease is worsening on their last treatment and who have already undergone or are unsuitable for bone marrow transplantation. Bortezomib has significant activity in patients with relapsed multiple myeloma, its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin. The VAD combination has been widely used in multiple myeloma and has demonstrated to be effective in relapsed patients. Based on previous trial results, it is hoped that bortezomib, in replacing vincristine in the VAD standard therapy, can improve the response to treatment of patients with multiple myeloma, with manageable side effects. This is an international, multicentre, randomised, open-label, parallel group study. About 212 patients will take part in the study. Patients will be treated with either bortezomib (PS-341), Adriamycin and Dexamethasone (PAD) or Vincristine, Adriamycin and Dexamethasone (VAD). There will be an initial 14 day screening period to evaluate if the patient is suitable for the study. After screening, eligible patients will be randomised to receive either PAD or VAD. Patients will receive therapy for up to 8 treatment cycles of 28 days each. After the treatment period, there will be a long-term follow-up period with monthly visits until disease progression or relapse. Thereafter follow-up will be continued by at least a phone call every other month. This long-term follow-up period will be performed for all patients until the last patient was treated and followed up for 1 year. Response to treatment will be assessed according to the European group for blood and marrow transplant criteria (EBMT). Disease burden will be monitored by measuring M-protein concentration in serum and in urine every 4 weeks until disease progression or relapse. Thereafter follow-up for survival will be continued every other month by at least a phone call. Safety will be assessed by monitoring of adverse events (AEs), vital signs, physical examination and clinical laboratory tests. Treatment with PAD or VAD will be for up to 8 cycles of 28 days each. Treatment beyond 6 cycles will be discussed on individual basis. Proposed dosages are: bortezomib 1.3 mg/m² intravenous (IV) bolus on Days 1, 4, 8, and 11; vincristine 0.4mg IV push on Days 1 to 4; doxorubicin 9mg/m² IV push on Days 1 to 4; dexamethasone in 1st cycle 40 mg daily on Days 1 to 4, 9 to 12 and 17 to 20, orally (or equivalent parenteral dose) and on subsequent cycles as 40 mg daily on Days 1 to 4 and 17 to 20 only.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00441168

Locations
Croatia
Zagreb, Croatia
Germany
Leer, Germany
Velbert, Germany
Hungary
Debrecen, Hungary
Lithuania
Kaunas, Lithuania
Klaipeda, Lithuania
Vilnius, Lithuania
Poland
Bialystok, Poland
Gdansk, Poland
Poznan, Poland
Russian Federation
Moscow, Russian Federation
Samara, Russian Federation
St Petersburg, Russian Federation
Turkey
Ankara, Turkey
Bursa, Turkey
Eskisehir, Turkey
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Study Director: Janssen-Cilag International NV Clinical Trial Janssen-Cilag International NV
  More Information

No publications provided

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT00441168     History of Changes
Other Study ID Numbers: CR011065, 26866138MMY2038, 2006-001709-27
Study First Received: February 27, 2007
Results First Received: December 3, 2009
Last Updated: February 20, 2014
Health Authority: Belgium: Ministry of Social Affairs, Public Health and the Environment
Germany: Ethics Commission

Keywords provided by Janssen-Cilag International NV:
Multiple Myeloma
bortezomib
Cancer
Hematology
bone marrow
immunoglobulin
relapse
refractory
plasma cell
Velcade
adriamycin
dexamethasone
vincristine

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Liposomal doxorubicin
Bortezomib
Doxorubicin
Vincristine
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 19, 2014