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A Study of Efficacy of Treatment With Bortezomib (in Combination With Doxorubicin and Dexamethasone) in Previously Untreated Patients With Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00872521
Recruitment Status : Completed
First Posted : March 31, 2009
Results First Posted : May 7, 2013
Last Update Posted : May 16, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag Pty Ltd

Tracking Information
First Submitted Date  ICMJE March 27, 2009
First Posted Date  ICMJE March 31, 2009
Results First Submitted Date  ICMJE December 14, 2012
Results First Posted Date  ICMJE May 7, 2013
Last Update Posted Date May 16, 2014
Study Start Date  ICMJE January 2009
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2013)
Overall Response Rate (ORR): Number of Participants Who Are Responders (Had Stringent Complete Response [sCR], CR, Very Good Partial Response [VGPR] or Partial Response [PR]) After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction [ Time Frame: 84 days ]
International Myeloma Working Group (IMWG) criteria - CR: negative immunofixation on the serum and urine, no soft tissue plasmacytomas and <5% plasma cells in the bone marrow; sCR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR: serum and urine M-protein detected by immunofixation but not electrophoresis, >90% in serum M-protein+urine, M-protein level <100 mg/24hour; PR: ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or <200 mg/24hour
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2009)
The primary objective is to compare the overall response rate following 4 cycles of PAD induction therapy between patients with and without amplification of 1q21 (measured by FISH) in their marrow at baseline.
Change History Complete list of historical versions of study NCT00872521 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2013)
  • Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction [ Time Frame: 84 days ]
    Number of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) and stable disease (SD).
  • Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). [ Time Frame: 3-months following ASCT ]
    Responders are the number of participants who achieved stringent complete response (sCR)/ complete response (CR), very good partial response (VGPR) or partial response (PR) following PAD induction.
  • Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) [ Time Frame: 3-months after ASCT ]
    Number of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) and relapse as per IMWG criteria.
  • Event Free Survival (EFS) [ Time Frame: 2 years after Day 1 Cycle 1 of PAD ]
    Percentage of participants who did not have any of the following events: Death, Disease progression, Relapse, Cardiovascular accidents, Deep vein thrombosis, Pulmonary embolism, Fracture, Acute renal failure, Nervous system disorders 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD).
  • Overall Survival [ Time Frame: 2 years after Day 1 Cycle 1 of PAD ]
    Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD).
  • Assessment of Quality of Life (AQoL) Scores [ Time Frame: Up to 2 years ]
    The AQoL is a multi-attribute utility health-related quality of life (HRQoL) instrument. It combines the 4 dimensions of independent living, relationships, senses and mental health into a single utility score. The AQoL instrument scores between 1 (best HRQoL) and -0.04 (worst possible HRQoL).
  • Overall Response Rate (ORR) Stratified by Protein Expression (p53) [ Time Frame: 84 days ]
    Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (p53).
  • Overall Response Rate (ORR) Stratified by Protein Expression (Cyclin D1). [ Time Frame: 84 days ]
    Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (Cyclin D1).
  • Overall Response Rate (ORR) Stratified by Protein Expression (Bcl-2) [ Time Frame: 84 days ]
    Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (bcl-2)
  • Overall Response Rate (ORR) Stratified by Protein Expression (FGFR3) [ Time Frame: 84 days ]
    Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (FGFR3)
  • Overall Survival (OS) Stratified by Protein Expression (p53). [ Time Frame: 2 years after Day 1 Cycle 1 of PAD ]
    Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD) stratified by protein expression (p53).
  • Overall Survival (OS) Stratified by Protein Expression (Cyclin D1) [ Time Frame: 2 years after Day 1 Cycle 1 of PAD ]
    Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD) stratified by protein expression (Cyclin D1).
  • Overall Survival (OS) Stratified by Protein Expression (Bcl-2) [ Time Frame: 2 years after Day 1 Cycle 1 of PAD ]
    Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD) stratified by protein expression (bcl-2).
  • Overall Survival (OS) Stratified by Protein Expression (FGFR3) [ Time Frame: 2 years after Day 1 Cycle 1 of PAD ]
    Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD) stratified by protein expression (FGFR3).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2009)
To compare the overall response rate to PAD induction therapy 3-months following ASCT. To determine the event-free survival and overall survival at 2 years after Day 1 Cycle 1 of PAD.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Efficacy of Treatment With Bortezomib (in Combination With Doxorubicin and Dexamethasone) in Previously Untreated Patients With Multiple Myeloma
Official Title  ICMJE A Phase II Trial of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction Therapy in Patients With Untreated Multiple Myeloma (MM), Stratified for Markers of Bortezomib Resistance
Brief Summary The purpose of this study is to determine efficacy of treatment with bortezomib (in combination with doxorubicin and dexamethasone) in previously untreated patients with Multiple Myeloma.
Detailed Description This is an open-label, single-arm, multicentre study which will enroll approximately 105 patients. Open-label means all people involved in the study know the identity of the intervention. Single-arm means there is one group of patients, all receiving the same treatment. Four 21-day cycles of a combination of bortezomib i.v. (intravenous) 1.3 mg/m2 (Days 1, 4, 8 and 11), doxorubicin i.v. 20 mg/m2 (days 1 and 4) and dexamethasone p.o. (by mouth) (days 1, 2, 4, 5, 8, 9, 11 and 12) (PAD) will be given. Patients will be discontinued if disease progresses, or unacceptable treatment-related toxicity occurs. Following PAD treatment, patients will have peripheral blood stem cells (PBSC) collected, and an autologous stem cell transplant (ASCT) will be performed. Patients will then make monthly visits to the Study Doctor until 1 year after start of treatment, and attend a final follow-up visit at 2 years. Efficacy assessment of response to PAD will be made using the International Myeloma Working Group (IMWG) criteria. The primary outcome is to compare the overall response rate following 4 cycles of PAD induction therapy between patients with and without extra copies of the long arm of the first chromosome (1q21) measured by fluorescent in situ hybridisation (FISH) in their marrow at baseline. Patient reported outcomes will be assessed using the AQoL (Assessment of Quality of Life). Safety will be evaluated throughout the study by assessment of adverse events including changes in physical examination, concomitant medication, ECOG (Eastern Cooperative Oncology Group) scores, vital signs and clinical laboratory findings. A sample size of 105 provides 80% power (a=0.05) to detect a difference in overall response rate of 28% at the end of 4 cycles of PAD. This is based on the assumptions that 44% of patients have amplification of 1q21 1, 2, the overall response rate with PAD combination therapy is 80%; the overall response rate with PAD if PAD therapy does not overcome 1q21 amplification is assumed to be 64%, while without 1q21 amplification it is assumed to be 92%. That is: Overall Response Rate (ORR) = P1q21 amplified x ORRamplified + P1q21 not amplified x ORRnot amplified i.e. 80% = 44% x 64% + 56% x 92%. The sample size of 105 allows for a 20% drop-out rate. Four 21-day cycles of PAD: a combination of bortezomib i.v. (intravenous) 1.3 mg/m2 (Days 1, 4, 8 and 11), doxorubicin i.v. 20 mg/m2 (days 1 and 4) and dexamethasone p.o. (by mouth) (days 1, 2, 4, 5, 8, 9, 11 and 12).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Drug: PAD induction

Open Label Treatment:

Four 21-day Treatment Cycles Bortezomib 1.3 mg/m2 i.v. (D1, 4, 8 & 11), Doxorubicin 20 mg/m2 i.v. (D1 & 4), Dexamethasone 20 mg p.o. (D1, 2, 4, 5, 8 , 9, 11 & 12)

Study Arms  ICMJE Experimental: bortezomib; doxorubicin; dexamethasone
PAD induction Open Label Treatment: Four 21-day Treatment Cycles Bortezomib 1.3 mg/m2 i.v. (D1 4 8 & 11) Doxorubicin 20 mg/m2 i.v. (D1 & 4) Dexamethasone 20 mg p.o. (D1 2 4 5 8 9 11 & 12)
Intervention: Drug: PAD induction
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 16, 2012)
107
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2009)
105
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Previously diagnosed with multiple myeloma
  • eligible for autologous stem cell transplantation
  • meets pre-treatment lab criteria (as defined within protocol).

Exclusion Criteria:

  • Previously received treatment for multiple myeloma (including prior therapy with radiation or pulsed dexamethasone), except localised radiation to a solitary lesion or plasmacytomas or 4 days of corticosteroid therapy
  • have a current diagnosis of smoldering multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), or Waldenström Macroglobulinemia
  • have a history of any other malignancy within 5 years before enrolment
  • have other significant comorbidities.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00872521
Other Study ID Numbers  ICMJE CR015640
26866138MMY2059 ( Other Identifier: Janssen-Cilag Pty Ltd, Australia )
PIMMS Trial ( Other Identifier: Janssen-Cilag Pty Ltd, Australia )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen-Cilag Pty Ltd
Study Sponsor  ICMJE Janssen-Cilag Pty Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen-Cilag Pty Ltd Clinical Trial Janssen-Cilag Pty Ltd
PRS Account Janssen-Cilag Pty Ltd
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP