A Study of Efficacy of Treatment With Bortezomib (in Combination With Doxorubicin and Dexamethasone) in Previously Untreated Patients With Multiple Myeloma
Information source: Janssen-Cilag Pty Ltd
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Myeloma
Intervention: PAD induction (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Janssen-Cilag Pty Ltd Official(s) and/or principal investigator(s): Janssen-Cilag Pty Ltd Clinical Trial, Study Director, Affiliation: Janssen-Cilag Pty Ltd
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.
Clinical Details
Official title: 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
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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
Secondary outcome: Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) InductionOverall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) Event Free Survival (EFS) Overall Survival Assessment of Quality of Life (AQoL) Scores Overall Response Rate (ORR) Stratified by Protein Expression (p53) Overall Response Rate (ORR) Stratified by Protein Expression (Cyclin D1). Overall Response Rate (ORR) Stratified by Protein Expression (Bcl-2) Overall Response Rate (ORR) Stratified by Protein Expression (FGFR3) Overall Survival (OS) Stratified by Protein Expression (p53). Overall Survival (OS) Stratified by Protein Expression (Cyclin D1) Overall Survival (OS) Stratified by Protein Expression (Bcl-2) Overall Survival (OS) Stratified by Protein Expression (FGFR3)
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).
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Adelaide, Australia
Box Hill, Australia
Brisbane, Australia
Camperdown, Australia
Geelong, Australia
Gosford, Australia
Greenslopes, Australia
Malvern, Australia
Melbourne, Australia
Parkville, Australia
Perth, Australia
Sydney, Australia
Westmead, Australia
Woden, Australia
Wollongong, Australia
Woolloongabba N/A, Australia
Additional Information
Starting date: January 2009
Last updated: May 7, 2014
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