Clinical trial NCT00872521: A Study of Efficacy of Treatment With Bortezomib (in Combination With Doxorubicin and Dexamethasone) in Previously Untreated Patients With Multiple Myeloma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
transplant eligible
doxorubicin
dexamethasone
bortezomib
bortezomib resistance
PAD induction
PIMMS Trial
Lead sponsor: Janssen-Cilag Pty Ltd
Sponsor class: INDUSTRY
First posted: 2009-03-31
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: 84 days
Secondary outcomes:
measure: Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction
timeFrame: 84 days
measure: Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT).
timeFrame: 3-months following ASCT
measure: Disease Response 3-months After Autologous Stem Cell Transplant (ASCT)
timeFrame: 3-months after ASCT
measure: Event Free Survival (EFS)
timeFrame: 2 years after Day 1 Cycle 1 of PAD
measure: Overall Survival
timeFrame: 2 years after Day 1 Cycle 1 of PAD
measure: Assessment of Quality of Life (AQoL) Scores
timeFrame: Up to 2 years
measure: Overall Response Rate (ORR) Stratified by Protein Expression (p53)
timeFrame: 84 days
measure: Overall Response Rate (ORR) Stratified by Protein Expression (Cyclin D1).
timeFrame: 84 days
measure: Overall Response Rate (ORR) Stratified by Protein Expression (Bcl-2)
timeFrame: 84 days
measure: Overall Response Rate (ORR) Stratified by Protein Expression (FGFR3)
timeFrame: 84 days
measure: Overall Survival (OS) Stratified by Protein Expression (p53).
timeFrame: 2 years after Day 1 Cycle 1 of PAD
measure: Overall Survival (OS) Stratified by Protein Expression (Cyclin D1)
timeFrame: 2 years after Day 1 Cycle 1 of PAD
measure: Overall Survival (OS) Stratified by Protein Expression (Bcl-2)
timeFrame: 2 years after Day 1 Cycle 1 of PAD
measure: Overall Survival (OS) Stratified by Protein Expression (FGFR3)
timeFrame: 2 years after Day 1 Cycle 1 of PAD
Other outcomes:
Locations:
city: Adelaide
country: Australia
city: Box Hill
country: Australia
city: Brisbane
country: Australia
city: Camperdown
country: Australia
city: Geelong
country: Australia
city: Gosford
country: Australia
city: Greenslopes
country: Australia
city: Malvern
country: Australia
city: Melbourne
country: Australia
city: Parkville
country: Australia
city: Perth
country: Australia
city: Sydney
country: Australia
city: Westmead
country: Australia
city: Woden
country: Australia
city: Wollongong
country: Australia
city: Woolloongabba N/A
country: Australia
Study officials:
affiliation: Janssen-Cilag Pty Ltd
name: Janssen-Cilag Pty Ltd Clinical Trial
role: STUDY_DIRECTOR
References: