Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, transplant eligible, doxorubicin, dexamethasone, bortezomib, bortezomib resistance, PAD induction, PIMMS Trial
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).
Interventions
DRUGPAD 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)
Sponsors
Janssen-Cilag Pty Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | 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). | 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) | 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) | 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 | 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 | 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) | 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). | 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) | 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) | 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). | 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) | 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) | 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) | 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). |
Countries
Australia
Participant flow
Recruitment details
The participants were enrolled at multiple sites in Australia
Pre-assignment details
107 participants were enrolled and they all received the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| 1q21 Amplified Participants with 1q21 amplification. Four 21-day cycles of bortezomib 1.3 mg/m2 intravenous (IV) on Days 1, 4, 8 and 11; plus doxorubicin 20 mg/m2 IV on Days 1 and 4; and dexamethasone 20 mg oral on Days 1, 2, 4, 5, 8, 9, 11 and 12. | 26 |
| 1q21 Not Amplified Participants without 1q21 amplification. Four 21-day cycles of bortezomib 1.3 mg/m2 intravenous (IV) on Days 1, 4, 8 and 11; plus doxorubicin 20 mg/m2 IV on Days 1 and 4; and dexamethasone 20 mg oral on Days 1, 2, 4, 5, 8, 9, 11 and 12. | 72 |
| Failed/Missing Test Participants who failed 1q21 test/had missing results for 1q21 test. Four 21-day cycles of bortezomib 1.3 mg/m2 intravenous (IV) on Days 1, 4, 8 and 11; plus doxorubicin 20 mg/m2 IV on Days 1 and 4; and dexamethasone 20 mg oral on Days 1, 2, 4, 5, 8, 9, 11 and 12. | 9 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Completed 3-month Follow up | Other | 0 | 2 | 0 |
| Completed 3-month Follow up | Physician Decision | 0 | 1 | 0 |
| Completed PAD Induction | Adverse Event | 4 | 0 | 0 |
| Completed PAD Induction | Death | 1 | 1 | 0 |
| Completed PAD Induction | Disease progression | 0 | 2 | 0 |
| Completed PAD Induction | Patient choice | 0 | 1 | 0 |
| Primary Endpoint Analysis | Efficacy data unavailable | 0 | 2 | 0 |
| Primary Endpoint Analysis | Other | 1 | 2 | 0 |
| Primary Endpoint Analysis | Patient choice | 0 | 1 | 0 |
| Primary Endpoint Analysis | Patient response missing | 0 | 0 | 1 |
| Secondary Endpoint Analysis | Efficacy data unavailable | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | 1q21 Amplified | 1q21 Not Amplified | Failed/Missing Test | Total |
|---|---|---|---|---|
| Age, Continuous | 58.0 Years STANDARD_DEVIATION 7.6 | 58.1 Years STANDARD_DEVIATION 10.1 | 55.6 Years STANDARD_DEVIATION 8.1 | 57.9 Years STANDARD_DEVIATION 9.3 |
| Race/Ethnicity, Customized Appears White | 1 Participants | 4 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Indian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Mauritian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Middle Eastern | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Missing race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized South American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 23 Participants | 63 Participants | 8 Participants | 94 Participants |
| Sex: Female, Male Female | 9 Participants | 26 Participants | 4 Participants | 39 Participants |
| Sex: Female, Male Male | 17 Participants | 46 Participants | 5 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 26 | 72 / 72 | 9 / 9 | 107 / 107 |
| serious Total, serious adverse events | 15 / 26 | 30 / 72 | 5 / 9 | 50 / 107 |
Outcome results
Primary
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
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
Time frame: 84 days
Population: Intent-to-treat (ITT) population- All enrolled participants who proceeded to receive Day 1 of Cycle 1 of PAD induction.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1q21 Not Amplified | 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 | Non Responder | 8 Participants |
| 1q21 Not Amplified | 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 | Total | 63 Participants |
| 1q21 Not Amplified | 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 | Responder | 55 Participants |
| 1q21 Amplified | 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 | Non Responder | 0 Participants |
| 1q21 Amplified | 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 | Total | 20 Participants |
| 1q21 Amplified | 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 | Responder | 20 Participants |
| Failed/Missing Test | 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 | Responder | 7 Participants |
| Failed/Missing Test | 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 | Non Responder | 1 Participants |
| Failed/Missing Test | 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 | Total | 8 Participants |
| Total | 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 | Non Responder | 9 Participants |
| Total | 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 | Total | 91 Participants |
| Total | 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 | Responder | 82 Participants |
Comparison: Null Hypothesis: There is no difference in response rate between 1q21 amplified and 1q21 NOT amplifiedp-value: 0.09Chi-squared
Secondary
Assessment of Quality of Life (AQoL) Scores
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).
Time frame: Up to 2 years
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1q21 Not Amplified | Assessment of Quality of Life (AQoL) Scores | 0.0516596 Scores on a scale | Standard Deviation 0.2769184 |
| 1q21 Amplified | Assessment of Quality of Life (AQoL) Scores | 0.0068695 Scores on a scale | Standard Deviation 0.3366162 |
| Failed/Missing Test | Assessment of Quality of Life (AQoL) Scores | 0.1267145 Scores on a scale | Standard Deviation 0.1839149 |
| Total | Assessment of Quality of Life (AQoL) Scores | 0.0480281 Scores on a scale | Standard Deviation 0.2844673 |
Secondary
Disease Response 3-months After Autologous Stem Cell Transplant (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.
Time frame: 3-months after ASCT
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1q21 Not Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | stringent complete response (sCR) | 6 Participants |
| 1q21 Not Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Relapse | 1 Participants |
| 1q21 Not Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Stable Disease (SD) | 3 Participants |
| 1q21 Not Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | complete response (CR) | 8 Participants |
| 1q21 Not Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Total | 58 Participants |
| 1q21 Not Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Very Good Partial Response (VGPR) | 21 Participants |
| 1q21 Not Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Partial Response (PR) | 19 Participants |
| 1q21 Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Relapse | 0 Participants |
| 1q21 Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Partial Response (PR) | 5 Participants |
| 1q21 Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Very Good Partial Response (VGPR) | 7 Participants |
| 1q21 Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Stable Disease (SD) | 0 Participants |
| 1q21 Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Total | 20 Participants |
| 1q21 Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | complete response (CR) | 3 Participants |
| 1q21 Amplified | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | stringent complete response (sCR) | 5 Participants |
| Failed/Missing Test | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Partial Response (PR) | 3 Participants |
| Failed/Missing Test | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | stringent complete response (sCR) | 3 Participants |
| Failed/Missing Test | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | complete response (CR) | 0 Participants |
| Failed/Missing Test | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Very Good Partial Response (VGPR) | 1 Participants |
| Failed/Missing Test | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Stable Disease (SD) | 0 Participants |
| Failed/Missing Test | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Relapse | 0 Participants |
| Failed/Missing Test | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Total | 7 Participants |
| Total | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Very Good Partial Response (VGPR) | 29 Participants |
| Total | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Total | 85 Participants |
| Total | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Relapse | 1 Participants |
| Total | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | complete response (CR) | 11 Participants |
| Total | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | stringent complete response (sCR) | 14 Participants |
| Total | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Stable Disease (SD) | 3 Participants |
| Total | Disease Response 3-months After Autologous Stem Cell Transplant (ASCT) | Partial Response (PR) | 27 Participants |
Comparison: Null Hypothesis: There is no difference in response rate between 1q21 amplified and 1q21 NOT amplifiedp-value: 0.56Chi-squared
Secondary
Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction
Number of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) and stable disease (SD).
Time frame: 84 days
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1q21 Not Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | stringent complete response (sCR) | 5 Particiipants |
| 1q21 Not Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | complete response (CR) | 6 Particiipants |
| 1q21 Not Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Very Good Partial Response (VGPR) | 15 Particiipants |
| 1q21 Not Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Partial Response (PR) | 29 Particiipants |
| 1q21 Not Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Stable Disease (SD) | 8 Particiipants |
| 1q21 Not Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Total | 63 Particiipants |
| 1q21 Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Total | 20 Particiipants |
| 1q21 Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Partial Response (PR) | 11 Particiipants |
| 1q21 Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | stringent complete response (sCR) | 3 Particiipants |
| 1q21 Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Very Good Partial Response (VGPR) | 3 Particiipants |
| 1q21 Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | complete response (CR) | 3 Particiipants |
| 1q21 Amplified | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Stable Disease (SD) | 0 Particiipants |
| Failed/Missing Test | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | complete response (CR) | 0 Particiipants |
| Failed/Missing Test | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Very Good Partial Response (VGPR) | 3 Particiipants |
| Failed/Missing Test | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Partial Response (PR) | 3 Particiipants |
| Failed/Missing Test | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Total | 8 Particiipants |
| Failed/Missing Test | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Stable Disease (SD) | 1 Particiipants |
| Failed/Missing Test | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | stringent complete response (sCR) | 1 Particiipants |
| Total | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Stable Disease (SD) | 9 Particiipants |
| Total | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Total | 91 Particiipants |
| Total | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | complete response (CR) | 9 Particiipants |
| Total | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Partial Response (PR) | 43 Particiipants |
| Total | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | stringent complete response (sCR) | 9 Particiipants |
| Total | Disease Response After 4 Cycles of Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction | Very Good Partial Response (VGPR) | 21 Particiipants |
Comparison: Null Hypothesis: There is no difference in response rate between 1q21 amplified and 1q21 NOT amplifiedp-value: 0.23Chi-squared
Secondary
Event Free Survival (EFS)
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).
Time frame: 2 years after Day 1 Cycle 1 of PAD
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1q21 Not Amplified | Event Free Survival (EFS) | 75.0 Percentage of participants |
| 1q21 Amplified | Event Free Survival (EFS) | 69.6 Percentage of participants |
Comparison: Null Hypothesis: There is no difference in response rate between 1q21 amplified and 1q21 NOT amplifiedp-value: 0.01Log Rank
Secondary
Overall Response Rate (ORR) Stratified by Protein Expression (Bcl-2)
Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (bcl-2)
Time frame: 84 days
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The ORR was imputed, with those who discontinued treatment or who had efficacy data unavailable being coded as Non-Responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1q21 Not Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (Bcl-2) | bcl-2 Non Responder | 2 Participants |
| 1q21 Not Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (Bcl-2) | bcl-2 Responder | 10 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (Bcl-2) | bcl-2 Non Responder | 15 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (Bcl-2) | bcl-2 Responder | 62 Participants |
Secondary
Overall Response Rate (ORR) Stratified by Protein Expression (Cyclin D1).
Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (Cyclin D1).
Time frame: 84 days
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The ORR was imputed, with those who discontinued treatment or who had efficacy data unavailable being coded as Non-Responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1q21 Not Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (Cyclin D1). | Cyclin D1 Non Responder | 11 Participants |
| 1q21 Not Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (Cyclin D1). | Cyclin D1 Responder | 48 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (Cyclin D1). | Cyclin D1 Non Responder | 5 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (Cyclin D1). | Cyclin D1 Responder | 20 Participants |
Secondary
Overall Response Rate (ORR) Stratified by Protein Expression (FGFR3)
Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (FGFR3)
Time frame: 84 days
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The ORR was imputed, with those who discontinued treatment or who had efficacy data unavailable being coded as Non-Responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1q21 Not Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (FGFR3) | FGFR3 Non Responder | 14 Participants |
| 1q21 Not Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (FGFR3) | FGFR3 Responder | 64 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (FGFR3) | FGFR3 Non Responder | 2 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (FGFR3) | FGFR3 Responder | 8 Participants |
Secondary
Overall Response Rate (ORR) Stratified by Protein Expression (p53)
Number of participants who are responders and nonresponders after 4 cycles of bortezomib, doxorubicin and dexamethasone (PAD) induction stratified by protein expression (p53).
Time frame: 84 days
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The ORR was imputed, with those who discontinued treatment or who had efficacy data unavailable being coded as Non-Responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1q21 Not Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (p53) | p53 Non Responder | 14 Participants |
| 1q21 Not Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (p53) | p53 Responder | 61 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (p53) | p53 Non Responder | 3 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) Stratified by Protein Expression (p53) | p53 Responder | 11 Participants |
Secondary
Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (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.
Time frame: 3-months following ASCT
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1q21 Not Amplified | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Non Responder | 4 Participants |
| 1q21 Not Amplified | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Total | 58 Participants |
| 1q21 Not Amplified | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Responder | 54 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Non Responder | 0 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Total | 20 Participants |
| 1q21 Amplified | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Responder | 20 Participants |
| Failed/Missing Test | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Responder | 7 Participants |
| Failed/Missing Test | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Non Responder | 0 Participants |
| Failed/Missing Test | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Total | 7 Participants |
| Total | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Non Responder | 4 Participants |
| Total | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Total | 85 Participants |
| Total | Overall Response Rate (ORR) to Bortezomib, Doxorubicin and Dexamethasone (PAD) Induction 3-months Following Autologous Stem Cell Transplant (ASCT). | Responder | 81 Participants |
Comparison: Null Hypothesis: There is no difference in response rate between 1q21 amplified and 1q21 NOT amplifiedp-value: 0.23Chi-squared
Secondary
Overall Survival
Percentage of participants who had no event of death 2 years after Day 1 Cycle 1 of bortezomib, doxorubicin and dexamethasone (PAD).
Time frame: 2 years after Day 1 Cycle 1 of PAD
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1q21 Not Amplified | Overall Survival | 93.8 Percentage of participants |
| 1q21 Amplified | Overall Survival | 86.4 Percentage of participants |
Comparison: Null Hypothesis: There is no difference in response rate between 1q21 amplified and 1q21 NOT amplifiedp-value: 0.28Log Rank
Secondary
Overall Survival (OS) Stratified by Protein Expression (Bcl-2)
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).
Time frame: 2 years after Day 1 Cycle 1 of PAD
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The OS was not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1q21 Not Amplified | Overall Survival (OS) Stratified by Protein Expression (Bcl-2) | 91.7 Percentage of participants |
| 1q21 Amplified | Overall Survival (OS) Stratified by Protein Expression (Bcl-2) | 90.9 Percentage of participants |
Secondary
Overall Survival (OS) Stratified by Protein Expression (Cyclin D1)
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).
Time frame: 2 years after Day 1 Cycle 1 of PAD
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The OS was not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1q21 Not Amplified | Overall Survival (OS) Stratified by Protein Expression (Cyclin D1) | 89.8 Percentage of participants |
| 1q21 Amplified | Overall Survival (OS) Stratified by Protein Expression (Cyclin D1) | 95.8 Percentage of participants |
Secondary
Overall Survival (OS) Stratified by Protein Expression (FGFR3)
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).
Time frame: 2 years after Day 1 Cycle 1 of PAD
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The OS was not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1q21 Not Amplified | Overall Survival (OS) Stratified by Protein Expression (FGFR3) | 92.5 Percentage of participants |
| 1q21 Amplified | Overall Survival (OS) Stratified by Protein Expression (FGFR3) | 81.8 Percentage of participants |
Secondary
Overall Survival (OS) Stratified by Protein Expression (p53).
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).
Time frame: 2 years after Day 1 Cycle 1 of PAD
Population: Intent-to-treat (ITT) population - All participants who were screened and received at least one dose of PAD. The OS was not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1q21 Not Amplified | Overall Survival (OS) Stratified by Protein Expression (p53). | 90.7 Percentage of participants |
| 1q21 Amplified | Overall Survival (OS) Stratified by Protein Expression (p53). | 92.3 Percentage of participants |