Trial Outcomes & Findings for Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide for Relapsed/Refractory Multiple Myeloma (NCT NCT01160484)

Last Updated: 2015-05-04

Results Overview

The investigator will evaluate each patient for response to therapy according to criteria augmented from those developed by Bladé et al., 1998 presented below (Table 7-1). Assessment of disease response will be performed prior to drug administration on Day 1 of Cycles 2 8 and at the End of Study Treatment visit. If a patient is determined to have complete response (CR), very good partial response (VGPR), partial response (PR), or minor response (MR), then assessment of disease response is to be performed 4 weeks later to confirm the response.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Up to 7.5 months (eight 28-day cycles)

Results posted on

2015-05-04

Participant Flow

This study enrolled patients from eight different clinical sites sites in the United States. Data was collected from September 2009 until July 25, 2011

Participant milestones

Participant milestones
Measure	DVD-R Single Arm Dose schematic of Dexamethasone + Bortezomib + Pegylated Liposomal Doxorubicin (PLD)+ Lenalidomide (DVD-R) Therapy: Per 28 Day Cycle, patients will received drug in the following order, dosing and schedule: 1\) Dexamethasone- 40 mg intravenous infusion (IV) on Days 1, 4, 8 and 11; 2) Bortezomib- 1.0 mg/m2 infused over 3 to 5 seconds followed by a standard saline flush on Days 1, 4, 8 and 11; 3) Pegylated Liposomal Doxorubicin- 4.0 mg/m2 IV as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle; and 4) Lenalidomide- 10 mg PO on days 1-14
Overall Study STARTED	40
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Reasons for withdrawal
Measure	DVD-R Single Arm Dose schematic of Dexamethasone + Bortezomib + Pegylated Liposomal Doxorubicin (PLD)+ Lenalidomide (DVD-R) Therapy: Per 28 Day Cycle, patients will received drug in the following order, dosing and schedule: 1\) Dexamethasone- 40 mg intravenous infusion (IV) on Days 1, 4, 8 and 11; 2) Bortezomib- 1.0 mg/m2 infused over 3 to 5 seconds followed by a standard saline flush on Days 1, 4, 8 and 11; 3) Pegylated Liposomal Doxorubicin- 4.0 mg/m2 IV as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle; and 4) Lenalidomide- 10 mg PO on days 1-14
Overall Study Lack of Efficacy	9
Overall Study Adverse Event	6
Overall Study Withdrawal by Subject	2
Overall Study inclusion/exclusion criteria failure	1

Baseline Characteristics

Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide for Relapsed/Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DVD-R Single Arm n=40 Participants Dose schematic of Dexamethasone + Bortezomib + Pegylated Liposomal Doxorubicin + Lenalidomide (DVD-R) Therapy: Per 28 Day Cycle, patients will received drug in the following order, dosing and schedule: 1\) Dexamethasone- 40 mg intravenous infusion (IV) on Days 1, 4, 8 and 11; 2) Bortezomib- 1.0 mg/m2 infused over 3 to 5 seconds followed by a standard saline flush on Days 1, 4, 8 and 11; 3) Pegylated Liposomal Doxorubicin- 4.0 mg/m2 IV as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle; and 4) Lenalidomide- 10 mg PO on days 1-14
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants
Age, Categorical >=65 years	27 Participants n=5 Participants
Age, Continuous	71 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
International Staging System (ISS); stage (N) I (beta 2 microglobulin(B2M )<3.5 +Albumin ≥3.5)	16 participants n=5 Participants
International Staging System (ISS); stage (N) II (B2M 3.5 +albumin < 3.5; or B2M 3.5-5.5)	14 participants n=5 Participants
International Staging System (ISS); stage (N) III (B2M >5.5)	10 participants n=5 Participants
Serum M-protein	2.05 g/dL n=5 Participants
Urine-M protein	261.1 mg/dL n=5 Participants
Serum creatinine	1.0 mg/dL n=5 Participants
Prior treatments	3 number of treatments n=5 Participants
Total Number of prior lines of treatment Bortezomib (BTZ)	33 number of treatments n=5 Participants
Total Number of prior lines of treatment Alkylating agents	20 number of treatments n=5 Participants
Total Number of prior lines of treatment PLD or Doxorubucin	15 number of treatments n=5 Participants
Total Number of prior lines of treatment Thalidomide	15 number of treatments n=5 Participants
Total Number of prior lines of treatment Lenalidomide (LEN)	19 number of treatments n=5 Participants
Total Number of prior lines of treatment Glucocorticoids	35 number of treatments n=5 Participants
Total Number of prior lines of treatment HDAC inhibitors (panobinostat/romidepsin)	7 number of treatments n=5 Participants
Total Number of prior lines of treatment Transplant (autologous)	5 number of treatments n=5 Participants
Total Number of prior lines of treatment Other	11 number of treatments n=5 Participants
Total Number of prior lines of treatment PLD+btz+dexamethasone (dex)	17 number of treatments n=5 Participants
Total Number of prior lines of treatment PLD+btz+dex and len+ glucocorticoids	10 number of treatments n=5 Participants

PRIMARY outcome

Timeframe: Up to 7.5 months (eight 28-day cycles)

Population: Population analysis was carried out as per protocol. Efficacy was evaluated via a modified version of the Bladé response criteria \[complete response (CR), very good partial response (VGPR), partial response (PR), and those achieving minimal response (MR)\]

Outcome measures

Outcome measures
Measure	DVD-R Single Arm n=39 Participants 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
International Myeloma Working Group (IMWG) Response Criteria CR	8 participants
International Myeloma Working Group (IMWG) Response Criteria VGPR	4 participants
International Myeloma Working Group (IMWG) Response Criteria PR	7 participants
International Myeloma Working Group (IMWG) Response Criteria Objective Response (CR+VGPR+PR)	19 participants
International Myeloma Working Group (IMWG) Response Criteria MR	14 participants
International Myeloma Working Group (IMWG) Response Criteria Clinical Benefit (CR+VGPR+PR+MR)	33 participants
International Myeloma Working Group (IMWG) Response Criteria Estable disease	4 participants
International Myeloma Working Group (IMWG) Response Criteria Progressive disease	2 participants

SECONDARY outcome

Timeframe: Up to 7.5 months (eight 28-day cycles)

Outcome measures

Outcome measures
Measure	DVD-R Single Arm n=33 Participants 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
Time to First Response	1 months Interval 1.0 to 5.0

SECONDARY outcome

Timeframe: Up to 7.5 months (eight 28-day cycles)

Outcome measures

Outcome measures
Measure	DVD-R Single Arm n=33 Participants 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
Time to Best Response	2 months Interval 1.0 to 6.0

SECONDARY outcome

Timeframe: First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death.

Outcome measures

Outcome measures
Measure	DVD-R Single Arm n=33 Participants 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
Duration of Response	12 months Interval 1.0 to 21.0

SECONDARY outcome

Timeframe: Time from the start of treatment to progressive disease

Outcome measures

Outcome measures
Measure	DVD-R Single Arm n=39 Participants 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
Time to Progression	9 months Interval 1.0 to 22.0

SECONDARY outcome

Timeframe: Time from the start of treatment to progressive disease or until death

Outcome measures

Outcome measures
Measure	DVD-R Single Arm n=39 Participants 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
Progression-free Survival	9 months Interval 1.0 to 22.0

SECONDARY outcome

Timeframe: Follow-up visits for disease progression and overall survival every 3 months after study discontinuation. After progression, follow-up visits for survival status every 6 months or until alternate therapy needs to be started or death intervenes

time that patients were monitored for disease progression and overall survival

Outcome measures

Outcome measures
Measure	DVD-R Single Arm n=39 Participants 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
Follow-up Time	11 months Interval 2.0 to 22.0

Adverse Events

DVD-R Single Arm

Serious events: 10 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DVD-R Single Arm n=40 participants at risk 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
Respiratory, thoracic and mediastinal disorders Pneumonia	12.5% 5/40 • Number of events 5 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
General disorders Abdominal pain	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Gastrointestinal disorders Vomiting	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Skin and subcutaneous tissue disorders Cellulitis	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Gastrointestinal disorders Disphagia	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Immune system disorders Allergic reaction	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
General disorders Loss of balance	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary emboli	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Vascular disorders Septic thrombophlebitis	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Nervous system disorders Syncopal episode	2.5% 1/40 • Number of events 1 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.

Other adverse events

Other adverse events
Measure	DVD-R Single Arm n=40 participants at risk 40 mg dexamethasone will be administered IV on Days 1, 4, 8, and 11 of each cycle. 1.0 mg/m2 Bortezomib will be administered IV over 3 to 5 seconds followed by a standard saline flush, on Days 1, 4, 8, and 11 immediately following the dexamethasone infusion. 4.0 mg/m2 PLD will be given as a 90 minute infusion on Day 1 of Cycle 1 and subsequent doses may be administered over 30 to 60 minutes on Days 4, 8 and 11 of Cycle 1 and on Days 1, 4, 8, and 11 of each subsequent cycle, following the bortezomib administration. 10 mg/day lenalidomide will be administered PO on days 1-14 of a 28-day treatment cycle, followed by a 14-day rest period, following the PLD administration.
General disorders Fatigue	40.0% 16/40 • Number of events 16 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Blood and lymphatic system disorders Neutropenia	35.0% 14/40 • Number of events 14 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Blood and lymphatic system disorders Thrombocytopenia	35.0% 14/40 • Number of events 14 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Blood and lymphatic system disorders Anemia	30.0% 12/40 • Number of events 12 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Blood and lymphatic system disorders Edema	30.0% 12/40 • Number of events 12 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	30.0% 12/40 • Number of events 12 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Nervous system disorders Periphenal neurophaty	25.0% 10/40 • Number of events 10 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Gastrointestinal disorders Diarrhea	25.0% 10/40 • Number of events 10 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Gastrointestinal disorders Nausea	25.0% 10/40 • Number of events 10 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Psychiatric disorders Confusion	22.5% 9/40 • Number of events 9 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Metabolism and nutrition disorders Hypocalcemia	20.0% 8/40 • Number of events 8 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Blood and lymphatic system disorders Leukopenia	17.5% 7/40 • Number of events 7 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Reproductive system and breast disorders Pelvic pain	17.5% 7/40 • Number of events 7 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	15.0% 6/40 • Number of events 6 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Metabolism and nutrition disorders Hypokalemia	15.0% 6/40 • Number of events 6 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonia	15.0% 6/40 • Number of events 6 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
Gastrointestinal disorders Abdominal pain	12.5% 5/40 • Number of events 5 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.
General disorders Generalized pain	12.5% 5/40 • Number of events 5 • Severity and frequency of adverse events (AEs) were evaluated at each visit. Serious adverse events (SAEs) were followed until resolution or until clearly determined be unrelated to study treatment.

Additional Information

Director, Clinical Operations

Oncotherapeutics

Phone: 323-623-1200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place