Trial Outcomes & Findings for Pegylated Liposomal Doxorubicin Hydrochloride, Bortezomib, Cyclophosphamide, and Dexamethasone in Treating Patients With Multiple Myeloma (NCT NCT00849251)

Last Updated: 2017-09-08

Results Overview

If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure shows MTD for cyclophosphamide, bortezomib and doxorubicin. MTD for dexamethasone is include in a separate table due to the different Unit of Measure.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Up to 90 days after initiation of study treatment

Results posted on

2017-09-08

Participant Flow

Participant milestones

Participant milestones
Measure	Relapsed Disease (Cohort I) Patients with relapsed multiple myeloma receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cyclophosphamide: Given IV or PO pegylated liposomal doxorubicin hydrochloride: Given IV bortezomib: Given IV dexamethasone: Given IV or PO	Newly Diagnosed Disease (Cohort II) Patients with newly diagnosed multiple myeloma receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cyclophosphamide: Given IV or PO pegylated liposomal doxorubicin hydrochloride: Given IV bortezomib: Given IV dexamethasone: Given IV or PO
Overall Study STARTED	6	25
Overall Study COMPLETED	5	24
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pegylated Liposomal Doxorubicin Hydrochloride, Bortezomib, Cyclophosphamide, and Dexamethasone in Treating Patients With Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Chemotherapy and Enzyme Inhibitor) n=31 Participants Patients receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cyclophosphamide: Given IV or PO pegylated liposomal doxorubicin hydrochloride: Given IV bortezomib: Given IV dexamethasone: Given IV or PO
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 90 days after initiation of study treatment

Population: Patients with relapsed multiple myeloma who received cyclophosphomide, bortezomib, liposomal doxorubicin and dexamethasone. Note that the MTD for dexamethasone is in a separate table due to the different dosing unit.

Outcome measures

Outcome measures
Measure	Relapsed Disease n=6 Participants Patients with relapsed multiple myeloma receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cyclophosphamide: Given IV or PO pegylated liposomal doxorubicin hydrochloride: Given IV bortezomib: Given IV dexamethasone: Given IV or PO
Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1) [MTD Cyclophosphamide, MTD Bortezmib, MTD Docxorubicin] MTD cyclophosphamide	300 mg/m2
Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1) [MTD Cyclophosphamide, MTD Bortezmib, MTD Docxorubicin] MTD bortezomib	1.6 mg/m2
Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1) [MTD Cyclophosphamide, MTD Bortezmib, MTD Docxorubicin] MTD liposomal doxorubicin	30 mg/m2

PRIMARY outcome

Timeframe: up to 28 days after last cycle of treatment

Population: Newly diagnosed patients (cohort II)

Disease response using Blade Multiple Myeloma Response Criteria in newly diagnosed (Cohort II) patients who completed at least one cycle of treatment. There were 24 evaluable patients in Cohort II.

Outcome measures

Outcome measures
Measure	Relapsed Disease n=24 Participants Patients with relapsed multiple myeloma receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cyclophosphamide: Given IV or PO pegylated liposomal doxorubicin hydrochloride: Given IV bortezomib: Given IV dexamethasone: Given IV or PO
Disease Response Rate (Cohort II) Complete response (CR)	2 Participants
Disease Response Rate (Cohort II) Near complete response (nCR)	2 Participants
Disease Response Rate (Cohort II) Very good partial response (VGPR)	3 Participants
Disease Response Rate (Cohort II) Partial response (PR)	11 Participants
Disease Response Rate (Cohort II) Stable disease (SD)	6 Participants

PRIMARY outcome

Timeframe: Up to 90 days after initiation of study treatment

Population: Patients with relapsed multiple myeloma who received cyclophosphomide, bortezomib, liposomal doxorubicin and dexamethasone. Note that this Outcome Measure will only describe the MTD for dexamethasone. Dexamethasone could not be reported with the MTD for the other three drugs due to a different Unit of Measure.

If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure will only describe the MTD for dexamethasone. Dexamethasone could not be reported with the MTD for the other three drugs due to a different Unit of Measure.

Outcome measures

Outcome measures
Measure	Relapsed Disease n=6 Participants Patients with relapsed multiple myeloma receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cyclophosphamide: Given IV or PO pegylated liposomal doxorubicin hydrochloride: Given IV bortezomib: Given IV dexamethasone: Given IV or PO
Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1). [Dexamethasone MTD]	40 mg

Adverse Events

Treatment (Chemotherapy and Enzyme Inhibitor)

Serious events: 1 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Chemotherapy and Enzyme Inhibitor) n=31 participants at risk Patients receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cyclophosphamide: Given IV or PO pegylated liposomal doxorubicin hydrochloride: Given IV bortezomib: Given IV dexamethasone: Given IV or PO
Vascular disorders Thromboembolic event	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded

Other adverse events

Other adverse events
Measure	Treatment (Chemotherapy and Enzyme Inhibitor) n=31 participants at risk Patients receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. cyclophosphamide: Given IV or PO pegylated liposomal doxorubicin hydrochloride: Given IV bortezomib: Given IV dexamethasone: Given IV or PO
Infections and infestations Hand foot and mouth disease	12.9% 4/31 • Number of events 4 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Infections and infestations Urinary tract infection	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Infections and infestations Infection without neutropenia	6.5% 2/31 • Number of events 2 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Gastrointestinal disorders Gastrointestinal hemorrhage	6.5% 2/31 • Number of events 2 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Respiratory, thoracic and mediastinal disorders Acute exacerbation of COPD	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Non-cardiac chest pain	6.5% 2/31 • Number of events 2 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Renal and urinary disorders Urinary incontinence	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Skin and subcutaneous tissue disorders Blistering hands	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Blood and lymphatic system disorders Anemia	25.8% 8/31 • Number of events 8 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Investigations Weight loss	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Nervous system disorders Peripheral neuropathy	22.6% 7/31 • Number of events 7 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Gastrointestinal disorders Nausea	32.3% 10/31 • Number of events 10 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Gastrointestinal disorders Constipation	32.3% 10/31 • Number of events 10 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Skin and subcutaneous tissue disorders Peeling hands	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Jaw pain	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Upper arm pain	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Fatigue	58.1% 18/31 • Number of events 18 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Chest tightness	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Respiratory, thoracic and mediastinal disorders Dyspnea	6.5% 2/31 • Number of events 2 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Psychiatric disorders Insomnia	9.7% 3/31 • Number of events 3 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Respiratory, thoracic and mediastinal disorders Lung infection	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Investigations Transaminitis	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Investigations Hypoalbuminemia	16.1% 5/31 • Number of events 5 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Leg pain	6.5% 2/31 • Number of events 2 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Skin and subcutaneous tissue disorders Rash	6.5% 2/31 • Number of events 2 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Edema limbs	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Gastrointestinal disorders Diarrhea	9.7% 3/31 • Number of events 3 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Eye disorders Vomiting	9.7% 3/31 • Number of events 3 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Gastrointestinal disorders Mucositis	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Skin and subcutaneous tissue disorders Skin changes	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Investigations Leukopenia	12.9% 4/31 • Number of events 4 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Weakness	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Shoulder pain	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Psychiatric disorders Anxiety	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Back pain	9.7% 3/31 • Number of events 3 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Investigations Neutropenia	16.1% 5/31 • Number of events 5 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Investigations Hypophosphatemia	9.7% 3/31 • Number of events 3 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Infections and infestations Candidas	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Investigations Hyponatremia	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Investigations Hypocalcemia	9.7% 3/31 • Number of events 3 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
General disorders Hiccoughs	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Skin and subcutaneous tissue disorders Hives	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Nervous system disorders Dizziness	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Nervous system disorders Cognitive disturbance	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Infections and infestations Upper respiratory infection	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Infections and infestations Fungal skin infection	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Respiratory, thoracic and mediastinal disorders Epistaxis	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Musculoskeletal and connective tissue disorders Muscle cramps	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Metabolism and nutrition disorders Dehydration	6.5% 2/31 • Number of events 2 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Musculoskeletal and connective tissue disorders Muscle pain	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded
Investigations Lymphopenia	3.2% 1/31 • Number of events 1 • Through 45 days after the last dose of study drug. \>= grade 2 events are recorded

Additional Information

Dr. Pamela Becker

University of Washington

Phone: 206-616-1589

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60