Trial Outcomes & Findings for Combination Study of Revlimid®, Velcade® Dexamethasone and Doxil® (RVDD)for Newly Diagnosed Multiple Myeloma (NCT NCT00724568)

Last Updated: 2017-06-02

Results Overview

Dose Level 1: 15 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12\* and 20 mg/m2 Doxil daily on day 4 Dose Level 2: 20 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12\* and 20 mg/m2 Doxil daily on day 4 Dose Level 3: 25 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12\* and 20 mg/m2 Doxil daily on day 4 Dose Level 4: 25 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12\* and 30 mg/m2 Doxil daily on day 4

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

74 participants

Primary outcome timeframe

1 month post treatment

Results posted on

2017-06-02

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at indicated doses on day 4, Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels, and Revlimid at indicated doses on days 1-14 in 3-week cycles for 4-8 cycles.	Phase II Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at indicated doses on day 4, Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels, and Revlimid at indicated doses on days 1-14 in 3-week cycles for 4-8 cycles.
Overall Study STARTED	42	32
Overall Study COMPLETED	42	32
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Study of Revlimid®, Velcade® Dexamethasone and Doxil® (RVDD)for Newly Diagnosed Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Combination Drug Therapy n=72 Participants Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at indicated doses on day 4, Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels, and Revlimid at indicated doses on days 1-14 in 3-week cycles for 4-8 cycles.
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 month post treatment

Population: A total of 74 patients were enrolled in this phase 1/2 study: 42 in phase 1.

Outcome measures

Outcome measures
Measure	Combination Drug Therapy n=42 Participants Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at indicated doses on day 4, Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels, and Revlimid at indicated doses on days 1-14 in 3-week cycles for 4-8 cycles.
Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD) Revlimid	25 mg
Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD) VELCADE	1.3 mg
Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD) Dexamethasone	20 mg
Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD) Doxil	30 mg

SECONDARY outcome

Timeframe: 24 weeks (8, 21-day cycles)

Population: 74 patients were enrolled, but 2 were not evaluable for dose limiting toxicities. 72 patients were included in this analysis.

Partial Response: * 50% reduction in the level of serum monoclonal protein for at least two determinations six weeks apart. * If present, reduction in 24-hour urinary light chain excretion by either, greater than or equal to 90%, or to \<200 mg for at least two determinations six weeks apart. * 50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least six weeks. * No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response). Complete Response: * Disappearance of the original monoclonal protein from the blood and urine on at least two determinations for a minimum of six weeks. * \<5% plasma cells in the bone marrow on at least two determinations for a minimum of six weeks. * No increase in the size or number of lytic bone lesions.

Outcome measures

Outcome measures
Measure	Combination Drug Therapy n=72 Participants Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at indicated doses on day 4, Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels, and Revlimid at indicated doses on days 1-14 in 3-week cycles for 4-8 cycles.
The Percentage of Patients That Achieved Partial or Complete Response to Treatment.	96 percentage of patients

Adverse Events

Combination Drug Therapy

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Combination Drug Therapy n=74 participants at risk Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at indicated doses on day 4, Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels, and Revlimid at indicated doses on days 1-14 in 3-week cycles for 4-8 cycles.
Respiratory, thoracic and mediastinal disorders Lung Hemorrhage	1.4% 1/74 • Number of events 1 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Infections and infestations Pneumonia with Grade 3 or 4 Neutropenia	1.4% 1/74 • Number of events 1 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Infections and infestations Pneumonia with Normal Absolute Neutrophil Count	1.4% 1/74 • Number of events 1 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.4% 1/74 • Number of events 1 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.

Other adverse events

Other adverse events
Measure	Combination Drug Therapy n=74 participants at risk Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at indicated doses on day 4, Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels, and Revlimid at indicated doses on days 1-14 in 3-week cycles for 4-8 cycles.
Blood and lymphatic system disorders Anemia	13.5% 10/74 • Number of events 22 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Blood and lymphatic system disorders Leukocytes (total WBC)	8.1% 6/74 • Number of events 11 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Blood and lymphatic system disorders Lymphopenia	6.8% 5/74 • Number of events 12 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	5.4% 4/74 • Number of events 5 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Blood and lymphatic system disorders Platelets	8.1% 6/74 • Number of events 12 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
General disorders Fatigue (asthenia, lethargy, malaise)	23.0% 17/74 • Number of events 32 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Skin and subcutaneous tissue disorders Rash/desquamation	6.8% 5/74 • Number of events 5 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Gastrointestinal disorders Constipation	13.5% 10/74 • Number of events 14 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Gastrointestinal disorders Diarrhea	8.1% 6/74 • Number of events 12 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Gastrointestinal disorders Nausea	13.5% 10/74 • Number of events 11 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Gastrointestinal disorders Taste alteration (dysgeusia)	5.4% 4/74 • Number of events 6 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
General disorders Edema: limb	8.1% 6/74 • Number of events 6 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Metabolism and nutrition disorders ALT, SGPT (serum glutamic pyruvic transaminase)	8.1% 6/74 • Number of events 9 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	6.8% 5/74 • Number of events 9 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	8.1% 6/74 • Number of events 12 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	5.4% 4/74 • Number of events 8 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	5.4% 4/74 • Number of events 9 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	6.8% 5/74 • Number of events 6 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	6.8% 5/74 • Number of events 5 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Nervous system disorders Dizziness	9.5% 7/74 • Number of events 7 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Nervous system disorders Mood alteration	6.8% 5/74 • Number of events 5 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Nervous system disorders Neuropathy: sensory	9.5% 7/74 • Number of events 15 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Nervous system disorders Pain	5.4% 4/74 • Number of events 5 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Respiratory, thoracic and mediastinal disorders Cough	9.5% 7/74 • Number of events 9 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	8.1% 6/74 • Number of events 7 Adverse events were captured collectively for the study, not by arm, because both arms received the same drugs.

Additional Information

Dr. Moshe Talpaz

University of Michigan Comprehensive Cancer Center

Phone: 734-764-8195

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place