Velcade (Bortezomib), Adriamycin Dexamethasone (PAD) or Vincristine Adriamycin Dexamethasone in Second Line Treatment of Multiple Myeloma

• Sponsor: Janssen-Cilag International NV (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00441168
• Collaborator: (none)
• Enrollment: 30
• Locations: 16
• Arms: 2
• Duration (Months): 13
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research study is to test the safety and effectiveness of replacing vincristine with a drug called bortezomib (also known as "Velcade"or PS341) in the standard therapy vincristine, doxorubicin (not limited to, but formerly referred to under the tradename Adriamycin) and dexamethasone (VAD) in patients with multiple myeloma. Multiple Myeloma is the second most common cancer of the blood. Bortezomib is the first approved cancer treatment in a new class of medicines called proteasome inhibitors. It disrupts the cell cycle of the cell, affecting numerous biologic pathways, including those related to growth and survival of cancer cells. The treatment will be used as second line treatment, which means either the disease has returned after a period of improvement (relapse) or the disease did not respond to the initial treatment (refractory). Patients will receive either bortezomib (PS341), doxorubicin (Adriamycin) and dexamethasone (PAD) or the VAD standard therapy.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: adriamycin; Drug: bortezomib; Drug: dexamethasone; Drug: vincristine	Phase 2

Detailed Description

Bortezomib, has been approved for use in patients with multiple myeloma, who have already received at least one prior treatment and whose disease is worsening on their last treatment and who have already undergone or are unsuitable for bone marrow transplantation. Bortezomib has significant activity in patients with relapsed multiple myeloma, its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin. The VAD combination has been widely used in multiple myeloma and has demonstrated to be effective in relapsed patients. Based on previous trial results, it is hoped that bortezomib, in replacing vincristine in the VAD standard therapy, can improve the response to treatment of patients with multiple myeloma, with manageable side effects. This is an international, multicentre, randomised, open-label, parallel group study. About 212 patients will take part in the study. Patients will be treated with either bortezomib (PS-341), Adriamycin and Dexamethasone (PAD) or Vincristine, Adriamycin and Dexamethasone (VAD). There will be an initial 14 day screening period to evaluate if the patient is suitable for the study. After screening, eligible patients will be randomised to receive either PAD or VAD. Patients will receive therapy for up to 8 treatment cycles of 28 days each. After the treatment period, there will be a long-term follow-up period with monthly visits until disease progression or relapse. Thereafter follow-up will be continued by at least a phone call every other month. This long-term follow-up period will be performed for all patients until the last patient was treated and followed up for 1 year. Response to treatment will be assessed according to the European group for blood and marrow transplant criteria (EBMT). Disease burden will be monitored by measuring M-protein concentration in serum and in urine every 4 weeks until disease progression or relapse. Thereafter follow-up for survival will be continued every other month by at least a phone call. Safety will be assessed by monitoring of adverse events (AEs), vital signs, physical examination and clinical laboratory tests. Treatment with PAD or VAD will be for up to 8 cycles of 28 days each. Treatment beyond 6 cycles will be discussed on individual basis. Proposed dosages are: bortezomib 1.3 mg/m² intravenous (IV) bolus on Days 1, 4, 8, and 11; vincristine 0.4mg IV push on Days 1 to 4; doxorubicin 9mg/m² IV push on Days 1 to 4; dexamethasone in 1st cycle 40 mg daily on Days 1 to 4, 9 to 12 and 17 to 20, orally (or equivalent parenteral dose) and on subsequent cycles as 40 mg daily on Days 1 to 4 and 17 to 20 only.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicentre, Randomised, Open-Label, Parallel Group Study to Evaluate the Safety and Efficacy of Velcade When Added to Adriamycin-Dexamethasone Treatment Versus Vincristine-Adriamycin-Dexamethasone Standard Treatment in Subjects With Multiple Myeloma Who Are Refractory to or Have Relapsed After Primary Therapy for Multiple Myeloma
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: VAD Treatment vincristine in combination with adriamycin and dexamethasone	Drug: adriamycin; adriamycin: 9mg/m² intravenous (IV) push on days 1 to 4; Drug: dexamethasone; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle; Drug: vincristine; vincristine: 0.4mg IV push on days 1 to 4
Experimental: PAD Treatment bortezomib in combination with adriamycin and dexamethasone	Drug: adriamycin; adriamycin: 9mg/m² intravenous (IV) push on days 1 to 4; Drug: bortezomib; bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11; Drug: dexamethasone; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle

Outcome Measures

Primary Outcome Measures

1. Best Confirmed Disease Response [every 28 days during treatment period for up to 6 to 8 cycles]

   The primary efficacy analysis was based on the best response obtained during the treatment period according to the European Group for Blood and Marrow Transplantation (EBMT) criteria as assessed by the investigator. The best confirmed response was defined as 2 separate and consecutive evaluations of response, at least 6 weeks apart (for progressive disease [PD], 1 to 3 weeks apart). The ordering of the responses was: complete response (CR), partial response (PR), minimal response (MR), no change (NC) and PD. CR was the best response and the poorest response was PD.

2. Best Reported Disease Response [every 28 days during treatment period for up to 6 to 8 cycles]

   The primary efficacy analysis was based on the best response obtained during the treatment period according to the EBMT criteria as assessed by the investigator. The ordering of the responses was: CR, PR, MR, NC and PD. CR was the best response and the poorest response was PD.

Secondary Outcome Measures

1. Duration of Response (DOR) [every 28 days during treatment period for up to 6 to 8 cycles]

   DOR was defined as the duration from the date of the best confirmed response for subjects who achieved CR or PR to the date of first documented evidence of PD (or relapse for subjects who experienced CR) over the duration of the study. DOR = ([Date of PD or date of censoring - Date of best response]+1)/30.44.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Relapsed or refractory multiple myeloma following 1 previous line of therapy and, is scheduled by the investigator to be treated with vincristine, adriamycin and dexamethasone standard therapy

• measurable secretory multiple myeloma based on defined criteria

• Karnofsky performance status of >or = 60%

• fulfils defined laboratory requirements within 14 days before baseline

• if female, the patient is either postmenopausal or surgically sterilised or willing to use an acceptable method of birth control for defined period of time

• if male, the patient agrees to use an acceptable barrier method for contraception for a defined period of time.

Exclusion Criteria:

• More than one previous line of therapy for multiple myeloma

• use of bortezomib in the previous line of therapy and/or received bortezomib in a previous trial

• known allergy or hypersensitivity to bortezomib, boron or mannitol

• peripheral neuropathy or neuropathic pain of grade 2 or higher

• myocardial infarction within 6 months of enrollment or had New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Zagreb		Croatia
2		Leer		Germany
3		Velbert		Germany
4		Debrecen		Hungary
5		Kaunas		Lithuania
6		Klaipeda		Lithuania
7		Vilnius		Lithuania
8		Bialystok		Poland
9		Gdansk		Poland
10		Poznan		Poland
11		Moscow		Russian Federation
12		Samara		Russian Federation
13		St Petersburg		Russian Federation
14		Ankara		Turkey
15		Bursa		Turkey
16		Eskisehir		Turkey

Sponsors and Collaborators

• Janssen-Cilag International NV

Investigators

• Study Director: Janssen-Cilag International NV Clinical Trial, Janssen-Cilag International NV

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen-Cilag International NV
• ClinicalTrials.gov Identifier: NCT00441168
• Other Study ID Numbers: CR011065; 26866138MMY2038; 2006-001709-27
• First Posted: Feb 28, 2007
• Last Update Posted: Mar 21, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by Janssen-Cilag International NV: Multiple Myeloma; bortezomib; Cancer; Hematology; bone marrow; immunoglobulin; relapse; refractory; plasma cell; Velcade; adriamycin; dexamethasone; vincristine
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Vincristine; Doxorubicin; Liposomal doxorubicin; Bortezomib

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 05 December 2006 to 04 July 2007 at 2 sites in Germany, 1 site in Hungary, 3 sites in Lithuania, 3 sites in Poland and 3 sites in Russia
Pre-assignment Detail	Subjects who qualified were screened. Subjects were considered for eligibility when the investigator would treat the subject with a combination therapy of vincristine, adriamycin and dexamethasone (VAD) standard therapy. One subject was not randomised because the subject was a screening failure.

Arm/Group Title	VAD Treatment	PAD Treatment
Arm/Group Description	vincristine: 0.4mg IV push on days 1 to 4; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle	bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle
Period Title: Treatment Period
STARTED	17	13
TREATED	16	13
COMPLETED	6	7
NOT COMPLETED	11	6
Period Title: Treatment Period
STARTED	17	13
COMPLETED	5	4
NOT COMPLETED	12	9

Baseline Characteristics

Arm/Group Title	VAD Treatment	PAD Treatment	Total
Arm/Group Description	vincristine: 0.4mg IV push on days 1 to 4; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle	bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle	Total of all reporting groups
Overall Participants	16	13	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (9.4)	61.5 (11.3)	62.9 (10.2)
Sex: Female, Male (Count of Participants)
Female	5 31.3%	3 23.1%	8 27.6%
Male	11 68.8%	10 76.9%	21 72.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	16 100%	13 100%	29 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Karnofsky Performance Status (participants) [Number]
≤50	0 0%	0 0%	0 0%
60	1 6.3%	1 7.7%	2 6.9%
70	1 6.3%	3 23.1%	4 13.8%
80	9 56.3%	3 23.1%	12 41.4%
90	5 31.3%	3 23.1%	8 27.6%
100	0 0%	3 23.1%	3 10.3%
Body Surface Area (m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m2]	1.855 (0.233)	1.924 (0.219)	1.886 (0.226)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	168.8 (11.2)	169.8 (9.5)	169.3 (10.3)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	75.9 (15.7)	78.3 (14.5)	77.0 (15.0)

Outcome Measures

1. Primary Outcome

Title	Best Confirmed Disease Response
Description	The primary efficacy analysis was based on the best response obtained during the treatment period according to the European Group for Blood and Marrow Transplantation (EBMT) criteria as assessed by the investigator. The best confirmed response was defined as 2 separate and consecutive evaluations of response, at least 6 weeks apart (for progressive disease [PD], 1 to 3 weeks apart). The ordering of the responses was: complete response (CR), partial response (PR), minimal response (MR), no change (NC) and PD. CR was the best response and the poorest response was PD.
Time Frame	every 28 days during treatment period for up to 6 to 8 cycles

Outcome Measure Data

Analysis Population Description

Subjects in the ITT population (all subjects who received at least one dose of study drug and who had at least one post baseline efficacy parameter) were included.

Arm/Group Title	VAD Treatment	PAD Treatment
Arm/Group Description	vincristine: 0.4mg IV push on days 1 to 4; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle	bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle
Measure Participants	15	13
CR	0 0%	1 7.7%
PR	5 31.3%	6 46.2%
Response Rate (CR + PR)	5 31.3%	7 53.8%
MR	2 12.5%	0 0%
Overall Response (CR + PR + MR)	7 43.8%	7 53.8%
NC	3 18.8%	1 7.7%
PD	1 6.3%	1 7.7%
Unknown/Unable to Assess	4 25%	4 30.8%

2. Primary Outcome

Title	Best Reported Disease Response
Description	The primary efficacy analysis was based on the best response obtained during the treatment period according to the EBMT criteria as assessed by the investigator. The ordering of the responses was: CR, PR, MR, NC and PD. CR was the best response and the poorest response was PD.
Time Frame	every 28 days during treatment period for up to 6 to 8 cycles

Outcome Measure Data

Analysis Population Description

Subjects in the ITT population (all subjects who received at least one dose of study drug and who had at least one post baseline efficacy parameter) were included.

Arm/Group Title	VAD Treatment	PAD Treatment
Arm/Group Description	vincristine: 0.4mg IV push on days 1 to 4; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle	bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle
Measure Participants	15	13
CR	1 6.3%	3 23.1%
PR	6 37.5%	4 30.8%
Response Rate (CR + PR)	7 43.8%	7 53.8%
MR	2 12.5%	3 23.1%
Overall Response (CR + PR + MR)	9 56.3%	10 76.9%
NC	5 31.3%	3 23.1%
PD	0 0%	0 0%
Unknown/Unable to Assess	1 6.3%	0 0%

3. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR was defined as the duration from the date of the best confirmed response for subjects who achieved CR or PR to the date of first documented evidence of PD (or relapse for subjects who experienced CR) over the duration of the study. DOR = ([Date of PD or date of censoring - Date of best response]+1)/30.44.
Time Frame	every 28 days during treatment period for up to 6 to 8 cycles

Outcome Measure Data

Analysis Population Description

Subjects in the ITT population (all subjects who received at least one dose of study drug and who had at least one post baseline efficacy parameter) were included.There was insufficient data to perform Kaplan Meier analysis (data available for 5 subjects in the VAD group and 6 subjects in the PAD group).

Arm/Group Title	VAD Treatment	PAD Treatment
Arm/Group Description	vincristine: 0.4mg IV push on days 1 to 4; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle	bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle
Measure Participants	5	6
patient 1	1.68	2.83
patient 2	6.18	7.69
patient 3	3.71	5.52
patient 4	5.42	6.57
patient 5	4.73	4.96
patient 6	NA	7.42

Adverse Events

Time Frame	For up to 6 to 8 cycles, consisting of 28 days each, and for up to a 1-year follow-up period
Arm/Group Title	VAD Treatment		PAD Treatment
Arm/Group Description	vincristine: 0.4mg IV push on days 1 to 4; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle		bortezomib: 1.3 mg/m² intravenous (IV) bolus on days 1, 4, 8, and 11; adriamycin: 9mg/m² IV push on days 1 to 4; dexamethasone: 40 mg daily days 1- 4/9-12/17-20 - cycle 1 / days 1-4/17-20 - subsequent cycle
All Cause Mortality
	VAD Treatment		PAD Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	VAD Treatment		PAD Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)		5/13 (38.5%)
Blood and lymphatic system disorders
Neutropenia	1/16 (6.3%)	1	1/13 (7.7%)	1
Thrombocytopenia	0/16 (0%)	0	1/13 (7.7%)	1
Cardiac disorders
Angina unstable	0/16 (0%)	0	1/13 (7.7%)	1
Cardiac failure chronic	0/16 (0%)	0	1/13 (7.7%)	1
Supraventricular tachycardia	0/16 (0%)	0	1/13 (7.7%)	1
Gastrointestinal disorders
Diarrhoea	0/16 (0%)	0	1/13 (7.7%)	1
Vomiting	0/16 (0%)	0	1/13 (7.7%)	2
General disorders
Asthenia	0/16 (0%)	0	1/13 (7.7%)	2
Death	1/16 (6.3%)	1	0/13 (0%)	0
Sudden cardiac death	1/16 (6.3%)	1	0/13 (0%)	0
Infections and infestations
Bronchitis acute	1/16 (6.3%)	1	0/13 (0%)	0
Bursitis infective	0/16 (0%)	0	1/13 (7.7%)	1
Pneumonia	2/16 (12.5%)	2	1/13 (7.7%)	2
Pyelonephritis acute	0/16 (0%)	0	1/13 (7.7%)	1
Septic shock	1/16 (6.3%)	1	0/13 (0%)	0
Injury, poisoning and procedural complications
Spinal fracture	1/16 (6.3%)	1	0/13 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/16 (6.3%)	1	0/13 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/16 (6.3%)	1	0/13 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/16 (6.3%)	1	0/13 (0%)	0
Cough	0/16 (0%)	0	1/13 (7.7%)	1
Respiratory failure	0/16 (0%)	0	1/13 (7.7%)	1
Other (Not Including Serious) Adverse Events
	VAD Treatment		PAD Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/16 (93.8%)		8/13 (61.5%)
Blood and lymphatic system disorders
Anaemia	1/16 (6.3%)	1	1/13 (7.7%)	2
Leukocytosis	0/16 (0%)	0	1/13 (7.7%)	2
Leukopenia	2/16 (12.5%)	3	0/13 (0%)	0
Lymphopenia	4/16 (25%)	11	2/13 (15.4%)	7
Neutropenia	4/16 (25%)	9	1/13 (7.7%)	3
Thrombocytopenia	1/16 (6.3%)	1	1/13 (7.7%)	4
Ear and labyrinth disorders
Vertigo	2/16 (12.5%)	2	0/13 (0%)	0
Eye disorders
Eye irritation	0/16 (0%)	0	1/13 (7.7%)	1
Visual acuity reduced	1/16 (6.3%)	1	0/13 (0%)	0
Gastrointestinal disorders
Constipation	1/16 (6.3%)	4	0/13 (0%)	0
Diarrhoea	2/16 (12.5%)	2	1/13 (7.7%)	1
General disorders
Asthenia	1/16 (6.3%)	1	1/13 (7.7%)	1
Extravasation	1/16 (6.3%)	1	0/13 (0%)	0
Face oedema	0/16 (0%)	0	1/13 (7.7%)	1
Fatigue	3/16 (18.8%)	4	2/13 (15.4%)	2
Oedema peripheral	1/16 (6.3%)	2	1/13 (7.7%)	1
Pyrexia	0/16 (0%)	0	1/13 (7.7%)	1
Infections and infestations
Abscess limb	1/16 (6.3%)	1	0/13 (0%)	0
Bronchitis acute	2/16 (12.5%)	2	1/13 (7.7%)	1
Cystitis	1/16 (6.3%)	1	0/13 (0%)	0
Herpes simplex	1/16 (6.3%)	1	0/13 (0%)	0
Herpes zoster	0/16 (0%)	0	1/13 (7.7%)	1
Infection	1/16 (6.3%)	2	0/13 (0%)	0
Nasopharyngitis	1/16 (6.3%)	1	0/13 (0%)	0
Pneumonia	0/16 (0%)	0	1/13 (7.7%)	1
Respiratory tract infection	2/16 (12.5%)	2	0/13 (0%)	0
Viral infection	1/16 (6.3%)	1	0/13 (0%)	0
Investigations
White blood cell count increased	1/16 (6.3%)	1	0/13 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus	0/16 (0%)	0	1/13 (7.7%)	1
Hyperglycaemia	1/16 (6.3%)	1	1/13 (7.7%)	1
Hypocalcaemia	0/16 (0%)	0	1/13 (7.7%)	2
Musculoskeletal and connective tissue disorders
Back pain	2/16 (12.5%)	3	1/13 (7.7%)	1
Bone pain	1/16 (6.3%)	1	1/13 (7.7%)	1
Bursitis	0/16 (0%)	0	1/13 (7.7%)	1
Pain in extremity	0/16 (0%)	0	1/13 (7.7%)	1
Shoulder pain	1/16 (6.3%)	1	0/13 (0%)	0
Nervous system disorders
Ageusia	1/16 (6.3%)	1	0/13 (0%)	0
Neuropathy peripheral	0/16 (0%)	0	1/13 (7.7%)	1
Peripheral sensory neuropathy	1/16 (6.3%)	3	2/13 (15.4%)	4
Psychiatric disorders
Anxiety	1/16 (6.3%)	1	0/13 (0%)	0
Insomnia	2/16 (12.5%)	2	4/13 (30.8%)	5
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/16 (6.3%)	1	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/16 (6.3%)	1	0/13 (0%)	0
Night sweats	1/16 (6.3%)	1	0/13 (0%)	0
Vascular disorders
Hypertension	1/16 (6.3%)	1	2/13 (15.4%)	2
Thrombophlebitis	1/16 (6.3%)	2	0/13 (0%)	0
Venous thrombosis limb	1/16 (6.3%)	1	0/13 (0%)	0

Limitations/Caveats

Due to a substantial decline in the use of the VAD regimen as standard of care, recruitment of the study was halted at 30 subjects. It was not possible to statistically evaluate any long term efficacy parameter.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.