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Trial record 10 of 107 for:    "Vascular Hemostatic Disease" | "Doxorubicin"

Pegylated Liposomal Doxorubicin, Low Freq Dexamethasone & Revlimid (Dd-R) in Newly Diagnosed Multiple Myeloma (MM)

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ClinicalTrials.gov Identifier: NCT00617591
Recruitment Status : Completed
First Posted : February 18, 2008
Results First Posted : December 17, 2013
Last Update Posted : January 17, 2014
Sponsor:
Collaborators:
Celgene Corporation
Ortho Biotech Clinical Affairs, L.L.C.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Lenalidomide
Drug: Pegylated Liposomal Doxorubicin (PLD)
Drug: Dexamethasone
Enrollment 57
Recruitment Details 57 Eligible participants were enrolled at Moffitt Cancer Center between February 2008 and February 2011.
Pre-assignment Details  
Arm/Group Title Induction and Maintenance Therapy
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Induction Phase Followed by Maintenance Therapy.

Patients received lenalidomide 25 mg orally on days 1-21, dexamethasone 40 mg orally on days on 1-4, and Pegylated Liposomal Doxorubicin (PLD) 40 mg/m^2 intravenously on day 1 (reduced to 30 mg/m^2 after the initial 29 patients were treated). Cycles were repeated every 28 days.

At the best response (4-8 cycles of induction), patients could proceed with either high-dose therapy or maintenance with lenalidomide and dexamethasone at the tolerated doses on the same schedule until disease progression.

Dd-R: Lenalidomide (Revlimid®) combined with Pegylated Liposomal Doxorubicin (Doxil®) and Dexamethasone (Decadron®) as outlined in the Detailed Description.

Period Title: Overall Study
Started 57
Completed 47
Not Completed 10
Reason Not Completed
Withdrew consent during Induction             4
Withdrew consent during Maintenance             6
Arm/Group Title Induction and Maintenance Therapy
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Induction Phase Followed by Maintenance Therapy.

Patients received lenalidomide 25 mg orally on days 1-21, dexamethasone 40 mg orally on days on 1-4, and PLD 40 mg/m^2 intravenously on day 1 (reduced to 30 mg/m^2 after the initial 29 patients were treated). Cycles were repeated every 28 days.

At the best response (4-8 cycles of induction), patients could proceed with either high-dose therapy or maintenance with lenalidomide and dexamethasone at the tolerated doses on the same schedule until disease progression.

Dd-R: Lenalidomide (Revlimid®) combined with Pegylated Liposomal Doxorubicin (Doxil®) and Dexamethasone (Decadron®) as outlined in the Detailed Description.

Overall Number of Baseline Participants 57
Hide Baseline Analysis Population Description
All participants
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants
<=18 years
0
   0.0%
Between 18 and 65 years
37
  64.9%
>=65 years
20
  35.1%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 57 participants
63
(36 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants
Female
26
  45.6%
Male
31
  54.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 57 participants
57
1.Primary Outcome
Title Overall Response Rate (ORR) - Percentage of Participants With Partial Response or Better With Induction Regimen
Hide Description ORR assessed using International Myeloma Working Group Response Definitions. Partial Remission (PR): A greater than 50% reduction in the serum paraprotein, and if present, a greater than 90% reduction in the urine M protein excretion. Patients must also have a decrease by 50% in the size of soft tissue plasmacytoma. If serum and urine M protein are not measurable, a 50% or greater decreased in the difference of the involved and uninvolved free light chain. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared.
Time Frame 24 Months
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All participants
Arm/Group Title Induction and Maintenance Therapy
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Induction Phase Followed by Maintenance Therapy.

Patients received lenalidomide 25 mg orally on days 1-21, dexamethasone 40 mg orally on days on 1-4, and Pegylated Liposomal Doxorubicin (PLD) 40 mg/m^2 intravenously on day 1 (reduced to 30 mg/m^2 after the initial 29 patients were treated). Cycles were repeated every 28 days.

At the best response (4-8 cycles of induction), patients could proceed with either high-dose therapy or maintenance with lenalidomide and dexamethasone at the tolerated doses on the same schedule until disease progression.

Dd-R: Lenalidomide (Revlimid®) combined with Pegylated Liposomal Doxorubicin (Doxil®) and Dexamethasone (Decadron®) as outlined in the Detailed Description.

Overall Number of Participants Analyzed 57
Measure Type: Number
Unit of Measure: percentage of participants
77.2
2.Primary Outcome
Title Percentage of Participants With Very Good Partial Remission (VGPR) or Better
Hide Description Quality of response: % Complete Response (CR) + Very Good Partial Remission (VGPR) to induction Dd-R as assessed using International Myeloma Working Group Response Definitions. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared.
Time Frame 24 Months
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Hide Analysis Population Description
All participants
Arm/Group Title Induction and Maintenance Therapy
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Induction Phase Followed by Maintenance Therapy.

Patients received lenalidomide 25 mg orally on days 1-21, dexamethasone 40 mg orally on days on 1-4, and Pegylated Liposomal Doxorubicin (PLD) 40 mg/m^2 intravenously on day 1 (reduced to 30 mg/m^2 after the initial 29 patients were treated). Cycles were repeated every 28 days.

At the best response (4-8 cycles of induction), patients could proceed with either high-dose therapy or maintenance with lenalidomide and dexamethasone at the tolerated doses on the same schedule until disease progression.

Dd-R: Lenalidomide (Revlimid®) combined with Pegylated Liposomal Doxorubicin (Doxil®) and Dexamethasone (Decadron®) as outlined in the Detailed Description.

Overall Number of Participants Analyzed 57
Measure Type: Number
Unit of Measure: percentage of participants
42.1
3.Secondary Outcome
Title Median Progression Free Survival (PFS) in Months
Hide Description PFS: Time from study entry to progression/relapse or death from study entry to death of any cause, assessed using International Myeloma Working Group Response Definitions. Progressive Disease (PD): One of the following criteria must be met: a. Increase of 25% or greater in serum M protein (absolute increase greater or equal to 0.5g/dl); b. Increase of 25% or greater in urine M protein (absolute increase greater than 200 mg/24h); c. Increase of 25% or greater in the difference between the involved and uninvolved free light chain (absolute increase greater than 10 mg/dl); d. Increase of 25% or greater in bone marrow plasma cell percentage (absolute percent greater than 5% in case the patient was in CR and 10% otherwise); i.e. Definite development of new bone lesions or soft tissue plasmacytomas, or increase in the size of existing plasmacytomas by greater or equal to 25%. Development of hypercalcemia (serum calcium > 11.5 mg/dl) attributable only to the plasma cell dyscrasia.
Time Frame 24 Months
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Hide Analysis Population Description
All participants
Arm/Group Title Induction and Maintenance Therapy
Hide Arm/Group Description:

Induction Phase Followed by Maintenance Therapy.

Patients received lenalidomide 25 mg orally on days 1-21, dexamethasone 40 mg orally on days on 1-4, and Pegylated Liposomal Doxorubicin (PLD) 40 mg/m^2 intravenously on day 1 (reduced to 30 mg/m^2 after the initial 29 patients were treated). Cycles were repeated every 28 days.

At the best response (4-8 cycles of induction), patients could proceed with either high-dose therapy or maintenance with lenalidomide and dexamethasone at the tolerated doses on the same schedule until disease progression.

Dd-R: Lenalidomide (Revlimid®) combined with Pegylated Liposomal Doxorubicin (Doxil®) and Dexamethasone (Decadron®) as outlined in the Detailed Description.

Overall Number of Participants Analyzed 57
Median (95% Confidence Interval)
Unit of Measure: months
28
(18.1 to 34.8)
4.Secondary Outcome
Title 2 Year Overall Survival (OS) Rate
Hide Description Percentage of participants with Overall Survival in response to Dd-R in newly diagnosed multiple myeloma patients with active disease. Overall survival is time from study entry to death of any cause.
Time Frame 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title Induction and Maintenance Therapy
Hide Arm/Group Description:

Induction Phase Followed by Maintenance Therapy.

Patients received lenalidomide 25 mg orally on days 1-21, dexamethasone 40 mg orally on days on 1-4, and Pegylated Liposomal Doxorubicin (PLD) 40 mg/m^2 intravenously on day 1 (reduced to 30 mg/m^2 after the initial 29 patients were treated). Cycles were repeated every 28 days.

At the best response (4-8 cycles of induction), patients could proceed with either high-dose therapy or maintenance with lenalidomide and dexamethasone at the tolerated doses on the same schedule until disease progression.

Dd-R: Lenalidomide (Revlimid®) combined with Pegylated Liposomal Doxorubicin (Doxil®) and Dexamethasone (Decadron®) as outlined in the Detailed Description.

Overall Number of Participants Analyzed 57
Measure Type: Number
Unit of Measure: percentage of participants
79.6
5.Secondary Outcome
Title Occurrence of Induction Toxicities
Hide Description

Tolerability of full dose Revlimid® with full dose Doxil® in combination with reduced schedule dexamethasone was to be assessed during Cycle 1 and at the start of Cycle 2 using, whenever possible, the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v3.0.

Due to increased neutropenia and fatigue, toxicities were reviewed after the first 29 participants were enrolled.

Time Frame 24 Months
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Hide Analysis Population Description
First 29 participants with the PLD starting dose of PLD 40 mg/m^2, due to increased neutropenia and fatigue.
Arm/Group Title Induction at Initial Full Dose
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Induction Phase for First 29 Participants

Patients received lenalidomide 25 mg orally on days 1-21, dexamethasone 40 mg orally on days on 1-4, and Pegylated Liposomal Doxorubicin (PLD) 40 mg/m^2 intravenously on day 1.

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: percentage of participants
Percentage with Dose Reductions Required 24
Percentage Receiving < 4 Cycles of Therapy 20
Percentage Who Discontinued After Only 1 Cycle 13.79
Percentage with Grade 3/4 Neutropenia 48
Percentage with Grade 3/4 Fatigue 20
Time Frame 4 years, 10 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Induction and Maintenance Therapy
Hide Arm/Group Description

Induction Phase Followed by Maintenance Therapy.

Patients received lenalidomide 25 mg orally on days 1-21, dexamethasone 40 mg orally on days on 1-4, and PLD 40 mg/m^2 intravenously on day 1 (reduced to 30 mg/m^2 after the initial 29 patients were treated). Cycles were repeated every 28 days.

At the best response (4-8 cycles of induction), patients could proceed with either high-dose therapy or maintenance with lenalidomide and dexamethasone at the tolerated doses on the same schedule until disease progression.

Dd-R: Lenalidomide (Revlimid®) combined with Pegylated Liposomal Doxorubicin (Doxil®) and Dexamethasone (Decadron®) as outlined in the Detailed Description.

All-Cause Mortality
Induction and Maintenance Therapy
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Induction and Maintenance Therapy
Affected / at Risk (%) # Events
Total   26/57 (45.61%)    
Blood and lymphatic system disorders   
Hemoglobin  1  1/57 (1.75%)  1
Neutrophils/granulocytes (ANC/AGC)  1  3/57 (5.26%)  3
Edema: limb  1  1/57 (1.75%)  1
Edema: trunk/genital  1  1/57 (1.75%)  1
Cardiac disorders   
Palpitations  1  1/57 (1.75%)  1
Supraventricular and nodal arrhythmia - Atrial  1  1/57 (1.75%)  1
Cardiac General - Other  1  2/57 (3.51%)  2
Gastrointestinal disorders   
Dehydration  1  1/57 (1.75%)  2
Diarrhea  1  1/57 (1.75%)  2
Nausea  1  1/57 (1.75%)  1
Vomiting  1  1/57 (1.75%)  1
General disorders   
Constitutional Symptoms - Other  1  2/57 (3.51%)  2
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10^9/L)  1  4/57 (7.02%)  6
Pain - NOS  1  1/57 (1.75%)  1
Syndromes - Other  1  1/57 (1.75%)  1
Infections and infestations   
Febrile neutropenia  1  2/57 (3.51%)  2
Infection(documented clinically or microbiologically) w/Grade 3 or 4 neutrophils - Lung(pneumonia)  1  1/57 (1.75%)  1
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Sinus  1  1/57 (1.75%)  1
Infection - Other  1  1/57 (1.75%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils - Bladder (urinary)  1  1/57 (1.75%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils - Blood  1  1/57 (1.75%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils - Foreign body  1  1/57 (1.75%)  1
Infection with normal ANC or Grade 1 or 2 neutrophils - Oral cavity-gums (gingivitis)  1  1/57 (1.75%)  1
Infection with unknown ANC - Lung (pneumonia)  1  1/57 (1.75%)  1
Metabolism and nutrition disorders   
Magnesium, serum-low (hypomagnesemia)  1  1/57 (1.75%)  1
Potassium, serum-low (hypokalemia)  1  2/57 (3.51%)  2
Musculoskeletal and connective tissue disorders   
Fracture  1  4/57 (7.02%)  4
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized  1  1/57 (1.75%)  1
Musculoskeletal/Soft Tissue - Other  1  1/57 (1.75%)  1
Psychiatric disorders   
Confusion  1  1/57 (1.75%)  1
Renal and urinary disorders   
Renal failure  1  1/57 (1.75%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea (shortness of breath)  1  3/57 (5.26%)  3
Pleural effusion (non-malignant)  1  1/57 (1.75%)  1
Pulmonary/Upper Respiratory - Other  1  4/57 (7.02%)  4
Skin and subcutaneous tissue disorders   
Rash/desquamation  1  2/57 (3.51%)  2
Vascular disorders   
Thrombosis/thrombus/embolism  1  4/57 (7.02%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Induction and Maintenance Therapy
Affected / at Risk (%) # Events
Total   56/57 (98.25%)    
Blood and lymphatic system disorders   
Leukocytes (total WBC)  1  42/57 (73.68%)  238
Neutrophils/granulocytes (ANC/AGC)  1  41/57 (71.93%)  244
Hemoglobin  1  25/57 (43.86%)  82
Platelets  1  26/57 (45.61%)  111
Lymphopenia  1  5/57 (8.77%)  20
Edema: limb  1  29/57 (50.88%)  44
Lymphatics - Other  1  3/57 (5.26%)  5
Edema: head and neck  1  3/57 (5.26%)  4
Cardiac disorders   
Hypotension  1  7/57 (12.28%)  11
Eye disorders   
Ocular/Visual - Other  1  5/57 (8.77%)  5
Dry eye syndrome  1  3/57 (5.26%)  3
Gastrointestinal disorders   
Constipation  1  25/57 (43.86%)  35
Diarrhea  1  24/57 (42.11%)  32
Nausea  1  23/57 (40.35%)  33
Anorexia  1  17/57 (29.82%)  20
Gastrointestinal - Other  1  8/57 (14.04%)  15
Vomiting  1  12/57 (21.05%)  17
Taste alteration (dysgeusia)  1  12/57 (21.05%)  16
Dysphagia (difficulty swallowing)  1  7/57 (12.28%)  7
Heartburn/dyspepsia  1  6/57 (10.53%)  6
Dehydration  1  5/57 (8.77%)  6
Dry mouth/salivary gland  1  4/57 (7.02%)  4
Mucositis/stomatitis (clinical exam) - Oral cavity  1  5/57 (8.77%)  5
General disorders   
Fatigue  1  35/57 (61.40%)  60
Sweating (diaphoresis)  1  17/57 (29.82%)  17
Fever (in the absence of neutropenia)  1  13/57 (22.81%)  15
Insomnia  1  14/57 (24.56%)  16
Rigors/chills  1  12/57 (21.05%)  14
Weight Loss  1  4/57 (7.02%)  4
Pain - Head/headache  1  11/57 (19.30%)  11
Pain - Extremity-limb  1  5/57 (8.77%)  6
Pain - Abdomen NOS  1  5/57 (8.77%)  5
Pain - Throat/pharynx/larynx  1  4/57 (7.02%)  6
Pain - Joint  1  3/57 (5.26%)  5
Pain - Muscle  1  3/57 (5.26%)  3
Pain - Oral cavity  1  4/57 (7.02%)  5
Dizziness  1  12/57 (21.05%)  12
Flu-like syndrome  1  4/57 (7.02%)  5
Immune system disorders   
Allergic rhinitis  1  8/57 (14.04%)  8
Infections and infestations   
Febrile neutropenia  1  8/57 (14.04%)  11
Infection with normal ANC or Grade 1 or 2 neutrophils - Vagina  1  3/57 (5.26%)  3
Metabolism and nutrition disorders   
Potassium, serum-low (hypokalemia)  1  5/57 (8.77%)  8
Glucose, serum-high (hyperglycemia)  1  3/57 (5.26%)  10
Potassium, serum-high (hyperkalemia)  1  3/57 (5.26%)  3
Musculoskeletal and connective tissue disorders   
Musculoskeletal/Soft Tissue - Other  1  10/57 (17.54%)  16
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized  1  9/57 (15.79%)  10
Muscle weakness, generalized or specific area (not due to neuropathy) - Extraocular  1  3/57 (5.26%)  3
Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-lower  1  3/57 (5.26%)  3
Nervous system disorders   
Neuropathy: sensory  1  13/57 (22.81%)  16
Neurology - Other  1  6/57 (10.53%)  6
Syncope (fainting)  1  3/57 (5.26%)  3
Tremor  1  7/57 (12.28%)  7
Neuropathy: motor  1  3/57 (5.26%)  3
Psychiatric disorders   
Mood alteration - Depression  1  7/57 (12.28%)  7
Renal and urinary disorders   
Urinary retention (including neurogenic bladder)  1  3/57 (5.26%)  3
Respiratory, thoracic and mediastinal disorders   
Dyspnea (shortness of breath)  1  17/57 (29.82%)  18
Cough  1  9/57 (15.79%)  10
Pulmonary/Upper Respiratory - Other  1  6/57 (10.53%)  7
Hiccoughs  1  6/57 (10.53%)  9
Voice changes/dysarthria  1  3/57 (5.26%)  3
Hemorrhage, pulmonary/upper respiratory - Nose  1  5/57 (8.77%)  5
Skin and subcutaneous tissue disorders   
Rash/desquamation  1  21/57 (36.84%)  30
Dermatology/Skin - Other  1  9/57 (15.79%)  14
Bruising (in absence of Grade 3 or 4 thrombocytopenia)  1  5/57 (8.77%)  5
Rash: hand-foot skin reaction  1  8/57 (14.04%)  10
Flushing  1  5/57 (8.77%)  10
Rash: erythema multiforme  1  5/57 (8.77%)  6
Pruritus/itching  1  4/57 (7.02%)  5
Hair loss/alopecia (scalp or body)  1  4/57 (7.02%)  4
Dry skin  1  3/57 (5.26%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Rachid Baz, M.D.
Organization: H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-8212
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00617591     History of Changes
Other Study ID Numbers: MCC-14986
106095d ( Other Identifier: USF IRB )
RV-MM-PI-107 ( Other Identifier: Celgene Corp. )
07OBCA990185 ( Other Identifier: Ortho Biotech, Inc. )
First Submitted: February 5, 2008
First Posted: February 18, 2008
Results First Submitted: October 25, 2013
Results First Posted: December 17, 2013
Last Update Posted: January 17, 2014