Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01160484
Recruitment Status : Completed
First Posted : July 12, 2010
Results First Posted : April 21, 2014
Last Update Posted : May 4, 2015
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Oncotherapeutics

Tracking Information
First Submitted Date  ICMJE July 7, 2010
First Posted Date  ICMJE July 12, 2010
Results First Submitted Date  ICMJE January 10, 2014
Results First Posted Date  ICMJE April 21, 2014
Last Update Posted Date May 4, 2015
Study Start Date  ICMJE September 2009
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 24, 2014)
International Myeloma Working Group (IMWG) Response Criteria [ Time Frame: Up to 7.5 months (eight 28-day cycles) ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 9, 2010)
IMWG Response Criteria [ Time Frame: up to 32 weeks ]
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 CR, VGPR, PR, or MR, then assessment of disease response is to be performed 4 weeks later to confirm the response.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2014)
  • Time to First Response [ Time Frame: Up to 7.5 months (eight 28-day cycles) ]
  • Time to Best Response [ Time Frame: Up to 7.5 months (eight 28-day cycles) ]
  • Duration of Response [ Time Frame: First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death. ]
  • Time to Progression [ Time Frame: Time from the start of treatment to progressive disease ]
  • Progression-free Survival [ Time Frame: Time from the start of treatment to progressive disease or until death ]
  • Follow-up Time [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2010)
  • Adverse Events [ Time Frame: up to 36 weeks ]
    Occurrence of adverse events throughout the study using CTCAE ctriteria version 3.0.
  • Clinical laboratory [ Time Frame: up to 32 weeks ]
    • Hematology (hematocrit, hemoglobin, RBC count, WBC count, with differential, platelet count.
    • Serum electrolyte and glucose panel (sodium, potassium, chloride, calcium, and glucose).
    • Serum beta human chorionic gonadotropin pregnancy test for women of child-bearing potential
    • Chemistry [BUN, serum creatinine, bilirubin (total), alkaline phosphatase, total protein, albumin, AST (SGOT), ALT (SGPT)]
    • Amylase
  • Vital signs [ Time Frame: up to 32 weeks ]
    Pulse, blood pressure, respiratory rate, and body temperature
  • Medical history [ Time Frame: up to 32 weeks ]
  • Physical Examination [ Time Frame: up to 32 weeks ]
    Body weight measurements
  • Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: up to 32 weeks ]
    SCORE DESCRIPTION 0 Fully active, able to carry on all pre-disease performance without restriction.
    1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.
    2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
    3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
    4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
    5. Dead.
  • Concomitant medication usage [ Time Frame: up to 32 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide for Relapsed/Refractory Multiple Myeloma
Official Title  ICMJE A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide (DVD-R) for Patients With Relapsed/Refractory Multiple Myeloma
Brief Summary This is a phase II, multicenter, open label, nonrandomized study to evaluate the efficacy and safety of lenalidomide at a dose of 10 mg/dose in combination with bortezomib at 1.0 mg/m2/dose, pegylated liposomal doxorubicin (PLD) at 4.0 mg/m2/dose, and intravenous (IV) dexamethasone at 40 mg/dose in adult patients with relapsed/refractory multiple myeloma (MM). The study consists of a screening period, followed by up to eight 28 day open label treatment cycles, a final assessment to occur 28 days after the end of the last treatment cycle, and a follow-up period.
Detailed Description Studies have shown that combinations of PLD and bortezomib have striking synergy in preclinical studies and impressive response rates (73 & 89%) in early clinical trials for MM patients with relapsed/refractory disease as well as first-line therapy. In addition, the efficacy of PLD with bortezomib in anthracycline-insensitive patients has been greater than single-agent bortezomib when comparing across studies. The immunomodulatory drugs, thalidomide and lenalidomide, target the tumor cell microenvironment, are antiangiogenic, have an immune activation effect and also exert a direct cytotoxic effect on myeloma cells. A phase 1 clinical study by our group also demonstrated that low dose PLD, administered at a more frequent dosing schedule, in combination with bortezomib, and dexamethasone (DVD regimen) is well tolerated and associated with high response rates and durable responses. In this phase II prospective trial, we will evaluate this regimen and show that this change enhances the DVD-R regimen's safety and efficacy for patients with relapsed/refractory MM.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Drug: DVD-R
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.
Other Name: Decadron, Velcade, Doxil, Revlimid
Study Arms  ICMJE Experimental: DVD-R single arm

Dose schematic of Dexamethasone + Bortezomib + Pegylated Liposomal Doxorubicin + Lenalidomide (DVD-R) Therapy:

Dexamethasone*- 40 mg IV Bortezomib**- 1.0 mg/m2 IV Push Pegylated Liposomal Doxorubicin*- 4.0 mg/m2 IV Lenalidomide***- 10 mg PO

Per 28 Day Cycle

  • Intravenous infusion (IV) Days 1, 4, 8 and 11 ** Intravenous push (IVP) Days 1, 4, 8 and 11 *** Per Orem (PO) Days 1-14
Intervention: Drug: DVD-R
Publications * Berenson JR, Yellin O, Kazamel T, Hilger JD, Chen CS, Cartmell A, Woliver T, Flam M, Bravin E, Nassir Y, Vescio R, Swift RA. A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma. Leukemia. 2012 Jul;26(7):1675-80. doi: 10.1038/leu.2012.51. Epub 2012 Feb 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 9, 2010)
40
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2012
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Has a diagnosis of multiple myeloma (MM) based on standard criteria (Durie 1986)
  2. Currently has MM with measurable disease (serum m protein > 1.0g/dl and/or 24 hr urine m protein > 200mg/24 hr)
  3. Currently has progressive MM that has relapsed or is refractory
  4. Voluntarily signed an informed consent
  5. Age 18 years
  6. Eastern Cooperative Oncology Group (ECOG) performance < 2
  7. Life-expectancy > 3 months
  8. Laboratory test results within these ranges:

    • Absolute neutrophil count (ANC) 1.5 x 109/L; if the bone marrow is extensively infiltrated (> 70% plasma cells) then 1.0 x 109/L
    • Platelet count 75 x 109/L; if the bone marrow is extensively infiltrated (> 70% plasma cells) then 50 x 109/L
    • Hg > 8 g/dL
    • Calculated or measured creatinine clearance > 30 mL/minute.
    • Total bilirubin 2.0 x upper limit of normal (ULN)
    • Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) 3 x ULN or 5 x ULN if hepatic metastases are present
    • Serum potassium within the normal range
  9. Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
  10. Registered into the mandatory RevAssist® program, willing and able to comply with the requirements of RevAssist®.
  11. Females of childbearing potential must have a negative serum or urine pregnancy test and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control.
  12. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight heparin)

Exclusion Criteria:

  1. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome
  2. Plasma cell leukemia
  3. Grade 2 peripheral neuropathy within 14 days before enrollment
  4. Impaired cardiac function or clinically significant cardiac diseases, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class II or greater heart failure, Uncontrolled angina, clinically significant pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or Multigated acquisition(MUGA) scan evidence of left ventricular ejection fraction (LVEF) below institutional normal within 28 days prior to enrollment, electrocardiographic (ECG) evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  5. Severe hypercalcemia, i.e., serum calcium 12 mg/dL (3.0 mmol/L) corrected for albumin
  6. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  7. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  8. Undergone major surgery within 28 days prior enrollment or has not recovered from side effects of such therapy (Kyphoplasty is not considered to be a major surgery; however, the investigator is to discuss enrollment of a patient with a recent history of kyphoplasty with the medical monitor).
  9. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide)
  10. Received the following prior therapy:

    • Chemotherapy within 3 weeks of enrollment (6 wks for nitrosoureas)
    • Corticosteroids (>10 mg/day prednisone or equivalent) within 3 weeks of enrollment
    • Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic trioxide or bortezomib within 21 days before enrollment
    • Radiation therapy within 28 days before enrollment, except localized radiation therapy
    • Use of any other experimental drug or therapy within 28 days of enrollment
  11. Known hypersensitivity to compounds of similar to thalidomide, doxorubicin, bortezomib, boron or mannitol.
  12. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  13. Concurrent use of other anti-cancer agents or treatments
  14. Known positivity for human immunodeficiency virus (HIV) or hepatitis B or C; baseline testing for HIV and hepatitis B or C is not required
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01160484
Other Study ID Numbers  ICMJE RV-MM-PI-0533
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Oncotherapeutics
Study Sponsor  ICMJE Oncotherapeutics
Collaborators  ICMJE Celgene Corporation
Investigators  ICMJE
Principal Investigator: James R. Berenson, MD James R. Berenson, MD, Inc.
PRS Account Oncotherapeutics
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP