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

April 13, 2015 updated by: Oncotherapeutics

A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide (DVD-R) for Patients With Relapsed/Refractory Multiple Myeloma

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Bakersfield, California, United States, 93309
        • Comprehensive Blood and Cancer Center
      • Fresno, California, United States, 93720
        • Hematology-Oncology Medical Group of Fresno, Inc.
      • Loma Linda, California, United States, 92354
        • Loma Linda University
      • Santa Barbara, California, United States, 93105
        • Santa Barbara Hematology Oncology
      • West Hollywood, California, United States, 90069
        • James R. Berenson, M.D., Inc.
    • Florida
      • Lakeland, Florida, United States, 33805
        • Watson Clinic, LLP, Center for Care and Research
    • New York
      • Cooperstown, New York, United States, 13326
        • Bassett Cancer Institute
      • Johnson City, New York, United States, 13790
        • Broome Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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 Names:
  • Decadron, Velcade, Doxil, Revlimid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Up to 7.5 months (eight 28-day cycles)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to First Response
Time Frame: Up to 7.5 months (eight 28-day cycles)
Up to 7.5 months (eight 28-day cycles)
Time to Best Response
Time Frame: Up to 7.5 months (eight 28-day cycles)
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.
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
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
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Oncotherapeutics

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Celgene Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: James R. Berenson, MD, James R. Berenson, MD, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 7, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 12, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 4, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 13, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RV-MM-PI-0533

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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