Phase II Study of Dexamethasone, Thalidomide and Lenalidomide for Subjects With Relapsed or Refractory Multiple Myeloma (DexTR)

May 31, 2018 updated by: Weill Medical College of Cornell University

A Phase II Study of Dexamethasone (DECADRON®), Thalidomide (THALOMID®), and Lenalidomide (REVLIMID®) for Subjects With Relapsed or Refractory Multiple Myeloma

Study Objectives

  1. To evaluate the efficacy of the combination of dexamethasone (Decadron®), thalidomide (Thalomid®), and lenalidomide (Revlimid®) as therapy for patients with relapsed or refractory multiple myeloma (MM) who have failed prior treatment with both lenalidomide and thalidomide when used as monotherapies.
  2. To evaluate the safety of the combination of lenalidomide, dexamethasone, and thalidomide as a therapy for patients with relapsed or refractory multiple myeloma.

Study Overview

Status

Status

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

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

This phase II study is a treatment program for patients with relapsed or refractory multiple myeloma who have had prior treatment with both thalidomide and lenalidomide in separate regimens each used as a single agent or in combination with corticosteroids. Up to 45 patients will be enrolled. Patients who sign informed consent form and RevAssist® and S.T.E.P.S® patient agreement form and fulfill all eligibility criteria will be enrolled.

DexTR therapy:

Cycles 1-4

  • Dexamethasone (40mg ) will be given on days 1-4, 9-12, 17-20 of a 28-day cycle.
  • Thalidomide will be given 50mg daily on days 1-7, thereafter 100mg daily on days 8-28 of the first 28-day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 of each subsequent cycle.
  • Lenalidomide will be given 25mg daily for days 1-21 of each 28 day cycle.
  • Prophylactic medications, such as medications for thrombosis risk, will be given.

After completing 4 cycles:

  • Patients who demonstrate disease progression at any time will be taken off study.
  • Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for > 2 cycles will be transitioned to maintenance therapy.
  • Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for >2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.

Maintenance therapy:

Maintenance therapy will consist of:

  • Dexamethasone 20mg weekly days 1, 8, 15, 22 out of a 28 day cycle)

  • Lenalidomide 25 mg/daily days 1 - 21 out of a 28 day cycle. 15mg/daily on days 1-21 of a 28 day cycle of lenalidomide will be given to patients with a creatinine clearance of < 40cc/min*

    • Patients who finished induction therapy with DexTR at a reduced dose of lenalidomide will start maintenance therapy at the same dose of lenalidomide on which they ended induction therapy. For patients with a creatinine clearance of < 40cc / minute, the lenalidomide dose will be the lower of their last induction therapy dose or 15mg daily on days 1 - 21 out of a 28 day cycle.

Serial clinic visits and laboratory measurements will be performed to monitor for treatment response. Those patients who demonstrate progression of disease at any point during DexTR therapy will be taken off study.

At the end of every cycle (which may coincide with day 1 of the new cycle), response and toxicity will be evaluated. During cycle 1, patients will have lab work done weekly (CBC with differential and blood electrolytes). All patients will remain on study until disease progression or side effects become excessive. Patients who achieve a stable plateau and are on maintenance therapy as defined above may be taken off study if eligible to proceed to high dose chemotherapy and autologous stem cell transplantation.

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.
5

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
    • New York
      • New York, New York, United States, 10021
        • Weill Medical College of Cornell University

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subject must voluntarily sign and understand written informed consent.
  • Age > 18 years at the time of signing the consent form.
  • Histologically confirmed Salmon-Durie stage II or III MM. Stage I MM patients will be eligible if they display poor prognostic factors (ß2M ≥5.5 mg/L, plasma cell proliferation index ≥5%, albumin of less then 3.0, and unfavorable cytogenetics).
  • Relapsed or refractory myeloma as defined by Appendix II, table 1, progression of disease either after prior therapy or lack of response to currently used therapy.
  • Prior treatment with prior lenalidomide and thalidomide as single agents or in combination with dexamethasone, but not in combination with each other.
  • No anti-myeloma therapy within 14 days prior to initiation of study treatment. Patients may be receiving adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care.
  • Measurable disease as defined by > 1.0 g/dL serum monoclonal protein, >0.1 g/dL serum free light chains, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
  • Karnofsky performance status ≥70% (>60% if due to bony involvement of myeloma.
  • All study participants must be registered into the mandatory RevAssist® and S.T.E.P.S.® programs, and be willing and able to comply with the requirements of the RevAssist® and S.T.E.P.S.® programs.
  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide and thalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
  • Able to take aspirin daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
  • Life expectancy ≥ 3 months

  • Subjects must meet the following laboratory parameters:

    • Absolute neutrophil count (ANC) ≥1000 cells/mm3 (1.0 x 109/L)
    • Platelets count ≥ 75,000/mm3 (75 x 109/L)
    • Serum SGOT/AST <3.0 x upper limits of normal (ULN)
    • Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
    • Serum creatinine <2.5 mg/dL (221 µmol/L)
    • Serum total bilirubin <2.0 mg/dL (34 µmol/L)

Exclusion Criteria:

  • Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine).
  • Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ≥ 5 years.
  • Myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • Pregnant or lactating females are ineligible.
  • Given the potential of the study drugs to trigger or worsen HIV viremia and the incidence of opportunistic infections inpatients infected with the HIV virus, HIV-1 or HIV-2 positive patients will be excluded. The interactions of HAART with study drugs have not been determined.
  • Active hepatitis B or hepatitis C infection.
  • Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
  • Any coexisting medical problem or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial.
  • Known hypersensitivity to dexamethasone, lenalidomide, or thalidomide.
  • History of thromboembolic event within the past 6 months prior to enrollment.

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: DexTR (all patients)
All patients were treated with the DexTR (dexamethasone / thalidomide, lenalidomide (Revlimid®)), which consisted of lenalidomide 25mg/day during days 1-21, dexamethasone 40mg/day on days 1-4, 9-12, and 17-20, and thalidomide 50mg/day for the first 7 days, followed by 100mg/day for all subsequent days, for a total of 4 cycles of 28 days each.
Drug: dexamethasone

Cycles 1-4 • Dexamethasone (40mg ) will be given on days 1-4, 9-12, 17-20 of a 28-day cycle.

After completing 4 cycles:

  • Patients who demonstrate disease progression at any time will be taken off study.
  • Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for > 2 cycles will be transitioned to maintenance therapy.
  • Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for >2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.

Maintenance therapy will consist of:

• Dexamethasone 20mg weekly days 1, 8, 15, 22 out of a 28 day cycle)

Drug: thalidomide

Cycles 1-4

• Thalidomide will be given 50mg daily on days 1-7, thereafter 100mg daily on days 8-28 of the first 28-day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 of each subsequent cycle.

After completing 4 cycles:

  • Patients who demonstrate disease progression at any time will be taken off study.
  • Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for > 2 cycles will be transitioned to maintenance therapy.
  • Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for >2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.
Drug: lenalidomide

Cycles 1-4 • Lenalidomide will be given 25mg daily for days 1-21 of each 28 day cycle.

After completing 4 cycles:

  • Patients who demonstrate disease progression at any time will be taken off study.
  • Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for > 2 cycles will be transitioned to maintenance therapy.
  • Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for >2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.

Maintenance therapy will consist of:

• Lenalidomide 25 mg/daily days 1 - 21 out of a 28 day cycle. 15mg/daily on days 1-21 of a 28 day cycle of lenalidomide will be given to patients with a creatinine clearance of < 40cc/min*

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
Effect of Drug Combination on Multiple Myeloma
Time Frame: The best response for all patients at any point were assessed for patients that were treated on study, from start of treatment up to 20 weeks
The maximum response for all patients that were treated on study. Maximum response was assessed using the International myeloma working group (IMWG) guidelines for response. http://imwg.myeloma.org/international-myeloma-working-group-imwg-uniform-response-criteria-for-multiple-myeloma/
The best response for all patients at any point were assessed for patients that were treated on study, from start of treatment up to 20 weeks

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.
Weill Medical College of Cornell University

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

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: Ruben Niesvizky, MD, Weill Medical College of Cornell University

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 (Actual)

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.
December 1, 2007

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.
September 22, 2010

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 22, 2010

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).
October 2, 2007

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.
October 2, 2007

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.
October 3, 2007

Study Record Updates

Last Update Posted (Actual)

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.
June 6, 2018

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.
May 31, 2018

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.
May 1, 2018

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.
  • 0708009381
  • RV-MM-PI-0132

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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