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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2008 by Weill Medical College of Cornell University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00538824
First received: October 2, 2007
Last updated: December 2, 2008
Last verified: December 2008
  Purpose

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.

Condition Intervention Phase
Multiple Myeloma
Drug: dexamethasone
Drug: thalidomide
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Dexamethasone (DECADRON®), Thalidomide (THALOMID®), and Lenalidomide (REVLIMID®) for Subjects With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • effect of drug combination on multiple myeloma [ Time Frame: duration of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: December 2007
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    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*

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00538824

Locations
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Celgene Corporation
Investigators
Principal Investigator: Ruben Niesvizky, MD Weill Medical College of Cornell University
  More Information

Additional Information:
No publications provided

Responsible Party: Ruben Niesvizky, MD, Weill Cornell Medical College
ClinicalTrials.gov Identifier: NCT00538824     History of Changes
Other Study ID Numbers: 0708009381, RV-MM-PI-0132
Study First Received: October 2, 2007
Last Updated: December 2, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by Weill Medical College of Cornell University:
myeloma
relapsed or refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 22, 2014