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Trial record 36 of 372 for:    LENALIDOMIDE AND Dexamethasone

A Study of the Combination Vorinostat With Lenalidomide, Bortezomib and Dexamethasone for Patients With Newly Diagnosed 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. Identifier: NCT01038388
Recruitment Status : Active, not recruiting
First Posted : December 24, 2009
Last Update Posted : February 18, 2019
Merck Sharp & Dohme Corp.
Celgene Corporation
Information provided by (Responsible Party):
Jonathan Kaufman, Emory University

Brief Summary:
The purpose of the study is to evaluate the clinical effectiveness and side effects of the vorinostat, bortezomib, lenalidomide, and dexamethasone investigational combination.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Bortezomib Drug: Lenalidomide Drug: Dexamethasone Drug: Vorinostat Phase 1

Detailed Description:

The purpose of the study is to evaluate the clinical effectiveness and side effects of the vorinostat, bortezomib, lenalidomide, and dexamethasone investigational combination.

All of these drugs - vorinostat, bortezomib, lenalidomide and dexamethasone, are approved by the FDA (U.S. Food and Drug Administration). They have not been approved in this combination for use in your type of cancer or any other type of cancer. Vorinostat is approved for treatment of patients with a different type of cancer (Cutaneous T-Cell Lymphoma). Bortezomib is currently approved for the treatment of multiple myeloma. Lenalidomide is currently approved for the treatment of certain types of myelodysplastic syndrome (another form of cancer affecting the blood) and for use with dexamethasone for patients with multiple myeloma who have received at least one prior therapy. Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial Evaluating the Safety and Efficacy of Vorinostat (Zolinza ®) + RVD (Lenalidomide {Revlimid ®} + Bortezomib {Velcade ®} + Dexamethasone) for Patients With Newly Diagnosed Multiple Myeloma
Actual Study Start Date : January 15, 2010
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Arm Intervention/treatment
Experimental: Bortezomib, lenalidomide, dexamethasone, vorinostat

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11; lenalidomide by mouth once a day on days 1-14; dexamethasone by mouth once a day on days 1, 2, 4, 5, 8, 9, 11, and 12; and vorinostat by mouth on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After 8 courses, patients may receive maintenance therapy comprising lenalidomide by mouth once a day on days 1-21, dexamethasone by mouth once a day on days 1, 2, 8, and 9, and bortezomib IV over 3-5 seconds or subcutaneously on days 1 and 8. Courses may repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib
1.3mg/m² given IV or subcutaneously
Other Name: Velcade

Drug: Lenalidomide
25 mg given PO
Other Name: Revlimid

Drug: Dexamethasone
20 mg given PO
Other Name: Decadron

Drug: Vorinostat
100, 200, or 300 mg given PO
Other Name: Zolinza

Primary Outcome Measures :
  1. To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of vorinostat in combination with lenalidomide, bortezomib, and dexamethasone. [ Time Frame: Every 3 weeks ]

Secondary Outcome Measures :
  1. Efficacy by standard myeloma measurements (SPEP, UPEP [urine protein electrophoresis], bone marrow) [ Time Frame: Every 3 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Multiple Myeloma Diagnosis: Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria (ALL 3 REQUIRED):

    1. Monoclonal plasma cells in the bone marrow > 10% and/or presence of a biopsy-proven plasmacytoma.
    2. Monoclonal protein present in the serum and/or urine.
    3. Myeloma-related organ dysfunction (1 or more).

      • [C] Calcium elevation in the blood S. Calcium >10.5 mg/l or upper limit of normal{}.
      • [R] Renal insufficiency S. Creatinine > 2 mg/dl{}.
      • [A] Anemia Hemoglobin < 10 g/dl or 2 g < normal{}.
      • [B] Lytic bone lesions or osteoporosis.
  • Patient must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma.

    • Prior treatment of hypercalcemia or spinal cord compression with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period).
    • Bisphosphonates are permitted
  • Patients treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, are eligible. One week must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and one week have passed since the last date of therapy.
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international unit (mIU)/mL 10 - 14 days prior to therapy and repeated again within 24 hours of prescribing lenalidomide 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 28 days 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 a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
  • Age ≥ 18 years at the time of signing Informed Consent.
  • All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment.
  • Subject has a Karnofsky performance status of ≥ 60.
  • Subject must be able to adhere to the study visit schedule and other protocol requirements.
  • All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
  • 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:

  • Patient has ≥ Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment.
  • Renal insufficiency (serum creatinine levels > 2.5 mg/dL).
  • Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count ≥ 50,000 cells/mm³).
  • Subjects with an absolute neutrophil count (ANC) < 1000 cells/mm³. Growth factors may not be used to meet ANC eligibility criteria.
  • Subjects with a hemoglobin < 8.0 g/dL.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN).
  • Concomitant therapy medications that include corticosteroids (except as indicated in inclusion criteria).
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic 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.
  • Clinically relevant active infection requiring intravenous antibiotics.
  • Serious co-morbid medical conditions such as chronic obstructive or chronic restrictive pulmonary disease, and cirrhosis.
  • Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study.
  • Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or if the expected survival from other malignancy is greater than 90% at 5 years.
  • Female subject is pregnant or breast-feeding.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Uncontrolled diabetes mellitus (Fasting Blood Sugar > 400 despite medical treatment).
  • Hypersensitivity to acyclovir or similar anti-viral drug.
  • Known history of POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).
  • Known HIV infection .
  • Known active hepatitis B or C viral infection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01038388

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United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Merck Sharp & Dohme Corp.
Celgene Corporation
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Principal Investigator: Jonathan Kaufman, MD Emory University

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Responsible Party: Jonathan Kaufman, MD, Emory University Identifier: NCT01038388     History of Changes
Other Study ID Numbers: IRB00017528
1591 ( Other Identifier: Other )
RV-MM-PI-0420 ( Other Identifier: Winship Cancer Institute )
First Posted: December 24, 2009    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jonathan Kaufman, Emory University:
Multiple Myeloma
Additional relevant MeSH terms:
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Dexamethasone acetate
BB 1101
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal