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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

Phase 1
18 Years
Open (Enrolling)
Multiple Myeloma

Thank you

Trial Information

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

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

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:

Standard Criteria

Major criteria:

1. Plasmacytomas on tissue biopsy.

2. Bone marrow plasmacytosis (>30% plasma cells). 3 Monoclonal immunoglobulin spike on
serum electrophoresis immunoglobulin G (IgG) >3.5 g/dL or immunoglobulin A (IgA) >2.0
g/dL; kappa or lambda light chain excretion >1 g/day on 24 hour urine protein

Minor criteria:

1. Bone marrow plasmacytosis (10 to 30% plasma cells)

2. Monoclonal immunoglobulin present but of lesser magnitude than given under major

3. Lytic bone lesions

4. Normal IgM <50 mg/dL, IgA <100 mg/dL or IgG <600 mg/dL.

Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:

- Any two of the major criteria.

- Major criterion 1 plus minor criterion b, c or d.

- Major criterion 3 plus minor criterion a or c.

- Minor criteria a, b and c or a, b and d.

- 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 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. See Appendix IX: Risks of Fetal Exposure, Pregnancy
Testing Guidelines and Acceptable Birth Control Methods,.

- 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. (Appendix II, Section 8.2)

- Subject must be able to adhere to the study visit schedule and other protocol

- 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 ASA may use warfarin or low molecular weight heparin).

Exclusion Criteria:

A female of childbearing potential is a sexually mature woman who: 1) has not undergone a
hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at
least 24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months).

- 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.

- AST (SGOT and ALT (SGPT) > 2 x 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 (see section 8.4), 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of vorinostat in combination with lenalidomide, bortezomib, and dexamethasone.

Outcome Time Frame:

Every 3 weeks

Safety Issue:


Principal Investigator

Jonathan Kaufman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Emory University


United States: Institutional Review Board

Study ID:




Start Date:

January 2010

Completion Date:

June 2013

Related Keywords:

  • Multiple Myeloma
  • Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



University of Texas, M.D. Anderson Cancer Center Houston, Texas  77030
Emory University Winship Cancer Institute Atlanta, Georgia  30322