A Study of the Combination Vorinostat With Lenalidomide, Bortezomib and Dexamethasone for Patients With Newly Diagnosed Multiple Myeloma

NCT01038388 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: IRB000175281591RV-MM-PI-0420
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

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

  Every 3 weeks

Secondary Outcomes (1)

• Efficacy by standard myeloma measurements (SPEP, UPEP [urine protein electrophoresis], bone marrow)

  Every 3 weeks

Study Arms (1)

Bortezomib, lenalidomide, dexamethasone, vorinostat

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Vorinostat

Interventions

Bortezomib DRUG

1.3mg/m² given IV or subcutaneously

Also known as: Velcade

Bortezomib, lenalidomide, dexamethasone, vorinostat

Lenalidomide DRUG

25 mg given PO

Also known as: Revlimid

Bortezomib, lenalidomide, dexamethasone, vorinostat

Dexamethasone DRUG

20 mg given PO

Also known as: Decadron

Bortezomib, lenalidomide, dexamethasone, vorinostat

Vorinostat DRUG

100, 200, or 300 mg given PO

Also known as: Zolinza

Bortezomib, lenalidomide, dexamethasone, vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Monoclonal plasma cells in the bone marrow \> 10% and/or presence of a biopsy-proven plasmacytoma.
• Monoclonal protein present in the serum and/or urine.
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Emory University: lead
• Merck Sharp & Dohme LLC: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Lenalidomide; Dexamethasone; Calcium Dobesilate; Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids

Study Officials

• Jonathan Kaufman, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 7, 2009
• First Posted: December 24, 2009
• Study Start: January 15, 2010
• Primary Completion: August 5, 2021
• Study Completion: August 5, 2021
• Last Updated: November 3, 2021

Record last verified: 2021-11

Locations

US (1)