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Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant for Multiple Myeloma

Phase 2
18 Years
Open (Enrolling)
Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

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Trial Information

Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant for Multiple Myeloma


I. Evaluate the toxicity of the use of vorinostat and bortezomib as maintenance therapy
after autologous transplant.


I. Evaluate the median time to disease progression. II. Evaluate survival.

OUTLINE: Patients receive bortezomib intravenously (IV) on days 2 and 5 and vorinostat
orally (PO) once daily (QD) on days 1-14. Treatment repeats every 28 days for 12 courses in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Any autologous patient who underwent high dose melphalan (>= 140 mg/m^2) therapy or
peripheral blood stem cell (PBSC) rescue for any stage of multiple myeloma and did
not participate in another clinical transplant trial whose primary endpoint is also
evaluating long-term, disease-free survival, or survival

- Platelet count (transfusion independent) > 75,000 cells/mm^3 and absolute granulocyte
count > 1500 cells/mm^3 for 5 calendar days after recovery from high dose therapy

- Consenting for study between 30 days to 120 days after transplant

- Female patient of childbearing potential has a negative serum pregnancy test beta-hCG
within 72 hours prior to receiving the first dose of vorinostat

- Female patient is either post-menopausal, free from menses for >= 2 years, surgically
sterilized, or willing to use 2 adequate barrier methods of contraception to prevent
pregnancy or agrees to abstain from heterosexual activity throughout the treatment on
study, starting with visit 1 and for 3 months afterward

- Male patient agrees to use an adequate method of contraception for the duration of
the treatment on study and for 3 months afterward

Exclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status >= 2

- A left ventricular ejection fraction less than 45% pre-transplant

- Congestive heart disease with transplant, history of myocardial infarction (MI),
history of coronary artery disease, or prolonged QTC

- Total bilirubin greater than 2 mg/ml (unless history of Gilbert's disease)

- Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase
(SGPT) > 2.5 x upper limit of normal (ULN)

- Creatinine clearance < 20 ml/minute, calculated by Cockroft-Gault formula or measured

- Cannot give informed consent

- Untreated systemic infection

- Poorly-controlled diabetes mellitus (DM)

- >= grade 3 peripheral neuropathy

- Prior history of human immunodeficiency virus (HIV) positivity with pre-transplant
evaluation or known history of hepatitis B or C

- Previous history of hypersensitivity to Bortezomib, boron, or mannitol; known
hypersensitivity to the components of study drug or its analogs

- Require therapeutic anticoagulation treatment, especially with coumadin

- Potassium (K) and magnesium (Mg) < normal limits

- Patient who has had chemotherapy, radiotherapy, or biological therapy, within 30 days
(42 days for nitrosoureas or mitomycin C) prior to initial dosing with study drug(s)
or who has not recovered from adverse events due to agents administered more than 30
days earlier; patients who have received localized consolidation radiation to bone
only less than 30 days prior to study entry are allowed

- Patient is currently participating or has participated in a study with an
investigational compound or device within 30 days of initial dosing with study drugs

- Patient had prior treatment with an histone deacetylase inhibitor (HDAC) inhibitor
(e.g., romidespin [depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101],
LBH589, MGCD0103, CRA024781, etc.)

- Patients who have received compounds with HDAC inhibitor-like activity, such as
valproic acid, as anti-tumor therapy should not enroll in this study

- Patients who have received such compounds for other indications, e.g. valproic acid
for epilepsy, may enroll after a 30-day washout period

- History of central nervous system (CNS) disease

- Symptomatic ascites or pleural effusions

- Patient has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial

- Patient is, at the time of signing informed consent, a regular user (including
"recreational use") of any illicit drugs, substance abuse or had a recent history
(within the last year) of drug or alcohol abuse

- Patient is pregnant or breast-feeding, or expecting to conceive or father children
within the projected duration of the study

- Patient with a history of a prior malignancy with the exception of cervical
intraepithelial neoplasia; non-melanoma skin cancer; adequately treated localized
prostate carcinoma with prostate-specific antigen (PSA) < 1.0; or who has undergone
potentially curative therapy with no evidence of disease for five years, and/or who
is deemed at low risk for recurrence by his/her treating physician

- Patient has a history or current evidence of any condition, therapy, or lab
abnormality that might confound the results of the study, interfere with the
patient's participation for the full duration of the study or is not in the best
interest of the patient to participate

- Patient has a history of a gastrointestinal surgery or other procedures that might,
in the opinion of the investigator, interfere with the absorption or swallowing of
the study drugs

Type of Study:


Study Design:

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

Outcome Measure:

Toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

Outcome Description:

The first three months of therapy will be used as the time period in which toxicity will be evaluated and stopping rules for unacceptable toxicity will be implemented. Patients who received only one autologous transplant and patients who received two autologous transplants will be analyzed separately for toxicity. The withdrawal rate will be examined after every 10th enrolled patient becomes evaluable in each group. Sufficient evidence will be taken to be a lower limit to the corresponding one-side 80% confidence interval that exceeds 15%

Outcome Time Frame:

The first three months of therapy

Safety Issue:


Principal Investigator

Leona Holmberg

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Institutional Review Board

Study ID:




Start Date:

February 2009

Completion Date:

Related Keywords:

  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109