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Study Summary
No. 2008-0089:.......Myeloma......Donna M. Weber......Lymphoma/Myeloma
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Study Summary Title
Study Summary
Number:
2008-0089
Study Title:A Phase I Study of Vorinostat in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma
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Physician New Patient Referral
Name:Donna M. WeberPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Lymphoma/MyelomaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2860
Contact us about clinical trials
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General Information
Disease Group:MyelomaSupported By:Merck & Co., Inc.
Phase of Study:Phase IReturn
Visit:
2 pre-study visits
8 wkly visits for the first 2 cycles
12 biwkly visits for the next 6 cycles
1 EOS visit at 30 days after your last dose
once a month in the extension phase
Treatment
Agents:
Dexamethasone
Lenalidomide
Vorinostat
Home Care:None
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
No hospitalization is needed.
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of the combination of vorinostat, lenalidomide, and dexamethasone that can be
given to patients with MM. The safety of this drug combination will also be
studied.
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Study Objectives / Outcomes
Primary Objective:
To determine the MTD for the combination regimen of vorinostat, lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma.

Secondary Objective:
To assess the safety and tolerability of the combination regimen of vorinostat, lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma.

Exploratory Objectives:
1. To determine the clinical activity for the combination regimen of vorinostat, lenalidomide and dexamethasone.
2. To evaluate the in vivo molecular and biologic effects of vorinostat in combination with dexamethasone and lenalidomide in patients with multiple myeloma through analysis of gene expression.
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Study Status Information
Study Activation / Registration Date:01/02/2009
IRB Review and Approval Date:08/11/2008
Study Type:Phase I
Recruitment Status:Closed
Projected Accrual:44
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patient, or the patient's legal representative, has voluntarily agreed to participate in the study by giving written informed consent.

2) Patient is >/= 18 years of age on the day of signing informed consent.

3) Patient has an established diagnosis of multiple myeloma based on the standard myeloma diagnostic criteria.

4) Patient must have relapsed or refractory multiple myeloma after the most recent treatment regimen as per the European Group for Blood and Marrow Transplantation (EBMT) criteria

5) Patient must have performance status of </= 2 on the ECOG Performance Scale

6) Patient has measurable disease, defined as follows: For secretory multiple myeloma, measurable disease is defined as any quantifiable serum M-protein value and, where applicable, urine light chain of >/= 200 mg/24 hours. For oligo-secretory multiple myeloma, measurable disease is defined as quantifiable light chain paraprotein on serum free light chain assay. For non-secretory multiple myeloma, measurable disease is defined as presence of soft tissue plasmacytoma(s) as determined by clinical examination or radiographic examination such as CT scan and magnetic resonance imaging (MRI), etc.

7) All patients must agree to follow the regional requirements for lenalidomide counseling, pregnancy testing, and birth control; and be willing and able to comply with the regional requirements (for example, periodic pregnancy tests, safety labs, etc).

8) In the US, 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 (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 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.

9) Continued from Inclusion # 8: Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

10) Patient must have adequate organ function as indicated by the following laboratory values: Absolute neutrophil count (ANC) >/= 1,000 /mcL; Platelets >/= 75,000 /mcL; Calculated serum creatinine clearance >/= 50 mL/min; Serum total bilirubin </= 1.5 X ULN; Aspartate aminotransferase (AST) / Serum Glutamic Oxaloacetic Transaminase (SGOT) and Alanine aminotransferase (ALT) / Serum Glutamic Pyruvic Transaminase (SGPT) </= 2.5 X ULN

11) Patient must have received at least one prior standard/experimental anti-myeloma therapy and is at least 3 weeks from prior chemotherapy, radiation therapy, biological therapy, immuno-therapy, major surgery or any other investigational anticancer therapy and has adequately recovered from the toxicities and/or complications of prior therapy unless there is evidence of rapidly progressive disease.

12) Patient is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis.

13) Patient is available for periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study.

Exclusion Criteria:1) Patient had a prior allogeneic bone marrow transplant or plans to undergo autologous or allogeneic bone marrow transplantation within 4 weeks of the initiation of vorinostat administration.

2) Patient had prior treatment with an HDAC inhibitor (e.g., Depsipeptide, MS-275, LAQ-824, 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 be enrolled 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.

3) Patient with concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the combination therapy.

4) Pt has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including, but not limited to the following: active systemic infection, acute or chronic graft versus host disease, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within past 6 months, uncontrolled cardiac arrhythmia, renal failure, psychiatric or social conditions that may interfere with pt compliance,

5) Continued from Exclusion # 4: or any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the pt at unacceptable risk for adverse outcome if he/she were to participate in the study

6) Patient has received intravenous (I.V.) antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug.

7) Patient has known hypersensitivity to lenalidomide, thalidomide, dexamethasone, or components of vorinostat.

8) 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.

9) Patient is pregnant or breast feeding or expecting to conceive or father children within the projected duration of the study.

10) Patient is known to be Human Immunodeficiency Virus (HIV) positive.

11) Patient with known history of Hepatitis B and/or C infection.

12) 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) < 0.1; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician.

13) Patient with plasma cell leukemia defined as the presence of more than 20% plasma cells in the peripheral blood and an absolute plasma cell count of at least 2000 microL.

14) Patient with known history of deep vein thrombosis (DVT) and/or pulmonary embolism (PE).

15) 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.

16) Patient who received lenalidomide within 3 months prior to the first dose.

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Links
Registration Number: NCT00642954
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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