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Study Summary
No. 2008-0794:.......Myeloma......Jatin J. Shah......Lymphoma/Myeloma
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Study Summary Title
Study Summary
Number:
2008-0794
Study 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
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Physician New Patient Referral
Name:Jatin J. ShahPatients 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:Celgene
Merck
Phase of Study:Phase IReturn
Visit:
Every 3 weeks for routine 8 cycles then every 4 weeks as long as responding to
treatment so it could be as few as 2 and unlimited as long as on therapy.

Treatment
Agents:
Bortezomib
Dexamethasone
Revlimid
Vorinostat
Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
NA
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of Zolinza (vorinostat) that can be given in combination with Velcade
(bortezomib), Revlimid (lenalidomide), and dexamethasone to patients with MM.
The safety of this drug combination will also be studied.
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Study Objectives / Outcomes
The primary objective of the Phase I study is to determine the maxium tolerated dose (MTD) of the combination of escalating doses of vorinostat and lenalidomide with bortezomib and dexamethasone (RVD) in newly diagnosed multiple myeloma patients. The secondary objectives of this study are to evaluate the overall response, the complete remission (CR) + near complete remission (nCR) rate at the end of 4 and 8 cycles, very good partial remission (VGPR) or better rate at the end of 4 and 8 cycles, the time to progression, duration of response, time to next therapy, progression free and overall survival and the tolerability and toxicity of the combination of vorinostat with RVD in patients with newly diagnosed multiple myeloma. For patients who elect to go on to stem cell transplant, exploratory endpoints will also include stem cell harvesting data (number of CD34+ cells and days of harvesting) and engraftment parameters.
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Study Status Information
Study Activation / Registration Date:04/23/2010
IRB Review and Approval Date:04/23/2010
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Terminated
Projected Accrual:30
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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) Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria (Listed Below).

2) IMF 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 of the following); [C] Calcium elevation in the blood S. Calcium > 10.5 mg/l or upper limit of normal, [R] Renal insufficiency Serum (S.) Creatinine >2 mg/dl, [A] Anemia Hemoglobin < 10 mg/dl or 2 g < normal, [B] Lytic bone lesions or osteoporosis.

3) 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 160mg of dexamethasone in a 2 week period), Bisphosphonates are permitted.

4) 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 has passed since the last date of therapy.

5) 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.

6) 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 starting 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.

7) # 6 continued: 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.

8) Age >/= 18 years at the time of signing Informed Consent.

9) All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment.

10) Subject has a Karnofsky performance status of >/= 60.

11) Subject must be able to adhere to the study visit schedule and other protocol requirements.

12) All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

13) Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin may use warfarin or low molecular weight heparin).

Exclusion Criteria:1) Patient has >/= Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment.

2) Renal insufficiency (serum creatinine levels > 2.5 mg/dL).

3) Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count >/= 50,000 cells/mm3).

4) Subjects with an absolute neutrophil count (ANC) < 1000 cells/mm3. Growth factors may not be used to meet ANC eligibility criteria.

5) Subjects with a hemoglobin < 8.0 g/dL.

6) AST (SGOT and ALT (SGPT) >/= 2 x ULN.

7) 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.

8) Clinically relevant active infection requiring intravenous antibiotics.

9) Serious co-morbid medical conditions such as chronic obstructive or chronic restrictive pulmonary disease, and cirrhosis.

10) 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.

11) Patients with a prior malignancy (within the last 3 years), however patients with adequately treated basel cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer are eligible. Patients with a prior malignancy who have an expected survival from this prior malignancy of greater than 90% at 5 years may also be eligible

12) Female subject is pregnant or breast-feeding.

13) Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

14) Uncontrolled diabetes mellitus (Fasting Blood Sugar > 400 despite medical treatment).

15) Hypersensitivity to acyclovir or similar anti-viral drug.

16) Known history of POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).

17) Known HIV infection.

18) Known active hepatitis B or C viral infection.

19) Patients taking valproic acid for epilepsy will not be allowed to enroll on this study prior to a 30 day washout period. Patients with epilepsy should take any HDAC inhibitor or HDAC like inhibitor other than calprioic acid. If no other alternative is available, patients taking valprioc acid for epilepsy may enroll after a 30 day washout period.

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Links
Registration Number: NCT01038388
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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