- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00361088
A Combination of Zarnestra With Velcade for Patients With Relapsed Multiple Myeloma
A Dose Escalation of Zarnestra (R115777) Combined With Velcade® (PS-341) in Patients With Relapsed Multiple Myeloma
Study Overview
Detailed Description
In Phase I, patients will receive intravenous PS-341 (Velcade) and 3 different dose levels of oral R115777 (Zarnestra). Dose Limiting Toxicity (DLT) will be determined over a period of one cycle and dose escalation to the next level will not occur until all patients projected at each level complete one cycle of therapy. Once DLT is determined, patients in Phase I and all patients enrolled for the phase II component will be treated at the maximum tolerated dose (MTD) to complete 8 cycles of therapy. Treatment will continue beyond 8 cycles if there is evidence of continued response. The study regimen will consist of two weeks of treatment followed by one week off for a total cycle duration of three weeks. If disease stabilization occurs (noted on 2 consecutive cycles) after the standard 8 cycles are given, treatment will be discontinued.
Patients are to be monitored for adverse events throughout the treatment phases and for a minimum of 30 days after their last dose of drugs. Follow up will include history and physical exam with laboratory evaluation at least every 3 months. Laboratories will include CMP, CBC, SPEP, UPEP, and quantitative immunoglobulins. A skeletal survey will be performed at least every 6 months.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center & Research Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Voluntary written informed consent
- Female subject is either post-menopausal/surgically sterilized or willing to use an acceptable method of birth control for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
Diagnosis of stage II or III multiple myeloma and have relapsed after at least one prior therapies confirmed by the presence of:
- A new lytic lesion
- A 25% increase in urine or serum monoclonal protein
- Patient can have received PS-341 (Velcade) previously and does not require a previous response.
Patients must have measurable disease. One or more of the following must be present to qualify for this study:
- Serum M-component greater than or equal to 1.0 gm/dl (10.0 g/L) by serum protein electrophoresis
- Urine M-protein excretion > 200 mg/24 (0.2 g/24h) hours, by urine protein electrophoresis
- Abnormal serum free light chain ratio with elevated Kappa or Lambda light chains in serum
- Baseline measurements must be done within 21 days of study entry.
- Karnofsky Performance Status Scale > 60.
- Greater than or equal to 18 years of age.
- Expected survival of greater than 8 weeks.
- Swallow intact study medication tablets.
- Can follow directions or has a caregiver who will be responsible for administering study medication.
Exclusion Criteria:
- Previously treated with R115777 (Zarnestra).
- Undergone an allogeneic bone marrow transplant.
- A platelet count of <100,000 x 10 to the 9 power/L within 14 days before enrollment.
- Absolute neutrophil count of <1.0 x 10 to the 9 power/L within 14 days before enrollment.
- Measured creatinine > 1.5 X the upper limits of normal within 14 days before enrollment.
- Greater than or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
- Hypersensitivity to bortezomib, boron, mannitol or imidazole compounds
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening.
- Received other investigational drugs within 14 days of enrollment or immunotherapy within 30 days of enrollment.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Ongoing radiation therapy or radiation therapy within 14 days prior to first treatment.
- Cytotoxic chemotherapy within 30 days prior to first treatment.
- Therapy with high-dose corticosteroids within 14 days prior to first treatment.
Presence of any of the following excludes a patient from entering the study until such condition is resolved (determined within 14 days prior to the first treatment):
- Elevated total bilirubin > 2mg/dl, or direct bilirubin > 2 times the ULN.
- Serum glutamic oxaloacetic transaminase (AST, formerly SGOT) or serum glutamic pyruvic transaminase (ALT, formerly SGPT) > 2 times the ULN
- Serum calcium > 12 mg/dL.
- Concurrent serious infection.
- Life-threatening illness (unrelated to tumor).
- History of any other ACTIVE and INVASIVE cancer other than the present condition (except non-melanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
Prohibited/allowable medications or precautions:
- Enzyme-inducing anti-epileptic medications (e.g. phenytoin, phenobarbital, carbamazepine) are not allowed.
- Non-enzyme anti-epileptic medications will be allowed.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Phase I
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Phase I and II: 1.3mg/m2 iv days 1,4,8,11
Other Names:
Phase I: 100mg po BID days 1014 for Cohort 1, 200mg po BID days 1014 for Cohort 2, 300mg po BID days 1014 for Cohort 3. Phase II: Maximum Tolerated Dose (MTD)
Other Names:
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Experimental: Phase II
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Phase I and II: 1.3mg/m2 iv days 1,4,8,11
Other Names:
Phase I: 100mg po BID days 1014 for Cohort 1, 200mg po BID days 1014 for Cohort 2, 300mg po BID days 1014 for Cohort 3. Phase II: Maximum Tolerated Dose (MTD)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose Limiting Toxicity (DLT)
Time Frame: Average of 6 months
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Determine the dose limiting toxicity at 3 weeks post treatment
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Average of 6 months
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Maximum Tolerated Dose
Time Frame: Average of 6 months
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Determine the maximum tolerated dose
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Average of 6 months
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Response Rates
Time Frame: Average of 6 months
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Determine response rates after 8 cycles of treatment
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Average of 6 months
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Toxicity
Time Frame: Average of 6 months
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Determine toxicity profiles
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Average of 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival
Time Frame: Average of 12 months
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Determine progression free survival
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Average of 12 months
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Collaborators and Investigators
Investigators
- Principal Investigator: Melissa Alsina, M.D., H. Lee Moffitt Cancer Center and Research Institute
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Antineoplastic Agents
- Bortezomib
- Tipifarnib
Other Study ID Numbers
- MCC-13971
- 7032 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma
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Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
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National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
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Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on PS-341
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Mayo ClinicNational Cancer Institute (NCI)CompletedLeukemia | Chronic Myeloproliferative DisordersUnited States
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M.D. Anderson Cancer CenterMillennium Pharmaceuticals, Inc.CompletedLeukemiaUnited States
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Jules Bordet InstituteCompletedCarcinoma Breast Stage IVBelgium
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M.D. Anderson Cancer CenterMillennium Pharmaceuticals, Inc.CompletedLymphoma, B-CellUnited States
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M.D. Anderson Cancer CenterMillennium Pharmaceuticals, Inc.CompletedOvarian Cancer | Fallopian Tube Cancer | Primary Peritoneal CancerUnited States
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Rasim GucalpMillennium Pharmaceuticals, Inc.TerminatedNon-small Cell Lung CancerUnited States
-
M.D. Anderson Cancer CenterCompletedMultiple MyelomaUnited States
-
Beijing Chao Yang HospitalEnrolling by invitationMultiple Myeloma | BortezomibChina
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Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedGraft-versus-Host DiseaseUnited States
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University of ChicagoNational Cancer Institute (NCI)Completed