Dinaciclib, Bortezomib, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT01711528|
Recruitment Status : Completed
First Posted : October 22, 2012
Last Update Posted : May 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Plasma Cell Myeloma||Drug: Bortezomib Drug: Dexamethasone Drug: Dinaciclib Other: Laboratory Biomarker Analysis||Phase 1|
I. To determine the maximally tolerated doses of dinaciclib and bortezomib, when used in combination, in two different schedules, for treatment of relapsed multiple myeloma.
I. To determine the toxicities associated with dinaciclib and bortezomib, when used in combination, for treatment of relapsed multiple myeloma.
II. To determine the overall response rate associated with dinaciclib and bortezomib, when used in combination, for treatment of relapsed multiple myeloma.
III. To explore the differences in toxicity associated with two different schedules of dinaciclib and bortezomib used in combination.
I. To examine if expression levels of target cyclin dependent kinase (CDK): CDK 2,5,7 and 9 levels in cluster of differentiation (CD)138-purified tumor cells, will be correlated with response (clinical and molecular) to determine if high or low level target CDK expression, if present, influences dinaciclib efficacy.
II. To examine if immunoglobulin (Ig)H translocation status, P53 status and presence of v-myc myelocytomatosis viral oncogene homolog (avian) (Myc) amplification or rearrangement, determined on patient bone marrow before treatment, using a pre validated fluorescence in situ hybridization (FISH) panel to identify common myeloma translocations, will be correlated with molecular and/or clinical markers of drug activity, and to assess if specific genetic subgroups of myeloma tumors are responsive or resistant.
III. To determine the gene expression profiles of myeloma cells before and after treatment to understand the role of tumor gene dysregulation and/or dinaciclib induced effects on transcription.
OUTLINE: This is a dose-escalation study of dinaciclib and bortezomib. Patients are assigned to 1 of 2 treatment schedules.
SCHEDULE I: Patients receive dinaciclib intravenously (IV) over 2 hours and bortezomib subcutaneously (SC) or IV (if patients do not tolerate SC injection) on days 1, 8, and 15 and dexamethasone orally (PO) once daily (QD) on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
SCHEDULE II: Patients receive dinaciclib IV over 2 hours on day 1; bortezomib SC on days 1 and 8; and dexamethasone PO QD on days 1, 2, 8, and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and 3 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Clinical Trial of a Novel CDK Inhibitor Dinaciclib (SCH 727965) in Combination With Bortezomib and Dexamethasone in Relapsed Multiple Myeloma|
|Actual Study Start Date :||December 19, 2012|
|Actual Primary Completion Date :||November 22, 2016|
|Actual Study Completion Date :||November 22, 2016|
Experimental: Schedule I (dinaciclib, bortezomib, dexamethasone)
Patients receive dinaciclib IV over 2 hours and bortezomib SC or IV (if patients do not tolerate SC injection) on days 1, 8, and 15 and dexamethasone PO QD on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Experimental: Schedule II (dinaciclib, bortezomib, dexamethasone)
Patients receive dinaciclib IV over 2 hours on day 1; bortezomib SC on days 1 and 8; and dexamethasone PO QD on days 1, 2, 8, and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- MTD of dinaciclib and bortezomib when given together with dexamethasone, based on the incidence of dose-limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 28 days ]MTD is defined as the dose level below the lowest dose that induces DLT in at least one-third of patients.
- Incidence of adverse events, graded according to NCT CTCAE version 4.0 [ Time Frame: Up to 3 months ]The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. Toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
- Overall response rate [ Time Frame: Up to 3 months ]Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).
- Time to progression [ Time Frame: Up to 3 months ]Summarized descriptively.
- Time to treatment failure [ Time Frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patients, assessed up to 3 months ]Summarized descriptively.
- Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin) [ Time Frame: Up to 3 months ]Summarized descriptively.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01711528
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Virginia|
|Virginia Commonwealth University/Massey Cancer Center|
|Richmond, Virginia, United States, 23298|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Aspirus UW Cancer Center|
|Wisconsin Rapids, Wisconsin, United States, 54494|
|Principal Investigator:||Shaji Kumar||Mayo Clinic|