Phase 1 Clinical Trial of a Novel CDK Inhibitor Dinaciclib (SCH 727965) in Combination With Bortezomib and Dexamethasone in Relapsed Multiple Myeloma
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 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
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) 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 and 90 days.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of dinaciclib and bortezomib when given together with dexamethasone, based on incidence of dose-limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
MTD is defined as the dose level below the lowest dose that induces DLT in at least one-third of patients.
Course 1 (up to 28 days)
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|Mayo Clinic in Arizona||Scottsdale, Arizona 85259-5404|
|Mayo Clinic in Florida||Jacksonville, Florida 32224|
|M D Anderson Cancer Center||Houston, Texas 77030|
|University of Wisconsin Cancer Center Riverview||Wisconsin Rapids, Wisconsin 54494|