Dinaciclib, Bortezomib, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma
NCT ID: NCT01711528
Last Updated: 2018-05-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
41 participants
INTERVENTIONAL
2012-12-19
2016-11-22
Brief Summary
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Detailed Description
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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.
SECONDARY OBJECTIVES:
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.
TERTIARY OBJECTIVES:
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.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
Bortezomib
Given SC
Dexamethasone
Given PO
Dinaciclib
Given IV
Laboratory Biomarker Analysis
Correlative studies
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.
Bortezomib
Given SC
Dexamethasone
Given PO
Dinaciclib
Given IV
Laboratory Biomarker Analysis
Correlative studies
Interventions
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Bortezomib
Given SC
Dexamethasone
Given PO
Dinaciclib
Given IV
Laboratory Biomarker Analysis
Correlative studies
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Absolute neutrophil count \>= 1000/uL
* Untransfused platelet count \>= 75000/uL
* Hemoglobin \>= 8 g/dL
* Total bilirubin =\< 1.5 times institutional upper limit of normal (ULN)
* Patients with relapsed multiple myeloma who have already received one or more standard treatment regimens
* Measurable disease of multiple myeloma as defined by at least ONE of the following:
* Serum monoclonal protein \>= 1 g/dL
* \>= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
* Serum immunoglobulin free light chain \>= 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio
* Monoclonal bone marrow plasmacytosis \>= 30% (evaluable disease)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
* Adequate residual organ function per treating physician discretion; Note: there is no limit with regard to the number of prior therapies
* Provide informed written consent
* Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
* Willing to provide samples for correlative research purposes
* Willing to return to consenting institution for follow-up during the study
* Recovered (i.e., =\< grade 1 toxicity) from the reversible effects of prior antineoplastic therapy
Exclusion Criteria
* Alkylators (e.g. melphalan, cyclophosphamide) =\< 14 days prior to registration
* Anthracyclines =\< 14 days prior to registration
* High dose corticosteroids, immune modulatory drugs (thalidomide or lenalidomide), or proteosome inhibitors (bortezomib) =\< 7 days prior to registration
* Concomitant high dose corticosteroids (concurrent use of corticosteroids); EXCEPTION: patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than amyloid, i.e., adrenal insufficiency, rheumatoid arthritis, etc.
* Other active malignancy =\< 2 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
* Any of the following:
* Pregnant women or women of reproductive ability who are unwilling to use 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of study drug
* Nursing women
* Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 30 days after stopping treatment
* Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
* Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
* Peripheral neuropathy \>= grade 2 on clinical examination during the screening period
* Major surgery =\< 14 days prior to registration
* Currently taking strong or moderate inhibitors/inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); Note: dinaciclib is a CYP3A4 substrate; patients should not take grapefruit/grapefruit juice or St. John's wort; use of strong or moderate CYP3A4 inhibitors is prohibited from \< 7 days prior to registration; use of CYP3A4 inducers is prohibited from =\< 7 days prior to registration
* Any of the following conditions:
* Myocardial infarction =\< 6 months prior to registration or has New York Heart Association (NYHA) class III or IV heart failure
* Uncontrolled angina
* Severe uncontrolled ventricular arrhythmias
* Electrocardiographic evidence of acute ischemia
* Active conduction system abnormalities; NOTE: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
* Known hypersensitivity to bortezomib, boron, or mannitol
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study per the judgment of the treating physician
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Shaji Kumar
Role: PRINCIPAL_INVESTIGATOR
Mayo Clinic
Locations
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Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Mayo Clinic
Rochester, Minnesota, United States
M D Anderson Cancer Center
Houston, Texas, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Aspirus UW Cancer Center
Wisconsin Rapids, Wisconsin, United States
Countries
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Other Identifiers
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NCI-2012-01737
Identifier Type: REGISTRY
Identifier Source: secondary_id
MC1113
Identifier Type: -
Identifier Source: secondary_id
NCI 9157
Identifier Type: -
Identifier Source: secondary_id
CDR0000741989
Identifier Type: -
Identifier Source: secondary_id
MC1113
Identifier Type: OTHER
Identifier Source: secondary_id
9157
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2012-01737
Identifier Type: -
Identifier Source: org_study_id
NCT02668731
Identifier Type: -
Identifier Source: nct_alias
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