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Recurrent Plasma Cell MyelomaPhase 1NCT01711528

Dinaciclib, Bortezomib, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

A Phase 1 study testing Bortezomib, Dexamethasone and Dinaciclib in people with Recurrent Plasma Cell Myeloma, run by National Cancer Institute (NCI) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of dinaciclib and bortezomib when given together with dexamethasone in treating patients with multiple myeloma that has returned after a period of improvement. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Plasma Cell Myeloma
What is being tested?
Bortezomib, Dexamethasone and Dinaciclib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
6 sitesUnited States
Study dates
19 Dec 2012to 22 Nov 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Serum creatinine =< 2.5 mg/dL
  • 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
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  • 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

Who cannot join

  • Any of the following recent therapies:
  • 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
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  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Aspirus UW Cancer Center

    Wisconsin Rapids, Wisconsin, 54494

Other trials in United States

About this study

Official title: Phase 1 Clinical Trial of a Novel CDK Inhibitor Dinaciclib (SCH 727965) in Combination With Bortezomib and Dexamethasone in Relapsed Multiple Myeloma

This phase I trial studies the side effects and best dose of dinaciclib and bortezomib when given together with dexamethasone in treating patients with multiple myeloma that has returned after a period of improvement. Dinaciclib and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving dinaciclib and bortezomib together with dexamethasone may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Bortezomib, Dexamethasone, Dinaciclib, Laboratory Biomarker Analysis
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BortezomibDrug

    Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341

    Given SC

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO

  • DinaciclibDrug

    Also called CDK Inhibitor SCH 727965, MK-7965, SCH 727965

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01711528
Study groupRoleWhat they receive
Schedule I (dinaciclib, bortezomib, dexamethasone)ExperimentalPatients 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.
Receives: Drug: Bortezomib; Drug: Dexamethasone; Drug: Dinaciclib; Other: Laboratory Biomarker Analysis
Schedule II (dinaciclib, bortezomib, dexamethasone)ExperimentalPatients 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.
Receives: Drug: Bortezomib; Drug: Dexamethasone; Drug: Dinaciclib; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    MTD is defined as the dose level below the lowest dose that induces DLT in at least one-third of patients.

    Measured: Up to 28 days

Secondary outcomes (5)

  1. Incidence of adverse events, graded according to NCT CTCAE version 4.0

    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.

    Measured: Up to 3 months

  2. Overall response rate

    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).

    Measured: Up to 3 months

  3. Time to progression

    Summarized descriptively.

    Measured: Up to 3 months

  4. Time to treatment failure

    Summarized descriptively.

    Measured: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patients, assessed up to 3 months

  5. Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin)

    Summarized descriptively.

    Measured: Up to 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2012 (estimated)
  2. Study start19 Dec 2012
  3. Primary completion22 Nov 2016
  4. Study completion22 Nov 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01711528
Sponsor's protocol ID
NCI-2012-01737
Other IDs
NCI-2012-01737, MC1113, NCI 9157, CDR0000741989, MC1113, 9157, P30CA015083, R01CA167511
Status last verified
May 2018
First submitted
18 Oct 2012
Last updated
11 May 2018
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bortezomib, Dexamethasone and Dinaciclib in people with Recurrent Plasma Cell Myeloma, run by National Cancer Institute (NCI) at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01711528.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2018.

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