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

NCT01711528 | Completed Phase 1

• 10 other identifiers: NCI-2012-01737MC1113NCI 9157CDR00007419899157P30CA015083R01CA167511U01CA069912UM1CA186686UM1CA186716
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 6

Brief 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. 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.

Conditions

Recurrent Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (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.

  Up to 28 days

Secondary Outcomes (5)

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

  Up to 3 months

• Overall response rate

  Up to 3 months

• Time to progression

  Up to 3 months

• Time to treatment failure

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

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

  Up to 3 months

Study Arms (2)

Schedule I (dinaciclib, bortezomib, dexamethasone)

EXPERIMENTAL

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.

Drug: Bortezomib; Drug: Dexamethasone; Drug: Dinaciclib; Other: Laboratory Biomarker Analysis

Schedule II (dinaciclib, bortezomib, dexamethasone)

EXPERIMENTAL

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.

Drug: Bortezomib; Drug: Dexamethasone; Drug: Dinaciclib; Other: Laboratory Biomarker Analysis

Interventions

Bortezomib DRUG

Given SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Schedule I (dinaciclib, bortezomib, dexamethasone); Schedule II (dinaciclib, bortezomib, dexamethasone)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Schedule I (dinaciclib, bortezomib, dexamethasone); Schedule II (dinaciclib, bortezomib, dexamethasone)

Dinaciclib DRUG

Given IV

Also known as: CDK Inhibitor SCH 727965, MK-7965, SCH 727965

Schedule I (dinaciclib, bortezomib, dexamethasone); Schedule II (dinaciclib, bortezomib, dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Schedule I (dinaciclib, bortezomib, dexamethasone); Schedule II (dinaciclib, bortezomib, dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Aspirus UW Cancer Center

Wisconsin Rapids, Wisconsin, 54494, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; dinaciclib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Shaji Kumar

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2012
• First Posted: October 22, 2012
• Study Start: December 19, 2012
• Primary Completion: November 22, 2016
• Study Completion: November 22, 2016
• Last Updated: May 11, 2018

Record last verified: 2018-05

Locations

US (6)