Dinaciclib in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT01096342 | Completed Phase 2 Results

• 6 other identifiers: NCI-2012-02795MAYO-MC0888MC08888288P30CA015083N01CM62205
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 6

Brief Summary

This phase II trial is studying how well giving dinaciclib works in treating patients with relapsed or refractory multiple myeloma. Dinaciclib may stop the growth of cancer cells by clocking some of the enzymes needed for cell growth.

Conditions

Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Confirmed Responses, Defined to be an sCR, CR, VGPR, or PR Noted as the Objective Status on Two Consecutive Evaluations.

  Complete Response (CR): Negative immunofixation of serum and urine Normalization of FLC ratio \< 5% plasma cells in bone marrow Disappearance of any soft tissue plasmacytomas Stringent Complete Response (sCR): CR, as above, with absence of clonal cells in bone marrow Partial Response (PR): One of the following: 1. A ≥ 50% reduction of measurable serum M-protein. 2. A reduction in 24h measurable urinary M-protein by ≥ 90% or to \<200 mg per 24h. 3. A ≥ 50% decrease in the difference between involved and uninvolved FLC levels. 4. ≥50% reduction in bone marrow plasma cells is required in place of Mprotein, provided baseline percentage was ≥ 30% 5. A ≥50% reduction in the size of soft tissue plasmacytomas. Very Good Partial Response (VGPR): PR as defined above in addition to having serum and urine M-component detectable by immunofixation but not on electrophoresis.

  Up to 3 years

Secondary Outcomes (2)

• Progression-free Survival

  Time from registration to progression or death due to any cause, assessed up to 3 years

• Duration of Response

  Date at which the patient's objective status is first noted to be either an sCR, CR, PR, or VGPR to the earliest date progression is documented, assessed up to 3 years

Study Arms (1)

Treatment

EXPERIMENTAL

Patients receive dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: dinaciclib; Other: laboratory biomarker analysis

Interventions

dinaciclib DRUG

Given IV

Also known as: CDK inhibitor SCH 727965, cyclin-dependent kinase inhibitor SCH 727965, SCH 727965

Treatment

laboratory biomarker analysis OTHER

Correlative studies

Treatment

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory multiple myeloma
• Measurable disease as defined by at least ONE of the following:
• Serum monoclonal protein \>= 1.0 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
• ≤ 5 prior therapies; stem cell transplantation and preceding induction therapy will be considered as one therapy; NOTE: Patients must not be candidates for stem cell transplantation or should have had stem cells collected previously
• Life expectancy of ≥ 3 months
• ECOG performance status of 0, 1 or 2
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 75,000/mcL
• Hemoglobin \>= 8 g/dL
• Total serum bilirubin within normal institutional limits
• AST (SGOT)/ALT(SGPT) =\< 2.5 X institutional ULN
• Creatinine \< 2.5 mg/dL
• Negative serum pregnancy test done ≤7 days prior to registration (for women of childbearing potential only); NOTE: Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

You may not qualify if:

• Any of the following prior therapies:
• Myelosuppressive therapy for myeloma ≤ 3 weeks prior to registration or those who have not recovered from acute reversible adverse events due to agents administered \> 3 weeks earlier
• Non-myelosuppressive agents like thalidomide or high dose corticosteroids ≤ 2 weeks prior to registration
• Receiving any other investigational agents
• Concomitant high dose corticosteroids
• NOTE: Concurrent use of corticosteroids, but 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.
• NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Active malignancy with the exception of non melanoma skin cancer or in situ cervical or breast cancer
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or nursing women; NOTE: Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SCH 727965, breastfeeding should be discontinued if the mother is treated with SCH 727965
• Currently taking inhibitors/inducers of CYP3A4; (SCH 727965 metabolizes via the CYP3A4 enzyme; there are potential drug interactions with concomitant use of CYP3A4 potent inhibitors/inducers; Principal Investigator should review each case and determine if patients on the CYP3A4 potent inhibitors/inducers are eligible and will make all effort to switch to alternative drugs; patients should not take grapefruit/ grapefruit juice or St. Johns' Wort)
• Men or women of childbearing potential who are unwilling to employ adequate contraception

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

National University Hospital

Singapore, 119074, Singapore

Location

Related Publications (1)

• Kumar SK, LaPlant B, Chng WJ, Zonder J, Callander N, Fonseca R, Fruth B, Roy V, Erlichman C, Stewart AK; Mayo Phase 2 Consortium. Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood. 2015 Jan 15;125(3):443-8. doi: 10.1182/blood-2014-05-573741. Epub 2014 Nov 13.

  PMID: 25395429 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

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

Results Point of Contact

• Title: Shaji Kumar, M.D.
• Organization: Mayo Clinic Cancer Center

kumar.shaji@mayo.edu

Study Officials

• Shaji Kumar

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2010
• First Posted: March 31, 2010
• Study Start: July 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2012
• Last Updated: June 18, 2014
• Results First Posted: February 25, 2013

Record last verified: 2013-12

Locations

US (5); SG (1)