Dinaciclib in Treating Patients With Relapsed or Refractory Multiple Myeloma

Phase II Trial of Cdk Inhibitor SCH 727965 in Multiple Myeloma

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.

Study Overview

• Status: Completed
• Conditions: Refractory Multiple Myeloma
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: dinaciclib

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the efficacy (overall response rate) of single agent SCH 727965 in patients with relapsed or refractory multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the toxicities associated with use of single agent SCH 727965 in patients with relapsed or refractory multiple myeloma.

II. To evaluate the response duration and progression free survival among patients with relapsed or refractory multiple myeloma undergoing treatment with single agent SCH 727965.

III. To study the effect of SCH 727965 on myeloma cell proliferation, apoptotic rates and to assess the ability of the drug to inhibit drug targets (cyclin dependent kinases, cdk in the myeloma cell.

OUTLINE: This is a multicenter, dose-escalation study.

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

Blood and bone marrow samples are collected periodically for correlative studies. (US sites only)

After completion of study treatment, patients are followed up for up to 3 years.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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
• Ability to understand and the willingness to sign a written informed consent document
• Willingness to provide blood and bone marrow samples for mandatory research component of this study; (US sites only)

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Patients receive dinaciclib IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: dinaciclib; Given IV; Other Names: SCH 727965; CDK inhibitor SCH 727965; cyclin-dependent kinase inhibitor SCH 727965

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: A ≥ 50% reduction of measurable serum M-protein.; A reduction in 24h measurable urinary M-protein by ≥ 90% or to <200 mg per 24h.; A ≥ 50% decrease in the difference between involved and uninvolved FLC levels.; ≥50% reduction in bone marrow plasma cells is required in place of Mprotein, provided baseline percentage was ≥ 30%; 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.	Time from registration to progression or death due to any cause, assessed up to 3 years
Duration of Response	The distribution of duration of response will be estimated using the method of Kaplan-Meier.	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: March 30, 2010
• First Submitted That Met QC Criteria: March 30, 2010
• First Posted (Estimate): March 31, 2010

Study Record Updates

• Last Update Posted (Estimate): June 18, 2014
• Last Update Submitted That Met QC Criteria: June 2, 2014
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Cyclin-Dependent Kinase Inhibitor Proteins
• Other Study ID Numbers: NCI-2012-02795 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA015083 (U.S. NIH Grant/Contract); N01CM62205 (U.S. NIH Grant/Contract); MAYO-MC0888; MC0888 (Other Identifier: Mayo Clinic); 8288 (Other Identifier: CTEP)