Clinical trial NCT01096342: Dinaciclib in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official title: Phase II Trial of Cdk Inhibitor SCH 727965 in Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Multiple Myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-03-31
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Confirmed Responses, Defined to be an sCR, CR, VGPR, or PR Noted as the Objective Status on Two Consecutive Evaluations.
timeFrame: Up to 3 years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Time from registration to progression or death due to any cause, assessed up to 3 years
measure: Duration of Response
timeFrame: 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
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: Mayo Clinic
name: Shaji Kumar
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.