Dinaciclib in Treating Patients With Relapsed or Refractory Multiple Myeloma

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Refractory Multiple Myeloma

Treatments

Other: laboratory biomarker analysis

Drug: dinaciclib

Study type

Interventional

Funder types

NIH

Identifiers

NCT01096342

P30CA015083 (U.S. NIH Grant/Contract)

MAYO-MC0888

8288 (Other Identifier)

NCI-2012-02795 (Registry Identifier)

N01CM62205 (U.S. NIH Grant/Contract)

MC0888 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

16 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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