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A Phase 2 Study of AZD6244 in Multiple Myeloma

Phase 2
18 Years
Open (Enrolling)
Refractory Multiple Myeloma

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Trial Information

A Phase 2 Study of AZD6244 in Multiple Myeloma


I. To assess the response rate of AZD6244 hydrogen sulfate capsules in patients with
relapsed or refractory MM.


I. To evaluate the toxicity of AZD6244 in patients with MM. II. To estimate progression-free
survival and duration of response to AZD6244. III. To test whether AZD6244 hydrogen sulfate
capsules downregulate tumor cell pERK1/2.


Patients receive selumetinib orally twice daily (BID) on days 1-28. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 weeks.

Inclusion Criteria:

- Confirmed diagnosis of multiple myeloma with relapsed or refractory disease following
at least two prior therapies

- Measurable disease defined as:

- Serum monoclonal protein >= 1 gm/dL or

- Urine monoclonal protein of >= 200 mg/24 hours, or

- Measurable free light chains by free light chain assay of >= 10 mg/dL with
abnormal kappa to lambda free light chain ratio, or

- Measurable bone disease, defined as >= 1 unidimensionally measurable lesion
(longest diameter to be recorded) >= 20 mm with conventional techniques or >= 10
mm with spiral CT scan (for patients with lytic bone disease)

- ECOG performance status =< 2

- Absolute neutrophil count: >= 1,000/μL (independent of blood cell growth factors)

- Platelets: >= 75,000/μL (independent of blood cell growth factors or transfusion)

- Total bilirubin: =< 1.5 x upper normal limit; however, patients with documented
Gilbert's syndrome are eligible

- AST(SGOT)/ALT(SGPT): < 2.5 x ULN

- Creatinine: < 3.0 x ULN

- Known HIV infected patients meeting the following characteristics are eligible:

- CD4 cell count >= 500/mm^3

- Meeting either of the following:

- Willing to suspend antiretroviral therapy for duration of protocol therapy

- On stable regimen of combination antiretroviral therapy that does not
include either zidovudine or stavudine for at least 12 weeks and without
evidence of toxicity

- No HIV-associated condition that defines AIDS

- Prior allogeneic stem cell transplant is allowed provided that all of the following
conditions are met:

- >= 6 months have elapsed since allogeneic transplant

- No Graft vs. Host Disease (GVHD) is present

- Not currently on immunosuppressive therapy

- Women of child-bearing potential must agree to use a medically accepted form of
contraception prior to, during, and for four weeks following study treatment; men
must agree to use a medically accepted form of contraception prior to, during, and
for sixteen weeks following study treatment

- Able and willing to provide a written informed consent

- Prior palliative and/or localized radiation therapy is permitted, provided at least
14 days have passed from date of last radiation therapy

- Pulse oximetry of >= 95% on room air

Exclusion Criteria:

- Any concurrent condition or planned treatment that would compromise study objectives
or represent an unacceptable patient risk, including but not limited to:

- Planned concurrent treatment for multiple myeloma other than bisphosphonates;
ongoing corticosteroids for indications other than multiple myeloma allowed as
long as the dose does not exceed 60mg of prednisone per day or equivalent

- Persisting effects of any previous or ongoing treatment that might compromise
delivery of study treatment or assessment of adverse events

- Planned concurrent treatment with any other investigational agents

- Cytotoxic chemotherapy less than 2 weeks, or biologic therapy less than 2 weeks, or
corticosteroids less than 2 weeks prior to registration

- No other malignancy unless the patient has been disease-free for >= 1 year

- Known multiple myeloma of central nervous system or leptomeninges

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to AZD6244

- Previous MEK inhibitor use

- Uncontrolled hypertension, i.e., persistent blood pressure (BP) of >= 160/95

- Significant cardiovascular disease (New York Heart Association Class II, III or IV
cardiac disease), hypertrophic cardiomegaly or restrictive cardiomyopathy, myocardial
infarction within the past 6 months, unstable angina, unstable arrhythmia unstable or
a need for anti-arrhythmic therapy (use of medication for atrial fibrillation is
allowed, if stable for at least 3 months)

- Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory
bowel disease), or significant bowel resection that would preclude adequate

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant or nursing

- LVEF =< 45% by ECHO or MUGA scan

- Any requirement for supplemental oxygen

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response (sCR+CR++VGPR+PR)

Outcome Time Frame:

Up to 2 years

Safety Issue:


Principal Investigator

Steven Grant

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

March 2010

Completion Date:

Related Keywords:

  • Refractory Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612
University of North CarolinaChapel Hill, North Carolina  27599
National Institutes of HealthBethesda, Maryland  20892
Virginia Commonwealth UniversityRichmond, Virginia  
Billings ClinicBillings, Montana  59107-7000
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201