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A Randomized Phase III Study of CC-5013 Plus Dexamethasone Versus CC-5013 Plus Low Dose Dexamethasone in Multiple Myeloma With Thalidomide Plus Dexamethasone Salvage Therapy for Non-Responders


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

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Trial Information

A Randomized Phase III Study of CC-5013 Plus Dexamethasone Versus CC-5013 Plus Low Dose Dexamethasone in Multiple Myeloma With Thalidomide Plus Dexamethasone Salvage Therapy for Non-Responders


PRIMARY OBJECTIVES:

I. To evaluate the response rate and toxicity of CC-5013 (lenalidomide) plus dexamethasone
(standard dose) versus CC-5013 plus low dose dexamethasone in patients with newly diagnosed
myeloma at any time in the first 4 cycles of treatment and to determine if CC-5013 plus low
dose dexamethasone will have similar response rate with lower toxicity (First Phase).

SECONDARY OBJECTIVES:

I. To evaluate the response rate of thalidomide plus dexamethasone (Thal/Dex) in patients
with newly diagnosed myeloma who do not achieve a complete or partial response (as defined
in Section 6.2.1 and 6.2.2) at any time in the first 4 cycles with the CC-5013 and
dexamethasone combination in either of the two arms (First Phase).

II. To study the effect of CC-5013 on bone marrow microvessel density and angiogenesis
grade, on PCLI, and on the expression of vascular endothelial growth factor (VEGF) and basic
fibroblast growth factor (bFGF) in the marrow (First Phase).

III. To study the effect of CC-5013 and dexamethasone on bone marrow mesenchymal progenitor
cells (MPCs) (First Phase).

IV. To evaluate in a separate expansion phase (Addendum #6) the efficacy of aspirin (325
mg/day) versus Coumadin (dose adjusted to maintain a target INR of 2-3) in preventing DVT in
patients with newly diagnosed myeloma receiving CC-5013 plus standard dose dexamethasone.
This separate expansion phase of the trial that will start after accrual to the first phase
of the trial testing the primary objective listed above is completed.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2
treatment arms.

Arm I: Patients receive oral lenalidomide once daily on days 1-21, oral acetylsalicylic acid
(or other deep vein thrombosis prophylaxis at the discretion of the principal investigator)
once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12,
and 17-20.

Arm II: Patients receive oral lenalidomide and acetylsalicylic acid as in arm I and low-dose
oral dexamethasone once daily on days 1, 8, 15, and 22.

In both arms, courses repeat every 28 days in the absence of unacceptable toxicity or
disease progression. Patients not responding at any point during the first 4 courses of
lenalidomide and dexamethasone are assigned to 1 of 2 salvage therapy arms. Patients who
progress during treatment on arms I or II have the option to register on salvage therapy
arms III or IV respectively.

Arm III (patients with no response after treatment on arm I): Patients receive oral
thalidomide once daily on days 1-28 and standard-dose oral dexamethasone once daily on days
1-4, 9-12, and 17-20.

Arm IV (patients with no response after treatment on arm II): Patients receive oral
thalidomide as in arm III and low-dose oral dexamethasone once daily on days 1, 8, 15, and
22.

In both salvage therapy arms, courses repeat every 28 days in the absence of unacceptable
toxicity or disease progression. After completion of 4 courses of therapy, patients may
undergo stem cell harvest (using growth factors only) for cryopreservation.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
annually for 2 years.


Inclusion Criteria:



- Patients must be diagnosed with symptomatic multiple myeloma within the past 90 days
confirmed by the following:

- Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells or
biopsy proven plasmacytoma which must be obtained within 4 weeks prior to
randomization

- Measurable levels of monoclonal protein (M protein): >= 1.0 g/dL on serum
protein electrophoresis or >= 200 mg of monoclonal light chain on a 24 hour
urine protein electrophoresis which must be obtained within 4 weeks prior to
randomization Please note that if both serum and urine m-components are present,
both must be followed in order to evaluate response

- Hemoglobin > 7 g/dL

- Platelet count > 75,000 cells/mm^3

- Absolute neutrophil count > 1000cells/mm^3

- Creatinine < 2.5 mg/dL and creatinine clearance (measured or calculated) >= 60 mL/min

- Bilirubin < 1.5 mg/dL

- SGPT (ALT) and SGOT (AST) =< 2.5 times the upper limit of normal

- No prior systemic therapy with the exception of bisphosphonates for multiple myeloma

- Prior glucocorticosteroid therapy for the treatment of multiple myeloma is not
permitted; prior systemic glucocorticosteroid use for the treatment of non-malignant
disorders is permitted; concurrent use after registration on the study should be
restricted to the equivalent of prednisone 10 mg per day; prior or concurrent topical
or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is
permitted

- Prior palliative and/or localized radiation therapy is permitted provided at least 4
weeks have passed from date of last radiation therapy to date of registration;
patients with prior solitary plasmacytoma treated with radiation therapy with
curative intent are eligible if the disease has now progressed to active multiple
myeloma meeting all the eligibility criteria for this protocol

- Patients must not have active, uncontrolled seizure disorder. Patients must have had
no seizures in the last 6 months

- Patients must not have uncontrolled intercurrent illness including uncontrolled
hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled
cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would
limit compliance with the study, or a prior history of Stevens Johnson Syndrome

- ECOG performance status 0, 1, or 2

- Patients with smoldering myeloma or monoclonal gammopathy of undetermined
significance are not eligible

- Patients must not have grade 2 or higher peripheral neuropathy due to other medical
conditions at the time of randomization

- Patients must not have active, uncontrolled infection

- Patients must not have a history of current or previous deep vein thrombosis or
pulmonary embolism regardless of whether or not the patient is receiving
anticoagulation therapy

- For patients registered prior to activation of Addendum # 6; patients must be
willing and able to take prophylaxis with either aspirin at 325 mg/day or
alternative prophylaxis with either low molecular weight heparin or Coumadin

- For patients registered after activation of Addendum # 6; patients entering the
expansion phase of the protocol, which tests anticoagulant prophylaxis, must be
able and willing to be randomized between aspirin at 325 mg/day and Coumadin

- Female patients MUST NOT be pregnant or breastfeeding; due to the potential
teratogenic properties of CC 5013, and the known teratogenicity associated with
thalidomide, the use of these drugs in this patient population is ABSOLUTELY
CONTRAINDICATED

- Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days and again
within 24 hours prior to starting course 1 of lenalidomide; further, they must either
commit to continued abstinence from heterosexual intercourse or begin TWO acceptable
methods of birth control: one highly effective method (IUD, birth control pills,
tubal ligation or partner's vasectomy) and one additional effective method (condom,
diaphragm or cervical cap); FCBP must also agree to ongoing pregnancy testing; men
must agree to use a latex condom during sexual contact with a FCBP, even if they have
had a successful vasectomy starting 4 weeks prior to and while taking CC5013 or
thalidomide and for four weeks after discontinuing this therapy. A FCBP is a sexually
mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or
2) has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months); all patients must
be counseled by a trained counselor every 28 days about pregnancy precautions and
risks of fetal exposure

- Patients with a history of prior malignancy are eligible provided there is no active
malignancy and a low expectation of recurrence within 6 months

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Response rate based on IBMTR/ABMTR

Outcome Time Frame:

Up to 7 years

Safety Issue:

No

Principal Investigator

S. Vincent Rajkumar

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03150

NCT ID:

NCT00098475

Start Date:

October 2004

Completion Date:

Related Keywords:

  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

Eastern Cooperative Oncology GroupBoston, Massachusetts  02215