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Study Summary
No. 2007-0716:.......Myeloma......Sheeba K. Thomas......Lymphoma/Myeloma
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Study Summary Title
Study Summary
Number:
2007-0716
Study Title:A Phase II, Randomized, Double-blind, Placebo-controlled Study Comparing the Combination of CNTO 328 (Anti-IL-6 Monoclonal Antibody) and Velcade versus Velcade Alone in Subjects with Relapsed or Refractory Multiple Myeloma
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Physician New Patient Referral
Name:Sheeba K. ThomasPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Lymphoma/MyelomaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2860
Contact us about clinical trials
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General Information
Disease Group:MyelomaSupported By:Centocor, Inc
Phase of Study:Phase IIReturn
Visit:
Days 1,4,8,11,15,22,25,29,32,36 during the treatment phase.
Days 1,8,15,22,29 during the maintenance phase.
Treatment
Agents:
CNTO 328
Velcade
Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
No hospitalization required.
Description/
Intervention:
The goal of this clinical research study is to compare the safety of CNTO 328
given with Velcade™ (bortezomib) to the safety of bortezomib given alone for
the treatment for MM.
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Study Objectives / Outcomes
The primary objective of Part 1 of the study is to assess the safety of CNTO 328 when administered as an IV infusion in combination with bortezomib in subjects with relapsed or refractory multiple myeloma.

The primary objective of Part 2 of the study is to compare the efficacy, in terms of progression-free survival (PFS), of CNTO 328 when administered as an IV infusion in combination with bortezomib versus bortezomib alone in subjects with relapsed or refractory multiple myeloma.

The secondary objectives of the study are to assess other efficacy endpoints, safety, population pharmacokinetics, pharmacodynamics, and immune response of CNTO 328 in subjects with relapsed or refractory multiple myeloma.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:12/20/2007
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:290
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Male or female age >/=18 years

2) Signed informed consent obtained prior to any study-specific screening procedures

3) Confirmed diagnosis of multiple myeloma

4) Measurable secretory disease defined as either serum monoclonal paraprotein, (M-protein) >/= 1 g/dL or urine monoclonal (light chain) protein (> 200 mg/24 hours)

5) Documented disease progression (per EBMT criteria) during or after initial response to at least 1 prior line of txt but not > 3, or no response to previous txt (primary refractory disease), or undergone or are unsuitable for autologous hematopoietic stem cell transplantation, a) single line of txt may consist of 1 or more drugs such as, melphalan + prednisone; vincristine + conventional doxorubicin (or Doxil/Caelyx) + dexamethasone (VAD/DVd); lenalidomide; or high dose + corticosteroid w/ or w/o thalidomide (rituximab alone or experimental agents alone should not be considered line of txt).

6) Continued from Inclusion #5: (b) A single line of therapy may include induction chemotherapy followed by hematopoietic stem cell transplantation and maintenance therapy or progression of disease before a response during the initial line of therapy (primary refractory disease) with a regimen that may have contained an anthracycline, an alkylating agent, or high-dose corticosteroids (rituximab alone or experimental agents alone should not be considered a line of therapy)

7) Continued from Inclusion #6: Progressive disease (PD) defined by EBMT criteria: PD(for subjects not in CR) requires 1 or more of the following: > 25% increase in the level of the serum M-protein, which must also be an absolute increase of at least 5 g/L and confirmed by at least 1 repeated investigation ; > 25% increase in the 24 hour urinary light chain excretion, which must also be an absolute increase of at least 200 mg/24 hour and confirmed by at least 1 repeated investigation.

8) Continued Inclusion from # 7 : > 25% increase in plasma cells in either bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10%; Definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of new bone lesions or soft tissue plasmacytomas. Development of compression fracture does not exclude continued response and may not indicate progression; Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.8 mmol/L) not attributable to any other cause.

9) ECOG performance status score of </= 2

10) Subjects experiencing toxicities resulting from previous therapy must have fully recovered or stabilized to </= Grade 1

11) Subjects of childbearing potential must use adequate birth control measures. Female subjects of childbearing potential must have a negative serum pregnancy test at screening

12) Adequate bone marrow, liver, and renal function at first dose/randomization as described below: Hgb >/= 7.5 g/dL (4.7 mmol/L; 75 g/L) with or without transfusion dependency; Plts >/= 50,000/mm^3 without transfusion dependency; ANC >/= 1000 mm^3 without hematopoietic cytokine support; AST, ALT, and alkaline phosphatase </= 3 x ULN; Bilirubin </= 2 x ULN; Calculated creatinine clearance >/= 20 mL/min; Corrected serum calcium < 12 mg/dL (3.0 mmol/L) or ionized calcium < 6.5 mg/dL (1.6 mmol/L). This level may be achieved by treatment but it must be reached before the pt is randomized

13) Able to adhere to study visit schedule and all protocol requirements

Exclusion Criteria:1) Prior treatment with bortezomib

2) Hypersensitivity or allergic reactions to boron or mannitol, or compounds containing these components

3) >/= Grade 2 peripheral neuropathy (according to NCI CTCAE, Version 3.0)

4) Treatment with systemic cancer therapy (including clarithromycin) or radiotherapy within 30 days of randomization

5) Treatment with nitrosoureas within 42 days of first dose/randomization

6) Major surgery within 30 days of first dose/randomization or planning to have surgery (except for minor surgical procedures) during the study

7) Received any investigational drug/agent within 30 days or 5 half-lives (whichever is longer) of first dose/randomization

8) Received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant

9) Has clinically significant residual toxicities associated with prior autologous bone marrow or autologous peripheral blood stem cell transplant.

10) Administered platelet transfusion or neutrophil growth factor within 2 weeks prior to the collection of screening hematology laboratory sample

11) Transplanted solid organ with the exception of a corneal transplant (>/= 3 months prior to first dose/randomization)

12) Received any mAb within 60 days of first dose/randomization

13) Serious concurrent illness (medical or psychiatric), uncontrolled infection (including acute, diffuse infiltrative pulmonary disease), or any uncontrolled medical condition (eg, uncontrolled diabetes), including the presence of laboratory abnormalities, that places the subject at unacceptable risk by participating in the study or confounds the ability to interpret data from the study

14) Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class II or higher heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic, clinically significant conduction system abnormalities, baseline QTc interval > 450 milliseconds, history of hypokalemia, or any cardiac condition that is >/= Grade 3

15) Prior or concomitant malignancy (other than multiple myeloma) except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer for which the subject has been disease-free for >/= 3 years

16) Any other concomitant disease-related treatment such as, immunotherapy, biotherapy, radiotherapy, chemotherapy, investigative therapy, or immunosuppressive therapy/corticoid steroids

17) Vaccinated with live, attenuated vaccines within 4 weeks of the first administration of CNTO 328/placebo

18) Known to be seropositive for HIV, or active hepatitis A, B or C infection

19) Pregnant or lactating women

20) Known allergies or clinically significant reactions to murine, chimeric, or human proteins

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Links
Registration Number: NCT00401843
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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