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Study Summary
No. 2004-0492:.......Lymphoma; Myeloma; Phase I Studies......Razelle Kurzrock......Investigational Cancer Therapeutics
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Study Summary Title
Study Summary
Number:
2004-0492
Study Title:A Phase I Study of Multiple Intravenous Administrations of a Chimeric Antibody Against Interleukin-6 (CNTO 328) in Subjects with B-cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's Disease
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Physician New Patient Referral
Name:Razelle KurzrockPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Investigational Cancer TherapeuticsReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-1226
Contact us about clinical trials
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General Information
Disease Group:Lymphoma
Myeloma
Phase I Studies
Supported By:N/A
Phase of Study:Phase IReturn
Visit:
Patients will return to MDACC every 1 to 2 weeks
Treatment
Agents:
CNTO 328Home Care:N/A
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to compare different combinations
of dose levels and schedules of anti-IL-6 antibody (CNTO 328, siltuximab), to
see which dose/schedule of CNTO 328 can best be given safely and to see if CNTO
328 has an effect on the disease.
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Study Objectives / Outcomes
The primary objective is to assess the safety and pharmacokinetics of multiple dosing regimens of CNTO 328 administered as an intravenous (IV) infusion in subjects with B-cell non-Hodgkin's lymphoma (including chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL] and Waldenstrom's macroblogulinemia [WM]), multiple myeloma, or Castleman's Disease.

The secondary objectives are to assess the pharmacodynamics, immune response, and clinical effects of CNTO 328 administered biweekly as an IV infusion in subjects with B cell non-Hodgkin's lymphoma (including CLL/SLL and WM), multiple myeloma, or Castleman's Disease.
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Study Status Information
Study Activation / Registration Date:06/08/2005
IRB Review and Approval Date:09/01/2004
Study Type:Therapeutic
Recruitment Status:Closed
Projected Accrual:78
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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) Age greater than or equal to 18 years old

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

3) Histological documentation of either B cell non-Hodgkin's lymphoma, multiple myeloma, or Castleman's Disease

4) Disease which has progressed on or after standard therapy or for which there is no effective standard therapy, or which is not suitable for standard therapy at the discretion of the treating physician. (B cell non-Hodgkin's lymphoma: >/=1 measurable lesion; for CLL/SLL: >/= 1 measurable lesion or > 5000/microliter mature appearing peripheral blood lymphocytes; no subjects with > 55% prolymphocytes and/or 15,000/microliter prolymphocytes; subjects with active autoimmune hemolytic anemia as defined by Coomb's positive hemolytic process will also be excluded; for WM: measurable serum M-protein;

5) for multiple myeloma: measurable monoclonal paraprotein [M-protein, serum and/or 24-hr urine or 30% plasma cells in the bone marrow]; for Castleman's Disease: either localized disease which is not amenable to surgical resection, or multicentric disease; and symptomatic disease which requires therapy.)

6) Detectable serum CPR according to the standard assay of the central laboratory (this criterion is not applicable for Castleman's Disease).

7) Life expectancy of greater than or equal to 4 months at screening

8) Karnofsky performance status of greater than or equal to 60

9) At least 4 weeks since prior systemic therapy, radiotherapy or surgery; subjects must have recovered or stabilized from toxicities resultant from previous therapy

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

11) Adequate bone marrow function: (i) Hgb greater than or equal to 8.0 g/dL; without transfusion dependency. For Cohort 7, Hgb greater than or equal to 7.5 g/dL. (ii) ANC of greater than or equal to 1,000/microliter; (iii) Platelets greater than or equal to 75,000/microliter; without transfusion dependency

12) Adequate renal and liver function; (i) Serum creatinine less than or equal to 2.0 mg/dL for non-Hodgkin's lymphoma (including CLL/SLL and WM); less than or equal to 3.0 mg/dL for multiple myeloma and Castleman's Disease. AST, ALT, Alkaline phosphatase, total bilirubin less than or equal to 3 x ULN if no liver mets; less than or equal to 5 x ULN for liver mets; or Alk phos less than or equal to 5 x ULN for bone involvement

Exclusion Criteria:1) Received any investigational drug within 30 days or 5 half-lives of the investigational drug, whichever is longer.

2) History of receiving murine or human/murine recombination rpoducts, such as G250, BE-8 and other monoclonal antibodies. This exclusion will be evaluated by the Centocor medical monitor for Castleman's Disease subjects. (Note: prior rituximab treatment is not an exlcusion criterion.) For Cohort 7, subjects refractory to specific IL-6 or IL-6 receptor antagonists.

3) Serious concurrent illness or significant cardiac disease characterized by signficiant ischemic coronary disease or congestive heart failure

4) Clinically significant infection that is chronic, recurrent, or active.

5) Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening) or having received an allogeneic bone marrow transplant or an allogeneic peripheral blood stem cell transplant

6) Central nervous system (CNS) metastatic disease

7) Concomitant or prior malignancy (other than the one under study) 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 greater than or equal to 3 years

8) Any other concomitant immunotherapy, biotherapy, treatment with G-CSF (or GM-CSF), radiotherapy, chemotherapy, investigative therapy, or immunosuppressive therapy. Exception: Castleman's Disease; daily maintenance dose of prednisone of up to 1 mg/kg or the equivalent will be allowed and providing no change has been made to the dosage within 4 weeks of first dose of study drug.

9) Planned surgery (except for minor surgical procedures) during study period

10) Pregnant or lactating women

11) Known HIV seropositivity; known HIV, hepatitis B or hepatitis C infection. For Cohort 7, known human herpesvirus-8 (HHV-8) seropositivity.

12) Autoimmune disease (e.g., inflammatory bowel disease such as Crohn's disease, systemic lupus,multiple sclerosis)

13) Any uncontrolled medical condition, including the presence of laboratory abnormalities that places the subject at unacceptable risk by participating in the study or confounds ability to interpret data from the study.

14) Vaccinated with live, attenuated vaccines within 4 weeks of the first administratino of CNTO 328. Inactivated injectable influenza vaccine is permitted.

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Links
Registration Number: NCT00412321
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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