Clinical trial NCT00412321: A Safety and Efficacy Study of CNTO 328 in Patients With B-Cell Non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's Disease
Official title: A Phase 1 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin
Multiple Myeloma
Giant Lymph Node Hyperplasia
Keywords: Lymphoma, Non-Hodgkin
Multiple Myeloma
Castleman's disease
intravenous
IL-6
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
First posted: 2006-12-18
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate of the study of different CNTO 328 doses and schedules and to see if CNTO 328 has any effect on Non-hodgkin's Lymphoma, Multiple Myeloma or Castleman's disease.

Detailed description: This research study will use a type of drug called anti-IL-6 antibody, also known as CNTO 328. An antibody is a substance in the body that fights infection. CNTO 328 is an investigational drug that has been shown to slow down tumor growth or shrink tumors when tested in animals. In a previous clinical trial in patients with multiple myeloma (blood cancer), CNTO 328 appeared to be a potent inhibitor of IL-6 . One study has been completed for kidney cancer. There are studies ongoing in humans with multiple myeloma and prostate cancer to see if CNTO 328 is safe and to see what effects it has on these types of cancer. This is an open-label, nonrandomized, dose-finding phase 1 study with CNTO 328 in patients with B- cell non-Hodgkin's Lymphoma, Multiple Myeloma, or Castleman's disease. The purpose of this study is to evaluate different doses and schedules of CNTO 328 to see which dose/schedule is safe. CNTO 328 will be given through a small tube that goes directly into your vein, called an intravenous (IV) infusion. Depending on when the patient enters the study, the patient will be assigned to receive one course of CNTO 328 in one of the following groups: Group 1: 3 mg/kg 2 hr IV infusion every 2 weeks for 4 doses. Group 2: 6 mg/kg 2 hr IV infusion every 2 weeks for 4 doses. Group 3: 12 mg/kg 2 hr IV infusion every 3 weeks for 3 doses. Group 4: 6 mg/kg 2 hr IV infusion every week for 7 doses. Group 5: 12 mg/kg 2 hr IV infusion every 2 weeks for 4 doses. Group 6: 12 mg/kg 1 hr IV infusion every 3 weeks for 3 doses. Group 7a: 9 mg/kg 1 hr IV infusion every 3 weeks. Group 7b: 12 mg/kg 1hr IV infusion every 3 weeks for Castleman's patients only. In Groups 1-5, the overall amount of study drug that will be given increases with each higher group. Group 1 will be filled before Group 2 starts and Group 2 will be filled before Group 3 starts, etc. In this way, CNTO 328 can be tested more safely. Both the patient and the study doctor will know to which group the patient is assigned. Patients will remain in the group that they are assigned to for the entire time of participation in the study. Up to 70 patients may take part in this study. Patients in Groups 1-6 will be in the study for up to 34 weeks prior to Post Study Follow-Up. Screening: up to 4 weeks before the first dose schedule of CNTO 328. Treatment: up to 6 weeks of treatment with CNTO 328. Extended Dosing: Patients assigned to Groups 1-6, and their cancer or disease has become stable or better while receiving CNTO 328, may be able to receive additional courses of study drug. Patients in Group 7 will be in the study until their disease gets worse, they can no longer tolerate CNTO 328, the study doctor feels it is in their best interest to stop CNTO 328 or they longer wish to participate in the study. Long Term Follow-Up: Patients will be contacted by telephone every six months after the last infusion of study drug to assess the patient's disease status and survival. Dose (6-12 mg/kg) and frequency (weekly or 2 or 3 week intervals) of dosing depends upon Group assignment. CNTO 328 will be given through a small tube that goes directly into your vein, called an intravenous (IV) infusion. The infusion will take about 2 hours to complete for groups 1-5 and 1 hour for Groups 6 and 7. In Groups 1-6, CNTO 328 will be given once every 1, 2 or 3 weeks from days 1 to 43 depending on treatment assignment. In Group 7a and Group 7b, CNTO 328 will be given on day 1 of each 21 day cycle.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with B-cell non-Hodgkin's lymphoma, multiple myeloma, or Castleman's 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
* Detectable serum C-Reactive Protein
* At least 4 weeks since prior systemic therapy, radiotherapy, or surgery
* Must meet protocol lab criteria (adequate bone marrow, liver and renal function) to be assessed at patient's first visit to the study center

Exclusion Criteria:

* Received any investigational drug within 30 days or 5 half-lives of the investigational drug, whichever is longer
* History of receiving murine or human-murine recombination products, such as G250, BE-8, and other monoclonal antibodies. (Note: Prior rituximab treatment is not an exclusion criterion)
* Serious concurrent illness or significant cardiac disease characterized by significant ischemic coronary disease or congestive heart failure
* Known human immunodeficiency virus seropositivity, acquired immunodeficiency syndome, hepatitis C or active hepatitis B infection. For Cohort 7, known human herpesvirus-8 seropositivity
* Presence of a transplanted solid organ (with the exception of a corneal transplant more than 3 months prior to screening) or having received an allogeneic bone marrow transplant or an allogeneic peripheral blood stem cell transplant

Primary outcomes:
measure: Number of Patients With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 3 years after the last administration of study medication
measure: Serum Concentration of CNTO 328
timeFrame: Up to Day 71
Secondary outcomes:
measure: Pharmacodynamics of CNTO 328
timeFrame: Up to Day 71
measure: Plasma antibodies to CNTO 328
timeFrame: Up to Week 24
measure: Number of participants with Castleman's disease who achieved tumor response
timeFrame: Screening phase (4 weeks before administration of study medication), Day 36, and Day 57
measure: Number of participants with multiple myeloma who achieved disease response
timeFrame: Screening phase (4 weeks before administration of study medication), Day 36, and Day 57
measure: Number of participants with B-cell non-Hodgkin's lymphoma and multiple myeloma who achieved clinical benefit (CB)
timeFrame: Up to Day 71
measure: Number of participants with Castleman's disease who achieved clinical benefit
timeFrame: Up to Day 71
measure: Number of participants with B-cell non-Hodgkin's lymphoma who achieved disease response
timeFrame: Screening phase (4 weeks before administration of study medication), Day 36, and Day 57
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Box 302
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References: