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Study Summary
No. 2005-0025:.......Leukemia......Susan O'Brien......Leukemia
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Study Summary Title
Study Summary
Number:
2005-0025
Study Title:An open-label, multi-center, Phase I/II study of anti-CD40 monoclonal antibody HCD122 (CHIR-12.12) administered intravenously to patients with advanced chronic lymphocytic leukemia that is refractory or relapsed after at least one previous fludarabine-containing chemotherapy regimen
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Physician New Patient Referral
Name:Susan O'BrienPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-7543
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:N/A
Phase of Study:Phase I/Phase IIReturn
Visit:
Weekly for weeks 1, 2, 3, 4, 5, 6, then week 7, 9, 12, 16, then every 8 weeks
until disease
progression.
Treatment
Agents:
HCD122Home Care:None
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
No hospitalization required.
Description/
Intervention:
The goal of this clinical research study is to learn about the safety of HCD122
(CHIR-12.12) when it is given by vein to patients with CLL. In addition, blood
levels of the drug at various time points will be measured and response to
treatment will be evaluated.
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Study Objectives / Outcomes
Dose Excalation Phase

Primary Objective:
  • To determine the maximum tolerated dose (MTD) of HCD122 (CHIR-12.12) in patients with
relapsed or refractory CLL after at least one previous fludarabine-containing chemotherapy
regimen.

Secondary Objectives:
  • To characterize safety, tolerability, and pharmacokinetics of HCD122 (CHIR-12.12)
  • To characterize peripheral blood CD40 occupancy on CD5/CD19 (CLL) cells and CD5/CD19
cell depletion activity (pharmacodynamics) of HCD122 (CHIR-12.12)
  • To assess preliminary anti-tumor activity of HCD122 (CHIR-12.12)

Two-arm, two-stage dose expansion phase

Primary objective:

Arm 1 To assess tumor response at the MTD in dose expansion patients who have fludarabine-
relapsed CLL.

Arm 2 To assess tumor response at the MTD in dose expansion patients who have fludarabine-
refractory CLL.

Secondary objectives:
  • To characterize the safety, tolerability, and pharmacokinetics of HCD122 (CHIR-12.12) at the MTD.
  • To characterize peripheral blood CD40 occupancy on CD5/CD19 (CLL) cells and CD5/CD19 cell
    depletion activity (pharmacodynamics) of HCD122 (CHIR-12.12) at the MTD.

Dose expansion and dose escalation

Exploratory objectives:
  • To assay potential biomarkers of HCD122 (CHIR-12.12) activity and correlate them
with pharmacokinetic parameters and antitumor effects following HCD122 (CHIR-12.12)
infusion.
  • To assess potential correlations between disease prognosis markers (e.g., gene
rearrangement FISH panel or ZAP70) and pharmacokinetic or anti-tumor effects following
HCD122 (CHIR-12.12) infusion.
  • In consenting patients, pharmacogenetic analysis of blood to identify potential
correlations between genetic polymorphisms and pharmacokinetic or antitumor effects
following HCD122 (CHIR-12.12) infusion.
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Study Status Information
Study Activation / Registration Date:03/16/2005
IRB Review and Approval Date:02/16/2005
Study Type:Therapeutic
Recruitment Status:Terminated
Projected Accrual:116
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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) Diagnosed with histopathologically confirmed CLL

2) Refractory or relapsed disease after treatment with at least one previous fludarabine-containing chemotherapy regimen

3) Rai stage III or IV, or stage I or II with indication for treatment defined, as follows, by the (NCIWG) Guidelines: (1) massive or progressive splenomegaly; OR (2) massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR (3) Grade 2 or 3 fatigue; or fever >/= 100.5 degreesF or night sweats for greater than 2 weeks without documented infection; or presence of weight loss >/= 10% over the preceding 6 months; OR (4) progressive lymphocytosis with an increase in lymphocyte count of >/= 50% over a 2-month period or an anticipated doubling time of less than 6 months

4) Willing and able to sign an informed consent form

5) Male or female, age >/= 18 years

6) Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0, 1, or 2

7) Life expectancy greater than 3 months

8) Laboratory criteria: (1) Platelet count >/= 50 x 10^3/µL (must not have had platelet transfusion within previous 10 days); (2) Hemoglobin >/= 8.0 g/dL (may have been transfused); (3) Serum creatinine </= 2.0 mg/dL; (4) AST </= 2x ULN; (5) ALT </= 2x ULN; (6) Total bilirubin < 1.5 mg/dL; (7) Alkaline phosphatase </= ULN; (8) Uric acid </= 8 mg/dL; (9) Hepatitis B antigen negative (10) Serum amylase </= ULN (11) Serum lipase </= ULN (12) Fasting serum triglycerides </= 500 mg/dL

9) Patients must have discontinued previous anticancer or investigational therapy for at least 30 days and have recovered fully from the toxic effects of that treatment (for antibody-related therapy see exclusion criteria below):

10) A period of >/= 30 days must have elapsed after major surgery and the patient must have fully recovered after such surgery.

11) For dose expansion phase, pts will be enrolled in 2 arms (fludarabine-relapsed versus fludarabine-refractory): Arm1-fludarabine-relapsed-2-stage design-Pts who had recurrence of disease after achieving PR or CR to any prior fludarabine-containing regimen for at least 6 mos after last dose of fludarabine. Arm2-fludarabine-refractory-2 stage design-Pts who failed to achieve PR or CR to at least 1 fludarabine-containing regimen; had disease progression while on fludarabine treatment; responders (CR or PR) who showed disease progression w/i 6 mos of the last dose of fludarabine.

Exclusion Criteria:1) Patients received antibody therapy within the time period as described below, and/or have not fully recovered from the toxic effects of that treatment: (1) Alemtuzumab (Campath®) within 6 months prior to the first dose of HCD122 (CHIR-12.12), (2) Rituximab (Rituxan®) within 60 days prior to the first dose of HCD122 (CHIR-12.12), (3) Any other monoclonal antibody within 90 days prior to the first dose of HCD122 (CHIR-12.12)

2) History of another primary malignancy that is currently clinically significant, has the potential for metastases or currently requires active intervention

3) Impaired cardiac function or clinically significant cardiac disease, including any one of the following: (1) New York Heart Association Class III or IV cardiac disease, including preexisting arrhythmia, congestive heart failure, or cardiomyopathy (2) Angina pectoris </= 3 months prior to starting study drug (3) Acute MI </= 3 months prior to starting study drug (4) Other clinically significant heart disease (e.g., uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)

4) Clinically significant pulmonary dysfunction requiring oxygen therapy; for any patient with a history of serious pulmonary disease, FEV(subscript)1 and DL (subscript)CO must be > 55% predicted within 8 weeks of enrollment

5) History of pulmonary embolism

6) History of deep vein or other thrombosis with the exception of catheter thrombosis; patients with an intravenous catheter must be treated with a low dose prophylactic anticoagulant to prevent catheter thrombosis

7) History of active infection (viral, bacterial, or fungal) requiring systemic therapy within 4 weeks of enrollment

8) Prior allogeneic stem cell transplant

9) Active autoimmune disease requiring imunosuppressive therapy

10) Known positive serology for human immunodeficiency virus (HIV)

11) Known current drug or alcohol abuse

12) Other severe, acute, or chronic medical or phychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for this study

13) Prior anaphylactic reaction to human immunoglobulin administration

14) History of pancreatic disease (e.g., acute or chronic pancreatitis, etc.) or any surgery of the pancreas

15) Women of child-bearing potential (WCBP) who are pregnant or breast feeding. WCBP defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months must have a negative serum pregnancy test </= 72 hours prior to starting study treatment. In addition, all sexually active WCBP and male patients must agree to use adequate contraceptive methods throughout the study.

16) Any abnormality on the baseline CT scan that potentially is associated with an increased risk of developing a pancreatitis or an increase in serum amylase and/or lipase (e.g., gallbladder stones).

17) Cystic fibrosis or any other risk factors that may contribute to the development of pancreatitis.

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Links
Registration Number: NCT00108108
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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