A single-arm, international, multi-center trial of HuMax-CD20, a fully human monoclonal anti-CD20 antibody, in patients with B-cell Chronic Lymphocytic Leukemia who have failed fludarabine and alemtuzumab - HuMax-CD20 in B-CLL patients failing fludarabine and alemtuzumab

• Conditions: B-cell Chronic Lymphocytic Leukemia; MedDRA version: 7.0Level: LLTClassification code 10008959

• Registration Number: EUCTR2005-006163-31-DE
• Lead Sponsor: Glaxo SmithKline Research and Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-04-07
• Last Update Posted: 11 February 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 225

Inclusion Criteria

1) Tumor cell phenotype consistent with B-CLL:
• CD5
• CD20
• CD23
2) Patients with active B-CLL and with an indication for treatment, defined as presenting
one of the following conditions as defined by the NCIWG guidelines (1):
a. evidence of progressive marrow failure as manifested by development of, or
worsening of anemia or thrombocytopenia; or,
b. massive (= 6 cm below the left costal margin) or progressive splenomegaly; or,
c. massive nodal clusters (= 10 cm in longest diameter) or progressive
lymphadenopathy; or,
d. progressive lymphocytosis with an increase of > 50% over a two month period or an
anticipated doubling time < 6 months; or,
e. any one of the following disease related conditions:
i. 10% or greater weight loss within the previous six months, or
ii. fevers = 100.5°F (38.0°C) for = 2 weeks without evidence of infection, or
iii. night sweats without evidence of infection.
3) Failing at least one fludarabine-containing treatment regimen (a minimal of at least 2
cycles), defined as:
a. Refractory to one fludarabine-containing treatment regimen, defined as:
i. failure to achieve at least PR to at least one fludarabine-containing treatment
regimen; or,
ii. disease progression while on a fludarabine-containing treatment regimen; or,
iii. disease progression in responders within 6 months of the last dose of a
fludarabine-containing treatment regimen
4) Failing at least one alemtuzumab-containing treatment regimen (a minimal of at least 12
administrations), defined as:
a. Refractory to one alemtuzumab-containing treatment regimen, defined as:
i. failure to achieve at least PR to at least one alemtuzumab-containing
treatment regimen; or,
ii. disease progression while on a alemtuzumab-containing treatment regimen;
or,
iii. disease progression in responders within 6 months of the last dose of a
alemtuzumab-containing treatment regimen
b. Considered inappropriate for treatment with alemtuzumab due to lymphadenopathy
with at least one lymph node > 5 cm and requiring therapy
5) ECOG Performance Status of 0, 1 or 2
6) Life expectancy of at least 6 months
7) Age = 18 years
8) Following receipt of verbal and written information about the study, the patient must
provide signed informed consent before any study related activity is carried out

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Previous treatment with alemtuzumab within 6 weeks prior to Visit 2
2) Previous autologous stem cell transplantation within 6 months prior to Visit 2
3) Allogeneic stem cell transplantation
4) Radioimmunotherapy
5) Received any of the following treatments within 4 weeks prior to Visit 2:
• Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues,
monoclonal antibodies)
• Glucocorticoid unless given in doses equivalent to = 10 mg of prednisolone
/day
• Leukapheresis
6) Patients previously treated with HuMax-CD20
7) Known transformation to more aggressive B-cell malignancies (e.g. large B-cell
Lymphoma, Richter’s Syndrome, or PLL).
8) Known CNS involvement of B-CLL
9) Past or current malignancy, except for:
• Cervical carcinoma Stage 1B or less
• Non-invasive basal cell and squamous cell skin carcinoma
• Malignant melanoma with a complete response of a duration of > 10 years
• Other cancer diagnoses with a complete response of a duration of > 5 years
10) Chronic or ongoing active infectious disease requiring systemic treatment such as, but
not limited to, chronic renal infection, chronic chest infection with bronchiectasis,
tuberculosis and active hepatitis C
11) Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within six months from Visit 1, congestive heart failure, and arrhythmia
requiring therapy, with the exception of extra systoles or minor conduction abnormalities
12) Significant concurrent, uncontrolled medical condition including, but not limited to,
renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological,
cerebral or psychiatric disease
13) History of significant cerebrovascular disease
14) Known HIV positive
15) Positive serology for hepatitis B, defined as a positive test for HBsAg and/or a
combination of a positive test for anti-HBs and anti-HBc
16) Removed by Amendment 2
17) Known or suspected hypersensitivity to components of investigational product
18) Patients with pleural effusion or ascites of significant degree, defined as detectable by
physical examination
19) ECOG Performance Status of 3 or 4
20) Life expectancy less than 6 months
21) Patients who have received treatment with any non-marketed drug substance or
experimental therapy within 4 weeks prior to Visit 2
22) Current participation in any other interventional clinical study
23) Patients known or suspected of not being able to comply with a study protocol (e.g. due
to alcoholism, drug dependency or psychological disorder)
24) Breast feeding women or women with a positive pregnancy test at Visit 1
25) Women of childbearing potential not willing to use adequate contraception during study
and one year after last dose of HuMax-CD20. Adequate contraception is defined as
hormonal birth control or intrauterine device. For patients in the USA the use of a double barrier method is also considered adequate.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of HuMax-CD20 in patients with B-cell Chronic Lymphocytic Leukemia (B-CLL) who have failed fludarabine and alemtuzumab;Secondary Objective: •To determine the safety of HuMax-CD20<br>•To determine the host immune response to HuMax-CD20<br>•To determine the pharmacokinetic profile of HuMax-CD20<br><br>;Primary end point(s): Objective response as measured over a 24 week period from start of treatment assessed by an Independent endpoints Review Committee (IRC), according to the NCIWG guidelines.