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-NL
• Lead Sponsor: Genmab A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-05-10
• Last Update Posted: 25 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

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, defined as:
a. Refractory to one fludarabine-containing treatment regimen, defined as; or
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
b. Intolerant to fludarabine, defined as:
i. Discontinuation of therapy due to side effects/toxicity whether or not response occurred; or,
ii. Ineligible to treatment with fludarabine due to history of previous fludarabine-induced autoimmune hemolytic anemia or autoimmune thrombocytopenia

4) Failing at least one alemtuzumab-containing treatment regimen, defined as:
a. Refractory to one alemtuzumab-containing treatment regimen, defined as; or
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.Intolerant to alemtuzumab, defined as:
i. Discontinuation of therapy due to side effects/toxicity whether or not response occurred; or,
ii. Ineligible to treatment with alemtuzumab due to concurrent medical conditions, such as:
1. previous pneumocystis carinii pneumonia (PCP)
2. history of other severe opportunistic infections
3. repeated grade 3 or 4 infections of other types
4. lympadenopathy with at least one lymph node > 5 cm causing symptoms or compression and requiring therapy

5) ECOG Performance Status of 0, 1 or 2

6) Life expectancy of at least 4 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 1

2) Previous autologous stem cell transplantation within 6 months prior to Visit 1

3) Allogeneic stem cell transplantation

4) Radioimmunotherapy

5)Received any of the following treatments within 4 weeks prior to Visit 1: 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 or suspected Richter transformation of B-CLL

8) Known or suspected 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 or suspected HIV positive

15) Positive serology for hepatitis B, unless vaccination against Hepatitis B can be documented

16) Screening laboratory values:
•platelets < 25 x 109/L
•creatinine > 1.5 times upper normal limit (unless normal creatinine clearance)
•total bilirubin > 1.5 times upper normal limit (unless due to liver involvement of B-CLL)
•ALT > 2.5 times upper normal limit (unless due to liver involvement of B-CLL)
•alkaline phosphatase > 2.5 times upper normal limit (unless due to liver involvement of B-CLL)

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 4 months

21) Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 1

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