PHASE II TRIAL TO EVALUATE THE EFFICACY OF OBINUTUZUMAB (RO5072759) + BENDAMUSTINE TREATMENT IN PATIENTS WITH REFRACTORY OR RELAPSED CHRONIC LYMPHOCYTIC LEUKEMIA

Phase 1

• Conditions: Chronic lymphocytic leukemia; MedDRA version: 16.1 Level: LLT Classification code 10008977 Term: Chronic lymphocytic leukemia recurrent System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003388-79-ES
• Lead Sponsor: Roche Farma, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-12-05
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 72

Inclusion Criteria

1.Age 18 years or older
2.Have documented CD20+ B-CLL according to NCI criteria (see Appendix 2)
3.Active disease meeting at least 1 of the following IWCLL 2008 criteria for requiring treatment:
a)Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (Hgb < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/µL)
b)Massive (i.e. at least 6 cm bellow the left costal margin), progressive or symptomatic splenomegaly
c)Massive nodes (i.e. at least 10 cm in the longest diameter), progressive or symptomatic lymphadenopathy
d)Progressive lymphocytosis with an increase of more than 50% over a 2-month period or a lymphocyte doubling time (LDT) of less than 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of 2 weeks over an observation period of 2-3 months. In patients with initial blood lymphocyte counts of less than 30 x 109/L (30,000/µL), LDT should not be used as a single parameter to define indication for the treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded,
e)Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
f)Constitutional symptoms documented in the patient´s chart with supportive objective measures, as appropriate, defined as one or more of the following disease-related symptoms or signs:
i.Unintentional weight loss > 10% within the previous 6 months prior to Screening
ii.Fever higher than 38.0ºC for 2 or more weeks prior to Screening without evidence of infection
iii.Night sweats for more than 1 month prior to Screening without evidence of infection.
4.Refractory CLL (i.e. treatment failure or progression within 6 months of treatment) or relapse CLL (i.e. patient who met criteria for CR or PR, but progressed beyond 6 months post-treatment).
5.At least 1 prior purine analogue or bendamustine containing therapy
6.Creatinine clearance =30ml/min or both
7.Hemoglobin > 9 g/dL; absolute neutrophil count (ANC) = 1.5 x 109/L and platelets (Plt) = 75 x 109/L unless cytopenia is caused by the underlying disease, i.e. no evidence of additional bone marrow dysfunction (e.g. myelodysplastic syndrome [MDS])
8.Life expectancy >6-8 months
9.Able and willing to provide written informed consent and to comply with the study protocol procedures

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 43
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 29

Exclusion Criteria

1.Prior Alogenic Bone Marrow Transplant
2.= 3 previous lines of chemotherapy and/or immunotherapy for the CLL.
3.Previous obinutuzumab-containing regimen.
4.Refractory CLL to bendamustine treatment (i.e. treatment failure or progression within 6 months of bendamustine-containing regimen).
5.Transformation of CLL to aggressive NHL (Richter’s transformation)
6.Active haemolytic anaemia
7.Inadequate liver function: NCICTC Grade 3 liver function tests (AST, ALT >5 x ULN for >2 weeks; Bilirubin >3 x ULN) unless due to underlying disease.
8.History of other malignancy which could affect compliance with the protocol or interpretation of results. Patients with a history of malignancy that has been treated but not with curative intent will be excluded, unless the malignancy has been in remission without treatment for = 2 years prior to enrolment. Patients with a history of adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent are eligible.
9.Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, severe arrhythmia, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm).
10.Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis.
11.Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle 1, unless administered for indications other than lymphoma at a dose equivalent to = 30 mg/day prednisone
12.Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 4 weeks prior to the start of Cycle 1.
13.Patients with known infection with Human immunodeficiency virus (HIV) or Human T Cell Leukemia Virus 1 (HTLV-1).
14.Positive hepatitis serology:
a)Hepatitis B (HBV): Patients with positive serology for Hepatitis B defined as positivity for Hepatitis B surface antigen (HBsAg) or anti Hepatitis B core antibody (anti-HBc). Patients positive for anti-HBc may be included if Hepatitis B viral DNA is not detectable.
b)Hepatitis C (HCV): Patients with positive Hepatitis C serology unless HCV (RNA) is confirmed negative.
15.History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
16.Known sensitivity or allergy to murine products.
17.Known hypersensitivity to any of the study drugs
18.Women who are pregnant or lactating
19.Fertile men or women of childbearing potential unless: (1) surgically sterile or = 2 years after the onset of me

Study & Design

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