GIMEMA CLL0809 Study (BendOfa)

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01244451
• Date of registration: 18/11/2010
• Primary sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Public title: GIMEMA CLL0809 Study (BendOfa) BendOfa
• Scientific title: A Single-Arm Multi-Center Trial of Bendamustine Given With Ofatumumab (BendOfa) in Patients With Refractory or Relapsed Chronic Lymphocytic Leukemia (CLL). EudraCT Number 2009-017663-42. GIMEMA CLL0809 Protocol
• Date of first enrolment: December 2010
• Target sample size: 49
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT01244451
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Italy

Contacts

• Name: Agostino Cortelezzi, Pr.
• Affiliation: Direzione Scientifica - Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with CLL relapsing after an initial response (CR, PR = 6 months) following
no more than two prior treatment lines; or

- Patients with CLL refractory (SD, PD or CR/PR < 6 months) following no more than two
prior treatment lines

- Patients requiring treatment according to 2008 revised IWCLL guidelines

- No more than 2 prior treatment lines

- Age older or equal to 18 years

- No active malignancies during the previous 5 years, with the exception of currently
treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of
any origin

- No prior treatment with conventional chemotherapy within the prior 4 weeks and with
monoclonal antibodies within the prior 16 weeks

- ECOG performance status of =2 at study entry

- Laboratory test results within these ranges:

Serum creatinine = 2 x UNL Creatinine clearance = 50 ml/min (Cockcroft and Gault formula)
Total bilirubin = 2 x UNL (with exception of patients with Gilbert's syndrome) AST (SGOT)
and ALT (SGPT) = 2 x UNL non attributable to CLL AST (SGOT) and ALT (SGPT) = 10 x UNL
attributable to CLL

- Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test prior to therapy and must agree to abstain from breastfeeding during
study participation and for at least one year after discontinuation from the study.

- Signed written informed consent according to IGH/EU/GCP and Italian laws.

Exclusion Criteria:

- Concurrent use of other anti-cancer agents

- Use of any other experimental drug or therapy within 28 days of baseline

- Positive direct antiglobulin test (DAT) with clinical and laboratory signs of
hemolysis and/or autoimmune thrombocytopenia

- Known transformation of CLL

- Known CNS involvement of CLL

- Known positivity for HIV or active HCV and HBV hepatitis.

- Active bacterial, viral or fungal infection requiring systemic anti-viral, antibiotic
or anti-fungal therapy.

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.

- Subjects who have current active hepatic or biliary disease (with exception of
patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver
disease per investigator assessment)

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she was to participate in the study or confounds
the ability to interpret data from the study Concurrent use of other anti-cancer
agents

- Use of any other experimental drug or therapy within 28 days of baseline

- Positive direct antiglobulin test (DAT) with clinical and laboratory signs of
hemolysis and/or autoimmune thrombocytopenia

- Known transformation of CLL

- Known CNS involvement of CLL

- Known positivity for HIV or active HCV and HBV hepatitis.

- Active bacterial, viral or fungal infection requiring systemic anti-viral, antibiotic
or anti-fungal therapy.

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.

- Subjects who have current active hepatic or biliary disease (with exception of
patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver
disease per investigator assessment)

- Concurrent use of other anti-cancer agents

- Use of any other experimental drug or therapy within 28 days of baseline

- Positive direct antiglobulin test (DAT) with clinical and laboratory signs of
hemolysis and/or autoimmune thrombocytopenia

- Known transformation of CLL

- Known CNS involvement of CLL

- Known positivity for HIV or active HCV and HBV hepatitis.

- Active bacterial, viral or fungal infection requiring systemic anti-viral, antibiotic
or anti-fungal therapy.

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.

- Subjects who have current active hepatic or biliary disease (with exception of
patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver
disease per investigator assessment)

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she was to participate in the study or confounds
the ability to interpret data from the study Any condition, including the presence of
laboratory abnormalities, which places the subject at unacceptable risk if he/she was
to participate in the study or confounds the ability to interpret data from the study



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Patients With CLL Refractory (SD, PD or CR/PR < 6 Months) Following no More Than Two Prior Treatment Lines

Patients With CLL Relapsing After an Initial Response (CR, PR = 6 Months) Following no More Than Two Prior Treatment Lines; or

Intervention(s)

Drug: Bendamustine

Drug: Ofatumumab

Primary Outcome(s)

Overall Response Rate (ORR, percentage of patients who achieve CR, CRi, MRD negative CR [cytometric and molecular], PR) [Time Frame: After 8 monhts from therapy start (6 months of treatment plus 2 months from the last course to response evaluation)]

Secondary Outcome(s)

Assess the relationship between ORR, PFS and CIRS total score at screening. [Time Frame: 32 months from treatment start]

Duration of response [Time Frame: Defined as the time to achievement ORR to either progression/relapse or death without progression or last follow-up in case of no such failure occurs (censoring).]

Overall survival [Time Frame: Defined as the time interval between the date of first BendOfa treatment dose - induction phase and the date of death for any cause.]

Progression free survival [Time Frame: From the date of first BendOfa treatment dose - induction phase - until the date of the first documentation of progressive disease or until death (whatever the cause), whichever occurs first.]

Rate of CR, CRi, MRD negative CR [Time Frame: After 8 monhts from therapy start (6 months of treatment plus 2 months from the last course to response evaluation)]

Response rate, duration of response, OS and TTNT according to the following biologic features of CLL: IgVH mutational status, FISH abnormalities (6q-; 11q-; +12; 13q-; 17p-), TP53 mutation, CD38 expression, ZAP70 expression. [Time Frame: 32 months from treatment start]

Time to new treatment [Time Frame: From the date of last BendOfa treatment dose until date of a new treatment received for CLL, where death occurred before the new treatment will be considered as competing risk.]

Time to progression (TTP) [Time Frame: From the date of first BendOfa treatment dose - induction phase - until the date of the first documentation of progressive disease using the cumulative incidence method.]

Toxicity according to CTCAE version 4.0 [Time Frame: At 44 months from treatment start.]

Secondary ID(s)

CLL0809

Source(s) of Monetary Support

Please refer to primary and secondary sponsors