Patients With CLL Relapsing After an Initial Response (CR, PR ≥ 6 Months) Following no More Than Two Prior Treatment Lines; orPhase 2BendOfaNCT01244451
GIMEMA CLL0809 Study (BendOfa)
A Phase 2 study testing Ofatumumab and Bendamustine in people with Patients With CLL Relapsing After an Initial Response (CR, PR ≥ 6 Months) Following no More Than Two Prior Treatment Lines; or and Patients With CLL Refractory (SD, PD or CR/PR < 6 Months) Following no More Than Two Prior Treatment Lines, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 32 sites in Italy.
Trial summary
In the last ten years there have been significant developments in CLL treatment. The advent of fludarabine, rituximab and the association of chemo-immunotherapy have substantially increased overall response rate, CR rate, time to progression and may also have an impact on overall survival. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- 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
- What is being tested?
- Ofatumumab and Bendamustine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 32 sitesItaly
- Study dates
- Dec 2010to Jul 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Female subjects of childbearing potential(FCBP) must:
- Understands the potential teratogenic risk to the unborn child and the need for effective contraception;
- Be capable of complying with effective contraceptive measures.
- Be informed and understand the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy.
- Understand the need to commence the study treatment as soon as study drug is dispensed following a negative pregnancy test.
- Understand the need and accepts to undergo pregnancy testing based on the frequency outlined in this protocol.
- Females of childbearing potential (FCBP) enrolled in this protocol must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) before starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 28 days after study treatment discontinuation.
- The two methods of reliable contraception must include one highly effective method and one additional effective (barrier) method. FCBP must be referred to a qualified provider of contraceptive methods if needed. The following are examples of highly effective and additional effective methods of contraception:
- Highly effective methods:
- Intrauterine device (IUD)
- Hormonal (birth control pills, injections, implants)
- Tubal ligation
- Partner's vasectomy
- Additional effective methods:
- Male condom
- Diaphragm
- Cervical Cap
- Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered particularly in patients with neutropenia.
- Pregnancy testing.
- FCBP must have two negative pregnancy tests prior to starting study drug.
- FCBP must agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
- Females must agree to abstain from breastfeeding during study participation and for at least 28 days after study drug discontinuation.
- Male patients must:
- Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female or a female of childbearing potential.
- Must practice complete abstinence or agree to use a prophylactic during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 6 months following study drug discontinuation, even if he has undergone a successful vasectomy.
- If pregnancy or a positive pregnancy test does occur in the partner of a male study patient during study participation, the investigator must be notified immediately.
- Female and male patients
- should be instructed never to give this medicinal product to another person and to return any unused capsules to the study doctor at the end of treatment.
- Should not donate blood during therapy and for at least 28 days following discontinuation of study drug.
- Male patients should not donate semen or sperm while participating in the study, during dose interruptions and for at least 6 months following study drug discontinuation
- Signed written informed consent according to IGH/EU/GCP and Italian laws.
Who cannot join
- 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.
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- 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)
- Pregnant or Lactating Females.
- 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
Trial locations and contacts
32 sites in 1 country.
32 sites in 1 country
Italy32 sites
Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"
Ascoli Piceno
Unità Operativa Ematologia 1 - Università degli Studi di Bari
Bari, 70010
Ist.Ematologia e Oncologia Medica L.e A. Seragnoli
Bologna
Azienda Sanitaria di Bolzano - Ospedale Centrale - Ematologia e Centro TMO
Bolzano
Azienda ASL di Cagliari
Cagliari, 9121
U.O.C. di Onco-Ematologia - Centro di Ricerca e Formazione ad Alta tecnologia nelle Scienze Biomediche
Campobasso
Ospedale Ferrarotto
Catania, 95124
Azienda Ospedaliera Pugliese Ciaccio
Catanzaro, 88100
U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza
Cosenza
Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
Ferrara, 44100
Policlinico di Careggi, Università delgi studi di Firenze
Florence
Clinica Ematologica - Università degli Studi
Genova
ASL Le1 P.O. Vito Fazzi - U.O. di Ematologia
Lecce, 73100
Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
Messina
Messina Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"
Messina
Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
Milan
Unità Trapianto di Midollo Ist. Nazionale Tumori
Milan
Sez. di medicina Interna Oncologia ed Ematologia
Modena
Ospedale San Gennaro - ASL Napoli 1
Naples, 80143
U.O. Ematologia Clinica - Azienda USL di Pescara
Pescara
Dipartimento Emato-Oncologia A.O. "Bianchi-Melacrino-Morelli"
Reggio Calabria
S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
Roma
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
Roma
Università degli Studi - Policlinico di Tor Vergata
Roma
Università degli studi di Roma La Cattolica
Roma
Ospedale S.Eugenio
Rome, 00144
Ospedale Casa Sollievo della sofferenza
San Giovanni Rotondo
U.O. Ematologia, Azienda Ospedaliera Universitaria Senese
Siena, 53100
SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni
Terni
Div. di Ematologia "Molinette" Osp. Maggiore S. G. Battista
Torino
Clinica Ematologica - Policlinico Universitario
Udine
Policlinico G.B. Rossi
Verona, 37134
About this study
Official 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
In the last ten years there have been significant developments in CLL treatment. The advent of fludarabine, rituximab and the association of chemo-immunotherapy have substantially increased overall response rate, CR rate, time to progression and may also have an impact on overall survival.
Even though, CLL remains incurable and all patients eventually relapse and progressively become resistant to treatment. The development of an effective therapy that is not cross-resistant with the ones currently available as front-line treatment, is one of the clinical unmet needs within CLL.
Read more
BendOfa is a non comparative phase II trial designed to determine the therapeutic benefit of bendamustine given together to ofatumumab in relapsed or resistant patients with CLL.
Bendamustine is approved by FDA for CLL treatment, it is an hybrid drug with alkylating agents and purine analogue properties that may lack of cross resistance with fludarabine. It was utilized in CLL as a single agent and its association with rituximab is currently under clinical investigation.
Ofatumumab is a new fully human anti-CD20 monoclonal antibody with high in vitro efficacy on CD20 low-expressing CLL cells. An early report showed that ofatumumab in single therapy is effective in highly pre-treated refractory CLL patients.
Both drugs were generally well tolerated without unexpected untoward toxicity. On the basis of these data, bendamustine and ofatumumab could be a new effective and well tolerated combination for patients with relapsed and refractory CLL.
- Conditions
- 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
- Being tested
- Ofatumumab, Bendamustine
- Keywords
- CLL, relapsed, refractory, Bendamustine, Ofatumumab
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OfatumumabDrug
Ofatumumab will be administered at the dose of 300 mg IV D1 and 1000 mg IV D8 1st course; 1000 mg IV D1, 2nd -6th courses.
BendamustineDrug
Bendamustine will be infused at the doses of 70 mg/m2 IV on days D1 and D2 of each course.
| Study group | Role | What they receive |
|---|---|---|
| Bendofa | Experimental | Bendamustine + Ofatumumab Receives: Drug: Ofatumumab; Drug: Bendamustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Contributing to the Overall Response Rate
Patients response to treatment will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy and radiographic evaluation according to the revised IWCLL 2008 criteria.
Measured: After 8 months from therapy start (6 months of treatment plus 2 months from the last course to response evaluation)
Secondary outcomes (3)
Toxicity According to CTCAE Version 4.0
Number of patients experiencing 3 or >3 AEs (both hematological and not hematological)
Measured: At 44 months from treatment start.
Progression Free Survival
Patients still alive and known to be progression-free will be censored at the moment of last follow-up. Patients disease progression will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy and radiographic evaluation according to the revised IWCLL 2008 criteria.
Measured: Up to 32 months: 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.
Overall Survival
Patients still alive will be censored at the moment of last follow-up.
Measured: At 44 months from treatment start.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2010 (estimated)
- Study startDec 2010
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Patients With CLL Relapsing After an Initial Response (CR, PR ≥ 6 Months) Following no More Than Two Prior Treatment Lines; orStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Agostino Cortelezzi, Pr., Principal investigator, Direzione Scientifica - Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01244451
- Sponsor's protocol ID
- CLL0809
- Acronym
- BendOfa
- Status last verified
- Jan 2019
- First submitted
- 18 Nov 2010
- Last updated
- 25 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01244451
- Acronym / sponsor ID
- BendOfa / CLL0809
- Conditions
- 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
- Keywords
- CLL, relapsed, refractory, Bendamustine, Ofatumumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'AdultoUniversity, hospital or other
- Study start
- Dec 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 19 Nov 2010 (estimated)
- Results
- Posted 25 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the last ten years there have been significant developments in CLL treatment. The advent of fludarabine, rituximab and the association of chemo-immunotherapy have substantially increased overall response rate, CR rate, time to progression and may also have an impact on overall survival.
Even though, CLL remains incurable and all patients eventually relapse and progressively become resistant to treatment. The development of an effective therapy that is not cross-resistant with the ones currently available as front-line treatment, is one of the clinical unmet needs within CLL.
BendOfa is a non comparative phase II trial designed to determine the therapeutic benefit of bendamustine given together to ofatumumab in relapsed or resistant patients with CLL.
Bendamustine is approved by FDA for CLL treatment, it is an hybrid drug with alkylating agents and purine analogue properties that may lack of cross resistance with fludarabine. It was utilized in CLL as a single agent and its association with rituximab is currently under clinical investigation.
Ofatumumab is a new fully human anti-CD20 monoclonal antibody with high in vitro efficacy on CD20 low-expressing CLL cells. An early report showed that ofatumumab in single therapy is effective in highly pre-treated refractory CLL patients.
Both drugs were generally well tolerated without unexpected untoward toxicity. On the basis of these data, bendamustine and ofatumumab could be a new effective and well tolerated combination for patients with relapsed and refractory CLL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bendofa | Experimental | Drug: Ofatumumab, Drug: BendamustineBendamustine + Ofatumumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (41 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OfatumumabOfatumumab will be administered at the dose of 300 mg IV D1 and 1000 mg IV D8 1st course; 1000 mg IV D1, 2nd -6th courses. | Drug | Bendofa |
| BendamustineBendamustine will be infused at the doses of 70 mg/m2 IV on days D1 and D2 of each course. | Drug | Bendofa |
Primary outcome
Number of Participants Contributing to the Overall Response Rate
Time frame: After 8 months from therapy start (6 months of treatment plus 2 months from the last course to response evaluation)
Patients response to treatment will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy and radiographic evaluation according to the revised IWCLL 2008 criteria.
3 secondary outcomes
Toxicity According to CTCAE Version 4.0
Time frame: At 44 months from treatment start.
Progression Free Survival
Time frame: Up to 32 months: 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.
Overall Survival
Time frame: At 44 months from treatment start.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- GIMEMA Foundation WebsiteLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Agostino Cortelezzi, Pr. principal investigator
Direzione Scientifica - Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
32 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ofatumumab and Bendamustine in people with Patients With CLL Relapsing After an Initial Response (CR, PR ≥ 6 Months) Following no More Than Two Prior Treatment Lines; or and Patients With CLL Refractory (SD, PD or CR/PR < 6 Months) Following no More Than Two Prior Treatment Lines, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 32 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 41 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Contributing to the Overall Response Rate (time frame: After 8 months from therapy start (6 months of treatment plus 2 months from the last course to response evaluation)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2019; AzTrials last refreshed its copy on 27 Oct 2026.