GIMEMA CLL0809 Study (BendOfa) (BendOfa)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01244451
Recruitment Status : Completed
First Posted : November 19, 2010
Last Update Posted : January 30, 2015
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Brief 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.

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.

Condition or disease Intervention/treatment Phase
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 Drug: Ofatumumab Drug: Bendamustine Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : December 2010
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Intervention Details:
    Drug: Ofatumumab
    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.
    Drug: Bendamustine
    Bendamustine will be infused at the doses of 70 mg/m2 IV on days D1 and D2 of each course.

Primary Outcome Measures :
  1. 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 Measures :
  1. 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) ]
  2. Toxicity according to CTCAE version 4.0 [ Time Frame: At 44 months from treatment start. ]
  3. 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. ]
    Where death without signs of disease progression will be considered as competing risk. Patients still alive and known to be progression free will be censored at the moment of last follow-up.

  4. 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. ]
    Patients still alive and known to be progression free will be censored at the moment of last follow-up.

  5. 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. ]
    Patients still alive without receiving a new treatment will be censored at the time of the last follow-up.

  6. 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. ]
    Patients still alive will be censored at the moment of last follow-up.

  7. 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). ]
  8. 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 ]
  9. Assess the relationship between ORR, PFS and CIRS total score at screening. [ Time Frame: 32 months from treatment start ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

  • 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.

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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01244451

Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"
Ascoli, Italy
Unità Operativa Ematologia 1 - Università degli Studi di Bari
Bari, Italy, 70010
Ist.Ematologia e Oncologia Medica L.e A. Seragnoli
Bologna, Italy
Azienda Sanitaria di Bolzano - Ospedale Centrale - Ematologia e Centro TMO
Bolzano, Italy
Azienda ASL di Cagliari
Cagliari, Italy, 9121
U.O.C. di Onco-Ematologia - Centro di Ricerca e Formazione ad Alta tecnologia nelle Scienze Biomediche
Campobasso, Italy
Ospedale Ferrarotto
Catania, Italy, 95124
Azienda Ospedaliera Pugliese Ciaccio
Catanzaro, Italy, 88100
U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza
Cosenza, Italy
Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
Ferrara, Italy, 44100
Policlinico di Careggi, Università delgi studi di Firenze
Firenze, Italy
Clinica Ematologica - Università degli Studi
Genova, Italy
ASL Le1 P.O. Vito Fazzi - U.O. di Ematologia
Lecce, Italy, 73100
Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
Messina, Italy
Messina Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"
Messina, Italy
Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
Milano, Italy
Unità Trapianto di Midollo Ist. Nazionale Tumori
Milano, Italy
Sez. di medicina Interna Oncologia ed Ematologia
Modena, Italy
Ospedale San Gennaro - ASL Napoli 1
Napoli, Italy, 80143
U.O. Ematologia Clinica - Azienda USL di Pescara
Pescara, Italy
Dipartimento Emato-Oncologia A.O. "Bianchi-Melacrino-Morelli"
Reggio Calabria, Italy
S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
Roma, Italy
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
Roma, Italy
Università degli Studi - Policlinico di Tor Vergata
Roma, Italy
Università degli studi di Roma La Cattolica
Roma, Italy
Ospedale S.Eugenio
Rome, Italy, 00144
Ospedale Casa Sollievo della sofferenza
San Giovanni Rotondo, Italy
U.O. Ematologia, Azienda Ospedaliera Universitaria Senese
Siena, Italy, 53100
SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni
Terni, Italy
Div. di Ematologia "Molinette" Osp. Maggiore S. G. Battista
Torino, Italy
Clinica Ematologica - Policlinico Universitario
Udine, Italy
Policlinico G.B. Rossi
Verona, Italy, 37134
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Principal Investigator: Agostino Cortelezzi, Pr. Direzione Scientifica - Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

Additional Information:
Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto Identifier: NCT01244451     History of Changes
Other Study ID Numbers: CLL0809
First Posted: November 19, 2010    Key Record Dates
Last Update Posted: January 30, 2015
Last Verified: May 2014

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Additional relevant MeSH terms:
Bendamustine Hydrochloride
Antibodies, Monoclonal
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs