GIMEMA CLL0809 Study (BendOfa)
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.
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
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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|
- 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) ] [ Designated as safety issue: No ]
- 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) ] [ Designated as safety issue: No ]
- Toxicity according to CTCAE version 4.0 [ Time Frame: At 44 months from treatment start. ] [ Designated as safety issue: Yes ]
- 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. ] [ Designated as safety issue: No ]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.
- 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. ] [ Designated as safety issue: No ]Patients still alive and known to be progression free will be censored at the moment of last follow-up.
- 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. ] [ Designated as safety issue: No ]Patients still alive without receiving a new treatment will be censored at the time of the last follow-up.
- 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. ] [ Designated as safety issue: No ]Patients still alive will be censored at the moment of last follow-up.
- 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). ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Assess the relationship between ORR, PFS and CIRS total score at screening. [ Time Frame: 32 months from treatment start ] [ Designated as safety issue: No ]
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
|Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"|
|Unità Operativa Ematologia 1 - Università degli Studi di Bari|
|Bari, Italy, 70010|
|Ist.Ematologia e Oncologia Medica L.e A. Seragnoli|
|Azienda Sanitaria di Bolzano - Ospedale Centrale - Ematologia e Centro TMO|
|Azienda ASL di Cagliari|
|Cagliari, Italy, 9121|
|U.O.C. di Onco-Ematologia - Centro di Ricerca e Formazione ad Alta tecnologia nelle Scienze Biomediche|
|Catania, Italy, 95124|
|Azienda Ospedaliera Pugliese Ciaccio|
|Catanzaro, Italy, 88100|
|U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza|
|Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna|
|Ferrara, Italy, 44100|
|Policlinico di Careggi, Università delgi studi di Firenze|
|Clinica Ematologica - Università degli Studi|
|ASL Le1 P.O. Vito Fazzi - U.O. di Ematologia|
|Lecce, Italy, 73100|
|Messina Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"|
|Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina|
|Unità Trapianto di Midollo Ist. Nazionale Tumori|
|Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico|
|Sez. di medicina Interna Oncologia ed Ematologia|
|Ospedale San Gennaro - ASL Napoli 1|
|Napoli, Italy, 80143|
|U.O. Ematologia Clinica - Azienda USL di Pescara|
|Dipartimento Emato-Oncologia A.O. "Bianchi-Melacrino-Morelli"|
|Reggio Calabria, Italy|
|Università degli studi di Roma La Cattolica|
|S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena|
|Università degli Studi - Policlinico di Tor Vergata|
|Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia|
|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|
|Div. di Ematologia "Molinette" Osp. Maggiore S. G. Battista|
|Clinica Ematologica - Policlinico Universitario|
|Policlinico G.B. Rossi|
|Verona, Italy, 37134|
|Principal Investigator:||Agostino Cortelezzi, Pr.||Direzione Scientifica - Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena|