GIMEMA CLL0809 Study (BendOfa)

NCT01244451 | Completed Phase 2 Results

• 1 other identifier: CLL0809
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 32

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  At 44 months from treatment start.

• Progression Free Survival

  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

  At 44 months from treatment start.

Study Arms (1)

Bendofa

EXPERIMENTAL

Bendamustine + Ofatumumab

Drug: Ofatumumab; Drug: Bendamustine

Interventions

Ofatumumab DRUG

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.

Bendofa

Bendamustine DRUG

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

Bendofa

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (32)

Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"

Ascoli Piceno, Italy

Location

Unità Operativa Ematologia 1 - Università degli Studi di Bari

Bari, 70010, Italy

Location

Ist.Ematologia e Oncologia Medica L.e A. Seragnoli

Bologna, Italy

Location

Azienda Sanitaria di Bolzano - Ospedale Centrale - Ematologia e Centro TMO

Bolzano, Italy

Location

Azienda ASL di Cagliari

Cagliari, 9121, Italy

Location

U.O.C. di Onco-Ematologia - Centro di Ricerca e Formazione ad Alta tecnologia nelle Scienze Biomediche

Campobasso, Italy

Location

Ospedale Ferrarotto

Catania, 95124, Italy

Location

Azienda Ospedaliera Pugliese Ciaccio

Catanzaro, 88100, Italy

Location

U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza

Cosenza, Italy

Location

Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna

Ferrara, 44100, Italy

Location

Policlinico di Careggi, Università delgi studi di Firenze

Florence, Italy

Location

Clinica Ematologica - Università degli Studi

Genova, Italy

Location

ASL Le1 P.O. Vito Fazzi - U.O. di Ematologia

Lecce, 73100, Italy

Location

Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina

Messina, Italy

Location

Messina Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"

Messina, Italy

Location

Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico

Milan, Italy

Location

Unità Trapianto di Midollo Ist. Nazionale Tumori

Milan, Italy

Location

Sez. di medicina Interna Oncologia ed Ematologia

Modena, Italy

Location

Ospedale San Gennaro - ASL Napoli 1

Napoli, 80143, Italy

Location

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, Italy

Location

Dipartimento Emato-Oncologia A.O. "Bianchi-Melacrino-Morelli"

Reggio Calabria, Italy

Location

S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena

Roma, Italy

Location

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

Roma, Italy

Location

Università degli Studi - Policlinico di Tor Vergata

Roma, Italy

Location

Università degli studi di Roma La Cattolica

Roma, Italy

Location

Ospedale S.Eugenio

Rome, 00144, Italy

Location

Ospedale Casa Sollievo della sofferenza

San Giovanni Rotondo, Italy

Location

U.O. Ematologia, Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni

Terni, Italy

Location

Div. di Ematologia "Molinette" Osp. Maggiore S. G. Battista

Torino, Italy

Location

Clinica Ematologica - Policlinico Universitario

Udine, Italy

Location

Policlinico G.B. Rossi

Verona, 37134, Italy

Location

Related Links

• GIMEMA Foundation Website

MeSH Terms

Conditions

Recurrence

Interventions

ofatumumab; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Alfonso Piciocchi
• Organization: GIMEMA

a.piciocchi@gimema.it

+39 06 70390528

Study Officials

• Agostino Cortelezzi, Pr.

  Direzione Scientifica - Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2010
• First Posted: November 19, 2010
• Study Start: December 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: January 25, 2019
• Results First Posted: January 25, 2019

Record last verified: 2019-01

Locations

IT (32)