GIMEMA CLL0809 Study (BendOfa)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT01244451
First received: November 18, 2010
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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 Intervention 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
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

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 49
Study Start Date: December 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01244451

Locations
Italy
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
Messina Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"
Messina, Italy
Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
Messina, Italy
Unità Trapianto di Midollo Ist. Nazionale Tumori
Milano, Italy
Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
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
Università degli studi di Roma La Cattolica
Roma, Italy
S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
Roma, Italy
Università degli Studi - Policlinico di Tor Vergata
Roma, Italy
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
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
Investigators
Principal Investigator: Agostino Cortelezzi, Pr. Direzione Scientifica - Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
  More Information

Additional Information:
No publications provided

Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT01244451     History of Changes
Other Study ID Numbers: CLL0809
Study First Received: November 18, 2010
Last Updated: May 12, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
CLL
relapsed
refractory
Bendamustine
Ofatumumab

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014