Trial of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Chronic Lymphocytic Leukemia
This study is currently recruiting participants.
Verified May 2013 by Niguarda Hospital
Sponsor:
Niguarda Hospital
Collaborators:
Regione Lombardia
GlaxoSmithKline
Hospira, Inc.
Information provided by (Responsible Party):
Niguarda Hospital
ClinicalTrials.gov Identifier:
NCT01681563
First received: June 18, 2012
Last updated: May 6, 2013
Last verified: May 2013
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Purpose
This is a phase II multicenter, non-comparative, open label study in older previously untreated Chronic Lymphocytic Leukaemia patients, requiring therapy, aimed at defining the efficacy profile (ORR, CRR and TTP) of pentostatin and cyclophosphamide given in combination with Ofatumumab (PCO).
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Lymphocytic Leukemia |
Drug: Pentostatin Drug: Cyclophosphamide Drug: Ofatumumab |
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 Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Previously Untreated Chronic Lymphocytic Leukemia |
Resource links provided by NLM:
Further study details as provided by Niguarda Hospital:
Primary Outcome Measures:
- Overall Response Rate (ORR) [ Time Frame: 2 months after the last dose received (End of treatment period) ] [ Designated as safety issue: No ]To assess the overall response rate (ORR) using pentostatin, cyclophosphamide, and ofatumumab in patients with previously untreated CLL requiring therapy.
Secondary Outcome Measures:
- Adverse Events according to CTCAE, Version 3.0 NCI CTCAE [ Time Frame: From informed consent signed through to 28 days after the last study drug administration ] [ Designated as safety issue: No ]To monitor and assess toxicity of pentostatin, cyclophosphamide, and ofatumumab in patients with previously untreated CLL.
- Complete Response Rate (CRR) [ Time Frame: Baseline, at cycle 3 and 2 months after the last dose received ] [ Designated as safety issue: No ]To assess the complete response of CLL patients treated with pentostatin, cyclophosphamide, and ofatumumab
- Minimal Residual Disease (MRD) [ Time Frame: Every 3 months from the last dose of treatment up to 2 years follow up. ] [ Designated as safety issue: No ]To determine the proportion of patients who achieve a minimal residual disease (MRD) negative state as assessed by flow cytometry.It will be assessed only in patients responding to PCO treatment.
- Progression-Free Survival [ Time Frame: Measured as the time from inclusion in the trial to disease progression or death, assessed up to 2 years ] [ Designated as safety issue: No ]To determine the progression-free survival in CLL patients treated with pentostatin,cyclophosphamide, and ofatumumab.
- Overall Survival (OS) [ Time Frame: Measured as the time from inclusion in the trial until death from any cause, assessed up to 2 years of follow up ] [ Designated as safety issue: No ]To assess overall survival (OS) of CLL patients treated with pentostatin, cyclophosphamide, and ofatumumab
- Time To Progression (TTP) [ Time Frame: Measured as the time from inclusion in the trial until disease progression or death, assessed up to 2 years ] [ Designated as safety issue: No ]To assess the time-to-progression (TTP) of CLL patients treated with pentostatin, cyclophosphamide, and ofatumumab
- Genetic analysis by Fish [ Time Frame: Baseline, 2 months after the last dose received and at month 12 and 24 during follow up ] [ Designated as safety issue: No ]To determine if cytogenetic abnormalities identified by FISH, relate to response to PCO therapy.
- Ofatumumab pharmacokinetics parameter [ Time Frame: Cycle1: Day 1, 2, 3, 8, 9, 15. Cycles 2-5: Day 1, 2, 3, 8,15. Cycle 6: Day 1, 2, 3, 8, 15, 21 ] [ Designated as safety issue: No ]To assess ofatumumab pharmacokinetic parameters
- IgVH mutation status [ Time Frame: Baseline, 2 months after the last dose received and at month 12 and 24 during follow up ] [ Designated as safety issue: No ]To determine if IgVH mutation status relate to response to PCO therapy
| Estimated Enrollment: | 45 |
| Study Start Date: | September 2011 |
| Estimated Study Completion Date: | November 2015 |
| Estimated Primary Completion Date: | July 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Pentostatin/Cyclophosphamide/Ofatumumab
Subjects will receive up to 6 cycles of pentostatin, cyclophosphamide, and ofatumumab given every 21 days (+/- 4 days).
|
Drug: Pentostatin
Lyophilized powder for intravenous administration.
Other Name: Nipent 10 mg
Drug: Cyclophosphamide
IV
Drug: Ofatumumab
Liquid concentrate for solution for infusion.
Other Name: Arzerra 100 mg
|
Detailed Description:
Chronic lymphocytic leukemia (CLL) is the most common of the chronic lymphoid leukemias, comprising 30% of all adult leukemias. The majority of CLL patients are of advanced age. Currently, immunochemotherapy with Rituximab, Fludarabine and Cyclophosphamide (RFC) is the standard of care in previously untreated patients with CLL requiring treatment. The combination of Pentostatin and Cyclophosphamide has generated excellent clinical response rates in pretreated B-CLL patients. Early data on the use of Ofatumumab as a single agent in Fludarabine-refractory CLL patients have been reported. Given the reported efficacy of chemo-immunotherapy combinations in CLL and the promising activity and toxicity profile of Pentostatin combinations, we designed a trial of Pentostatin, Cyclophosphamide, and Ofatumumab for previously untreated older patients with CLL. The aim is improving efficacy, in Rituximab resistant CLL, and toxicity considering the good profile of tolerability showed using Ofatumumab as single agent.
Eligibility| Ages Eligible for Study: | 65 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
Diagnosis of B-CLL defined by:
- Circulating lymphocytes of more than or equal to 5 x109/L B lymphocytes (5000/mL) in the peripheral blood for the duration of at least 3 months. AND
- Flow cytometry confirmation of immunophenotype: CD5, CD19, CD20, CD23, CD79b, and surface Ig
- Age ≥ 65 years
- Active disease and indication for treatment based on modified NCI-WG guidelines defined by presenting at least any one of the following conditions:
- Evidence of progressive marrow failure as manifested by development of, or worsening of anemia and/or thrombocytopenia
- Massive (i.e. > 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
- Massive nodes (i.e. > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
- Progressive lymphocytosis with an increase of > 50% over a two month period or an lymphocyte doubling time < 6 months
A minimum of any one of the following disease-related symptoms must be present:
- Unintentional Weight loss ³ 10% within the previous six months
- Fevers > 38.0 °C for ≥ 2 weeks without evidence of infection
- Night sweats for more than 1 month without evidence of infection
- Not been previously treated for B-CLL (prior autoimmune hemolytic anemia treatment permitted)
- ECOG Performance Status of 0-2
- Signed written informed consent prior to performing any study-specific procedures
Exclusion Criteria:
- Prior therapy for B-CLL with any agent except corticosteroids used to treat autoimmune hemolytic anemia
- Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy > 100 mg equivalent to hydrocortisone, or chemotherapy
- Known Richter transformation
- Known CNS involvement of B-CLL
- Any radiation therapy ≤ 4 weeks prior to registration;
- Any major surgery ≤ 4 weeks prior to registration;
- Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C
- Past or current malignancy with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or the breast unless the tumor was successfully treated with curative intend at least 2 years prior to trial entry.
- Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
- History of significant cerebrovascular disease
- Glucocorticoid unless given in doses ≤ 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoid) if for exacerbations other than B-CLL (e.g. asthma)
- Known HIV positive
- Positive serology for Hepatitis B (HB), defined as a positive test for HBsAg. In addition if negative for HBsAg but HBcAb positive and HBsAb negative a HB DNA test will be performed and if positive the subject will be excluded. Note: if HBcAb positive and HBsAb positive, which is indicative of a past infection, the subject can be included.
Screening laboratory values:
- Creatinine Clearance < 60 mL/min
- Total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of BCLL)
- ALT > 3.0 times upper normal limit (unless due to liver involvement of B-CLL)
- Treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 1 or currently participating in any other interventional clinical study
- Known or suspected inability to comply with the study protocol
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01681563
Contacts
| Contact: Marco Montillo, MD | +39 02 64444074/2668 | marco.montillo@ospedaleniguarda.it |
Locations
| Italy | |
| Azienda Ospedaliera San Gerardo di Monza U.O. Ematologia | Recruiting |
| Monza, MB, Italy, 20052 | |
| Contact: Fausto Rossini, MD +39 0392339078 f.rossini@hsgerardo.org | |
| Principal Investigator: Fausto Rossini, MD | |
| IRCCS Istituto clinico Humanitas di Rozzano Dipartimento di Ematologia | Recruiting |
| Rozzano, Milano, Italy, 20089 | |
| Contact: Armando Santoro, MD armando.santoro@humanitas.it | |
| Principal Investigator: Antonella Anastasia, MD | |
| Azienda Ospedaliera Ospedale Civile di Legnano U.O. Medicina Interna | Recruiting |
| Legnano, MI, Italy, 20025 | |
| Contact: Antonino Mazzone, MD +390331449211 antonino.mazzone@ao-legnano.it | |
| Principal Investigator: Antonino Mazzone, MD | |
| Ospedale dell' Angelo | Recruiting |
| Venezia Mestre, VE, Italy, 30174 | |
| Contact: Renato Bassan, MD +39 041 9657362 Renato.Bassan@ulss12.ve.it | |
| Principal Investigator: Renato Bassan, MD | |
| A.O. Papa Giovanni XXIII U.S.C. Ematologia | Recruiting |
| Bergamo, Italy, 24128 | |
| Contact: Alessandro Rambaldi, MD +39035266808 arambaldi@hpg23.it | |
| Principal Investigator: Alessandro Rambaldi, MD | |
| Presidi Ospedalieri Spedali Civili di Brescia Divisione di Ematologia | Recruiting |
| Brescia, Italy, 25125 | |
| Contact: Marina Motta, MD +390303996573 marina.motta@spedalicivili.brescia.it | |
| Principal Investigator: Marina Motta, MD | |
| Ospedale Valduce S.C. Medicina Interna Sez. Ematologia | Recruiting |
| Como, Italy, 22100 | |
| Contact: Roberto Cairoli, MD +39031324111 rcairoli@valduce.it | |
| Principal Investigator: Roberto Cairoli, MD | |
| Istituti Ospitalieri di Cremona U.O.C. Ematologia e Centro Trapianti Midollo Osseo | Recruiting |
| Cremona, Italy, 26100 | |
| Contact: Pierangelo Spedini, MD +390372405669 pierangelo.spedini@virgilio.it | |
| Principal Investigator: Pierangelo Spedini, MD | |
| ASL della Provincia di Lodi Presidio Ospedaliero di Lodi Dipartimento di Medicina Interna | Recruiting |
| Lodi, Italy, 26900 | |
| Contact: Giulio Nalli, MD +39 0371 372220 giulio.nalli@ao.lodi.it | |
| Principal Investigator: Giulio Nalli, MD | |
| IRCCS Fondazione Centro S. Raffaele del Monte Tabor Università Vita-Salute Dipartimento di Medicina Interna | Recruiting |
| Milano, Italy, 20132 | |
| Contact: Paolo Ghia, MD +390226434797 ghia.paolo@hsr.it | |
| Principal Investigator: Paolo Ghia, MD | |
| Ospedale Cà Granda - Niguarda S.C: Ematologia | Recruiting |
| Milano, Italy, 20162 | |
| Contact: Marco Montillo, MD +39 02 64444074/2668 marco.montillo@ospedaleniguarda.it | |
| Principal Investigator: Marco Montillo, MD | |
| Ospedale Maggiore Policlinico Università di Milano Istituto di Ematologia | Recruiting |
| Milano, Italy, 20122 | |
| Contact: Agostino Cortelezzi, MD +39 02 5503.3322 agostino.cortelezzi@unimi.it | |
| Principal Investigator: Agostino Cortelezzi, MD | |
| Azienda ospedaliera-universitaria Maggiore della Carità SCDU Ematologia | Recruiting |
| Novara, Italy, 28100 | |
| Contact: Gianluca Gaidano, MD +390321660655 gianluca.gaidano@med.unipmn.it | |
| Principal Investigator: Gianluca Gaidano, MD | |
| IRCCS Policlinico San Matteo Pavia Istituto di Ematologia | Recruiting |
| Pavia, Italy, 27100 | |
| Contact: Ester Orlandi, MD +39 0382503596 eorlandi@smatteo.pv.it | |
| Principal Investigator: Ester Orlandi, MD | |
| A.O.U. Le Molinette San Giovanni Battista Divisione di Ematologia | Recruiting |
| Torino, Italy, 10126 | |
| Contact: Massimo Massaia, MD massimo.massaia@unito.it | |
| Principal Investigator: Massimo Massaia, MD | |
Sponsors and Collaborators
Niguarda Hospital
Regione Lombardia
GlaxoSmithKline
Hospira, Inc.
Investigators
| Study Director: | Marco Montillo, MD | Ospedale Cà Granda - Niguarda S.C: Ematologia |
| Principal Investigator: | Agostino Cortelezzi, MD | Ospedale Maggiore Policlinico Università di Milano Istituto di Ematologia |
| Principal Investigator: | Giulio Nalli, MD | ASL della provincia di Lodi Presidio Ospedaliero di Lodi Dipartimento di Medicina Interna |
| Principal Investigator: | Ester Orlandi, MD | IRCCS Policlinico San Matteo Pavia Istituto di Ematologia |
| Principal Investigator: | Fausto Rossini, MD | Azienda Ospedaliera San Gerardo di Monza U.O. Ematologia |
| Principal Investigator: | Armando Santoro, MD | IRCCS Istituto Clinico Humanitas di Rozzano Dipartimento di Ematologia |
| Principal Investigator: | Paolo Ghia, MD | IRCCS Fondazione Centro S. Raffaele del Monte Tabor Università Vita-Salute Dipartimento di Medicina Interna |
| Principal Investigator: | Marina Motta, MD | Presidi Ospedalieri Spedali Civili di Brescia Divisione di Ematologia |
| Principal Investigator: | Gianluca Gaidano, MD | Azienda Ospedaliero-Universitaria Maggiore della Carità - Struttura Complessa a Direzione Universitaria (SCDU Ematologia) |
| Principal Investigator: | Roberto Cairoli, MD | Ospedale Valduce S.C. Medicina Interna Sezione di Ematologia |
| Principal Investigator: | Pierangelo Spedini, MD | Istituti Ospitalieri di Cremona U.O.Complessa di Ematologia e CTMO |
| Principal Investigator: | Massimo Massaia, MD | AOU Le Molinette San Giovanni Battista Divisione di Ematologia |
| Principal Investigator: | Antonino Mazzone, MD | Azienda Ospedaliera Ospedale Civile di Legnano U.O. Medicina Interna |
| Principal Investigator: | Alessandro Rambaldi, MD | A.O. Papa Giovanni XXIII di Bergamo USC Ematologia |
| Principal Investigator: | Renato Bassan, MD | Ospedale dell' Angelo Venezia Mestre |
More Information
No publications provided
| Responsible Party: | Niguarda Hospital |
| ClinicalTrials.gov Identifier: | NCT01681563 History of Changes |
| Other Study ID Numbers: | PCO, 2010-022332-37 |
| Study First Received: | June 18, 2012 |
| Last Updated: | May 6, 2013 |
| Health Authority: | Italy: The Italian Medicines Agency Italy: Coordinating center administration |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cyclophosphamide Pentostatin Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Adenosine Deaminase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 21, 2013