Trial of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Chronic Lymphocytic Leukemia
This study has been completed.
Information provided by (Responsible Party):
First received: June 18, 2012
Last updated: December 27, 2016
Last verified: December 2016
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).
Chronic Lymphocytic Leukemia
|Study Design:||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:
Genetic and Rare Diseases Information Center resources: Chronic Lymphocytic Leukemia Leukemia, B-cell, ChronicU.S. FDA Resources
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) ]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 ]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 ]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. ]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 ]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 ]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 ]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 ]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 ]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 ]To determine if IgVH mutation status relate to response to PCO therapy
|Study Start Date:||September 2011|
|Study Completion Date:||December 2016|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Subjects will receive up to 6 cycles of pentostatin, cyclophosphamide, and ofatumumab given every 21 days (+/- 4 days).
Lyophilized powder for intravenous administration.
Other Name: Nipent 10 mgDrug: Cyclophosphamide
Liquid concentrate for solution for infusion.
Other Name: Arzerra 100 mg
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.
Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01681563
Please refer to this study by its ClinicalTrials.gov identifier: NCT01681563
|Azienda Ospedaliera San Gerardo di Monza U.O. Ematologia|
|Monza, MB, Italy, 20052|
|IRCCS Istituto clinico Humanitas di Rozzano Dipartimento di Ematologia|
|Rozzano, Milano, Italy, 20089|
|Azienda Ospedaliera Ospedale Civile di Legnano U.O. Medicina Interna|
|Legnano, MI, Italy, 20025|
|A.O. Papa Giovanni XXIII U.S.C. Ematologia|
|Bergamo, Italy, 24128|
|Presidi Ospedalieri Spedali Civili di Brescia Divisione di Ematologia|
|Brescia, Italy, 25125|
|Ospedale Valduce S.C. Medicina Interna Sez. Ematologia|
|Como, Italy, 22100|
|Ospedale Maggiore Policlinico Università di Milano Istituto di Ematologia|
|Milano, Italy, 20122|
|IRCCS Fondazione Centro S. Raffaele del Monte Tabor Università Vita-Salute Dipartimento di Medicina Interna|
|Milano, Italy, 20132|
|Ospedale Cà Granda - Niguarda S.C: Ematologia|
|Milano, Italy, 20162|
|Azienda ospedaliera-universitaria Maggiore della Carità SCDU Ematologia|
|Novara, Italy, 28100|
|IRCCS Policlinico San Matteo Pavia Istituto di Ematologia|
|Pavia, Italy, 27100|
|A.O.U. Città della Salute e della Scienza Ospedale Molinette Divisione di Ematologia|
|Torino, Italy, 10126|
Sponsors and Collaborators
|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:||Giovanni Ucci, 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 Ospedale S. Raffaele 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:||Mauro Turrini, 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:||Marta Coscia, MD||AOU Città della Salute e della Scienza Ospedale Molinette 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|