Trial of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Chronic Lymphocytic Leukemia

NCT01681563 | Completed Phase 2

• 2 other identifiers: PCO2010-022332-37
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 12

Brief Summary

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).

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  To assess the overall response rate (ORR) using pentostatin, cyclophosphamide, and ofatumumab in patients with previously untreated CLL requiring therapy.

  2 months after the last dose received (End of treatment period)

Secondary Outcomes (9)

• Adverse Events according to CTCAE, Version 3.0 NCI CTCAE

  From informed consent signed through to 28 days after the last study drug administration

• Complete Response Rate (CRR)

  Baseline, at cycle 3 and 2 months after the last dose received

• Minimal Residual Disease (MRD)

  Every 3 months from the last dose of treatment up to 2 years follow up.

• Progression-Free Survival

  Measured as the time from inclusion in the trial to disease progression or death, assessed up to 2 years

• Overall Survival (OS)

  Measured as the time from inclusion in the trial until death from any cause, assessed up to 2 years of follow up

Study Arms (1)

Pentostatin/Cyclophosphamide/Ofatumumab

EXPERIMENTAL

Subjects will receive up to 6 cycles of pentostatin, cyclophosphamide, and ofatumumab given every 21 days (+/- 4 days).

Drug: Pentostatin; Drug: Cyclophosphamide; Drug: Ofatumumab

Interventions

Pentostatin DRUG

Lyophilized powder for intravenous administration.

Also known as: Nipent 10 mg

Pentostatin/Cyclophosphamide/Ofatumumab

Cyclophosphamide DRUG

IV

Pentostatin/Cyclophosphamide/Ofatumumab

Ofatumumab DRUG

Liquid concentrate for solution for infusion.

Also known as: Arzerra 100 mg

Pentostatin/Cyclophosphamide/Ofatumumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Niguarda Hospital: lead
• Regione Lombardia: collaborator
• GlaxoSmithKline: collaborator
• Hospira, now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (12)

Azienda Ospedaliera San Gerardo di Monza U.O. Ematologia

Monza, MB, 20052, Italy

Location

IRCCS Istituto clinico Humanitas di Rozzano Dipartimento di Ematologia

Rozzano, Milano, 20089, Italy

Location

Azienda Ospedaliera Ospedale Civile di Legnano U.O. Medicina Interna

Legnano, MI, 20025, Italy

Location

A.O. Papa Giovanni XXIII U.S.C. Ematologia

Bergamo, 24128, Italy

Location

Presidi Ospedalieri Spedali Civili di Brescia Divisione di Ematologia

Brescia, 25125, Italy

Location

Ospedale Valduce S.C. Medicina Interna Sez. Ematologia

Como, 22100, Italy

Location

Ospedale Maggiore Policlinico Università di Milano Istituto di Ematologia

Milan, 20122, Italy

Location

IRCCS Fondazione Centro S. Raffaele del Monte Tabor Università Vita-Salute Dipartimento di Medicina Interna

Milan, 20132, Italy

Location

Ospedale Cà Granda - Niguarda S.C: Ematologia

Milan, 20162, Italy

Location

Azienda ospedaliera-universitaria Maggiore della Carità SCDU Ematologia

Novara, 28100, Italy

Location

IRCCS Policlinico San Matteo Pavia Istituto di Ematologia

Pavia, 27100, Italy

Location

A.O.U. Città della Salute e della Scienza Ospedale Molinette Divisione di Ematologia

Torino, 10126, Italy

Location

Related Publications (1)

• Tedeschi A, Rossi D, Motta M, Quaresmini G, Rossi M, Coscia M, Anastasia A, Rossini F, Cortelezzi A, Nador G, Scarfo L, Cairoli R, Frustaci AM, Dalceggio D, Picardi P, De Paoli L, Orlandi E, Rambaldi A, Massaia M, Gaidano G, Montillo M; Rete Ematologica Lombarda-CLL Workgroup. A phase II multi-center trial of pentostatin plus cyclophosphamide with ofatumumab in older previously untreated chronic lymphocytic leukemia patients. Haematologica. 2015 Dec;100(12):e501-4. doi: 10.3324/haematol.2015.132035. Epub 2015 Aug 20. No abstract available.

  PMID: 26294723 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Pentostatin; Cyclophosphamide; ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Marco Montillo, MD

  Ospedale Cà Granda - Niguarda S.C: Ematologia

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

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: June 18, 2012
• First Posted: September 10, 2012
• Study Start: September 1, 2011
• Primary Completion: November 1, 2015
• Study Completion: December 1, 2016
• Last Updated: December 28, 2016

Record last verified: 2016-12

Locations

IT (12)