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

NCT01681563

Last updated date
Study Location
Azienda Ospedaliera San Gerardo di Monza U.O. Ematologia
Monza, MB, 20052, Italy
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Chronic Lymphocytic Leukemia
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
65 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Diagnosis of B-CLL defined by:

1. 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

2. 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:

1. Unintentional Weight loss ³ 10% within the previous six months

2. Fevers > 38.0 °C for ≥ 2 weeks without evidence of infection

3. 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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:


1. Creatinine Clearance < 60 mL/min


2. Total bilirubin > 2.0 times upper normal limit (unless due to liver involvement
of BCLL)


3. 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

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Chronic Lymphocytic LeukemiaTrial of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Chronic Lymphocytic Leukemia
NCT01681563
  1. Monza, MB
  2. Rozzano, Milano
  3. Legnano, MI
  4. Bergamo,
  5. Brescia,
  6. Como,
  7. Milano,
  8. Milano,
  9. Milano,
  10. Novara,
  11. Pavia,
  12. Torino,
ALL GENDERS
65 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Trial of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Chronic Lymphocytic Leukemia
Official Title  ICMJE A Single-arm Multi-center Trial of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Previously Untreated Chronic Lymphocytic Leukemia
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).
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Pentostatin/Cyclophosphamide/Ofatumumab
Subjects will receive up to 6 cycles of pentostatin, cyclophosphamide, and ofatumumab given every 21 days (+/- 4 days).
Interventions:
  • Drug: Pentostatin
  • Drug: Cyclophosphamide
  • Drug: Ofatumumab
Publications * Tedeschi A, Rossi D, Motta M, Quaresmini G, Rossi M, Coscia M, Anastasia A, Rossini F, Cortelezzi A, Nador G, Scarfò 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 27, 2016)
47
Original Estimated Enrollment  ICMJE
 (submitted: September 5, 2012)
45
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of B-CLL defined by:

    1. 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
    2. 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:

    1. Unintentional Weight loss ³ 10% within the previous six months
    2. Fevers > 38.0 °C for ? 2 weeks without evidence of infection
    3. 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:

    1. Creatinine Clearance < 60 mL/min
    2. Total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of BCLL)
    3. 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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01681563
Other Study ID Numbers  ICMJE PCO
2010-022332-37 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Niguarda Hospital
Study Sponsor  ICMJE Niguarda Hospital
Collaborators  ICMJE
  • Regione Lombardia
  • GlaxoSmithKline
  • Hospira, now a wholly owned subsidiary of Pfizer
Investigators  ICMJE
Study Director:Marco Montillo, MDOspedale Cà Granda - Niguarda S.C: Ematologia
Principal Investigator:Agostino Cortelezzi, MDOspedale Maggiore Policlinico Università di Milano Istituto di Ematologia
Principal Investigator:Giovanni Ucci, MDASL della provincia di Lodi Presidio Ospedaliero di Lodi Dipartimento di Medicina Interna
Principal Investigator:Ester Orlandi, MDIRCCS Policlinico San Matteo Pavia Istituto di Ematologia
Principal Investigator:Fausto Rossini, MDAzienda Ospedaliera San Gerardo di Monza U.O. Ematologia
Principal Investigator:Armando Santoro, MDIRCCS Istituto Clinico Humanitas di Rozzano Dipartimento di Ematologia
Principal Investigator:Paolo Ghia, MDIRCCS Ospedale S. Raffaele Università Vita-Salute Dipartimento di Medicina Interna
Principal Investigator:Marina Motta, MDPresidi Ospedalieri Spedali Civili di Brescia Divisione di Ematologia
Principal Investigator:Gianluca Gaidano, MDAzienda Ospedaliero-Universitaria Maggiore della Carità - Struttura Complessa a Direzione Universitaria (SCDU Ematologia)
Principal Investigator:Mauro Turrini, MDOspedale Valduce S.C. Medicina Interna Sezione di Ematologia
Principal Investigator:Pierangelo Spedini, MDIstituti Ospitalieri di Cremona U.O.Complessa di Ematologia e CTMO
Principal Investigator:Marta Coscia, MDAOU Città della Salute e della Scienza Ospedale Molinette Divisione di Ematologia
Principal Investigator:Antonino Mazzone, MDAzienda Ospedaliera Ospedale Civile di Legnano U.O. Medicina Interna
Principal Investigator:Alessandro Rambaldi, MDA.O. Papa Giovanni XXIII di Bergamo USC Ematologia
PRS Account Niguarda Hospital
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP