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Chronic Lymphocytic LeukemiaPhase 2NCT01681563

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

A Phase 2 study testing Pentostatin, Cyclophosphamide and Ofatumumab in people with Chronic Lymphocytic Leukemia, run by Niguarda Hospital at 12 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 65 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Pentostatin, Cyclophosphamide and Ofatumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
12 sitesItaly
Study dates
Sep 2011to Dec 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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;
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  • 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

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Italy12 sites

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

    Bergamo, 24128

  • Presidi Ospedalieri Spedali Civili di Brescia Divisione di Ematologia

    Brescia, 25125

  • Ospedale Valduce S.C. Medicina Interna Sez. Ematologia

    Como, 22100

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

    Legnano, MI, 20025

  • Ospedale Maggiore Policlinico Università di Milano Istituto di Ematologia

    Milan, 20122

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

    Milan, 20132

  • Ospedale Cà Granda - Niguarda S.C: Ematologia

    Milan, 20162

  • Azienda Ospedaliera San Gerardo di Monza U.O. Ematologia

    Monza, MB, 20052

  • Azienda ospedaliera-universitaria Maggiore della Carità SCDU Ematologia

    Novara, 28100

  • IRCCS Policlinico San Matteo Pavia Istituto di Ematologia

    Pavia, 27100

  • IRCCS Istituto clinico Humanitas di Rozzano Dipartimento di Ematologia

    Rozzano, Milano, 20089

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

    Torino, 10126

Other trials in Italy

About this study

Official title: A Single-arm Multi-center Trial of Pentostatin Plus Cyclophosphamide With Ofatumumab (PCO) in Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

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).

Read the 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.

Being tested
Pentostatin, Cyclophosphamide, Ofatumumab
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PentostatinDrug

    Also called Nipent 10 mg

    Lyophilized powder for intravenous administration.

  • CyclophosphamideDrug

    IV

  • OfatumumabDrug

    Also called Arzerra 100 mg

    Liquid concentrate for solution for infusion.

Study groups in NCT01681563
Study groupRoleWhat they receive
Pentostatin/Cyclophosphamide/OfatumumabExperimentalSubjects will receive up to 6 cycles of pentostatin, cyclophosphamide, and ofatumumab given every 21 days (+/- 4 days).
Receives: Drug: Pentostatin; Drug: Cyclophosphamide; Drug: Ofatumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)

  1. Adverse Events according to CTCAE, Version 3.0 NCI CTCAE

    To monitor and assess toxicity of pentostatin, cyclophosphamide, and ofatumumab in patients with previously untreated CLL.

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

  2. Complete Response Rate (CRR)

    To assess the complete response of CLL patients treated with pentostatin, cyclophosphamide, and ofatumumab

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

  3. Minimal Residual Disease (MRD)

    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.

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

  4. Progression-Free Survival

    To determine the progression-free survival in CLL patients treated with pentostatin,cyclophosphamide, and ofatumumab.

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

  5. Overall Survival (OS)

    To assess overall survival (OS) of CLL patients treated with pentostatin, cyclophosphamide, and ofatumumab

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

  6. Time To Progression (TTP)

    To assess the time-to-progression (TTP) of CLL patients treated with pentostatin, cyclophosphamide, and ofatumumab

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

  7. Genetic analysis by Fish

    To determine if cytogenetic abnormalities identified by FISH, relate to response to PCO therapy.

    Measured: Baseline, 2 months after the last dose received and at month 12 and 24 during follow up

  8. Ofatumumab pharmacokinetics parameter

    To assess ofatumumab pharmacokinetic parameters

    Measured: 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

  9. IgVH mutation status

    To determine if IgVH mutation status relate to response to PCO therapy

    Measured: Baseline, 2 months after the last dose received and at month 12 and 24 during follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2012 (estimated)
  2. Study startSep 2011
  3. Primary completionNov 2015
  4. Study completionDec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01681563
Sponsor's protocol ID
PCO
Other IDs
2010-022332-37
Status last verified
Dec 2016
First submitted
18 Jun 2012
Last updated
28 Dec 2016
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 26294723

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pentostatin, Cyclophosphamide and Ofatumumab in people with Chronic Lymphocytic Leukemia, run by Niguarda Hospital at 12 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: 2 months after the last dose received (End of treatment period)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01681563, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2016.

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