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

NCT ID: NCT01681563

Last Updated: 2016-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2016-12-31

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pentostatin/Cyclophosphamide/Ofatumumab

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

Group Type: EXPERIMENTAL

Pentostatin

Intervention Type: DRUG

Lyophilized powder for intravenous administration.

Cyclophosphamide

Intervention Type: DRUG

IV

Ofatumumab

Intervention Type: DRUG

Liquid concentrate for solution for infusion.

Interventions

Pentostatin

Lyophilized powder for intravenous administration.

Intervention Type: DRUG

Cyclophosphamide

IV

Intervention Type: DRUG

Ofatumumab

Liquid concentrate for solution for infusion.

Intervention Type: DRUG

Other Intervention Names

Nipent 10 mg; Arzerra 100 mg

Eligibility Criteria

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

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regione Lombardia

OTHER

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Hospira, now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

Niguarda Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marco Montillo, MD

Role: STUDY_DIRECTOR

Ospedale Cà Granda - Niguarda S.C: Ematologia

Agostino Cortelezzi, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Maggiore Policlinico Università di Milano Istituto di Ematologia

Giovanni Ucci, MD

Role: PRINCIPAL_INVESTIGATOR

ASL della provincia di Lodi Presidio Ospedaliero di Lodi Dipartimento di Medicina Interna

Ester Orlandi, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Policlinico San Matteo Pavia Istituto di Ematologia

Fausto Rossini, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera San Gerardo di Monza U.O. Ematologia

Armando Santoro, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Istituto Clinico Humanitas di Rozzano Dipartimento di Ematologia

Paolo Ghia, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Ospedale S. Raffaele Università Vita-Salute Dipartimento di Medicina Interna

Marina Motta, MD

Role: PRINCIPAL_INVESTIGATOR

Presidi Ospedalieri Spedali Civili di Brescia Divisione di Ematologia

Gianluca Gaidano, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliero-Universitaria Maggiore della Carità - Struttura Complessa a Direzione Universitaria (SCDU Ematologia)

Mauro Turrini, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Valduce S.C. Medicina Interna Sezione di Ematologia

Pierangelo Spedini, MD

Role: PRINCIPAL_INVESTIGATOR

Istituti Ospitalieri di Cremona U.O.Complessa di Ematologia e CTMO

Marta Coscia, MD

Role: PRINCIPAL_INVESTIGATOR

AOU Città della Salute e della Scienza Ospedale Molinette Divisione di Ematologia

Antonino Mazzone, MD

Role: PRINCIPAL_INVESTIGATOR

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

Alessandro Rambaldi, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Papa Giovanni XXIII di Bergamo USC Ematologia

Locations

Azienda Ospedaliera San Gerardo di Monza U.O. Ematologia

Monza, MB, Italy

IRCCS Istituto clinico Humanitas di Rozzano Dipartimento di Ematologia

Rozzano, Milano, Italy

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

Legnano, MI, Italy

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

Bergamo, , Italy

Presidi Ospedalieri Spedali Civili di Brescia Divisione di Ematologia

Brescia, , Italy

Ospedale Valduce S.C. Medicina Interna Sez. Ematologia

Como, , Italy

Ospedale Maggiore Policlinico Università di Milano Istituto di Ematologia

Milan, , Italy

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

Milan, , Italy

Ospedale Cà Granda - Niguarda S.C: Ematologia

Milan, , Italy

Azienda ospedaliera-universitaria Maggiore della Carità SCDU Ematologia

Novara, , Italy

IRCCS Policlinico San Matteo Pavia Istituto di Ematologia

Pavia, , Italy

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

Torino, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 26294723 (View on PubMed)

Other Identifiers

2010-022332-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PCO

Identifier Type: -

Identifier Source: org_study_id