Clinical trial NCT01321541: Comparison of Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma or Follicular Grade 3 Lymphoma Who Have Relapsed After Therapy and Are Not Eligible for Stem Cell Transplant
Official title: A Randomized Multicenter Study Comparing Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma Who Have Relapsed After Therapy With CHOP-R or an Equivalent Regimen and Are Ineligible for Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diffuse Large B-cell Lymphoma
de Novo DLBCL
DLBCL Transformed From Indolent Lymphoma
Follicular Grade 3 Lymphoma
Keywords: non-hodgkin lymphoma
DLBCL
relapsed
aggressive NHL
Diffuse large B-cell lymphoma
Rituximab
Rituxan
Pixantrone
NHL
non hodgkin's lymphoma
de novo DLBCL
DLBCL transformed from Indolent Lymphoma
Follicular Grade 3 Lymphoma
Lead sponsor: CTI BioPharma
Sponsor class: INDUSTRY
First posted: 2011-03-23
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of Pixantrone + Rituximab compared to Gemcitabine + Rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), or follicular grade 3 lymphoma.

Detailed description: Eligible patients will be randomized to treatment with pixantrone plus rituximab or gemcitabine plus rituximab in up to six 28-day cycles. At the time patients experience progressive disease during study treatment, early follow- up, or intermediate follow-up, they enter the survival follow up period. Patients who complete study treatment or discontinue study treatment for any other reason will participate in the follow-up periods.

Early Follow-Up: After treatment completion or discontinuation, patient will enter a 24-week follow-up period.

Intermediate Follow-Up: After completing the 24-week early follow-up period, patient will enter an additional 72-week follow-up period.

Survival Follow-Up: All patients will be monitored for survival.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of DLBCL (de novo DLBCL, or transformed from indolent lymphoma) or follicular grade 3 lymphoma on the basis of tissue biopsy.
2. Patients with de novo DLBCL must have received 1-3 treatment regimens for DLBCL. Patients with follicular grade 3 lymphoma must have received 1-3 treatment regimens for follicular lymphoma (any grade). Patients with DLBCL transformed from indolent lymphoma must have received at least 1-4 treatment regimens for NHL.
3. Received rituximab containing a multi-agent therapy for the treatment of NHL.
4. Not eligible for high-dose chemotherapy and stem cell transplant.
5. Patients with DLBCL transformed from indolent lymphoma must have had a complete or partial response to a therapy for NHL lasting at least 12 weeks.

Exclusion Criteria:

1. Primary refractory de novo DLBCL or primary refractory follicular grade 3 lymphoma, defined as documented progression within 12 weeks of the last cycle of the first-line multi-agent regimen.
2. Prior treatment with cumulative dose of doxorubicin or equivalent exceeding 450 mg/m2
3. Any experimental therapy ≤ 28 days prior to randomization
4. Other malignancy within last 5 years except for the following: curatively treated basal cell/squamous cell skin cancer, carcinoma in situ of the cervix, superficial transitional cell bladder carcinoma, or in situ ductal carcinoma of the breast after complete resection
5. Any contraindication or known allergy or hypersensitivity to any study drugs
6. Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies. Low-dose corticosteroids for the treatment of non cancer-related illnesses are permitted.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From the date of randomization to the date of progressive disease or death due to any cause (whichever is first reported) (Up to 100 weeks)
Secondary outcomes:
measure: Overall Survival
timeFrame: From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)
measure: Complete Response Rate
timeFrame: From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)
measure: Overall Response Rate
timeFrame: From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)
measure: Number of Treatment Emergent Adverse Events (TEAE) Related to Study Drug
timeFrame: From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)
Other outcomes:
measure: Individual Concentration-time Profiles of Patients Will be Compared to Existing Data Using Simulations (Visual Predictive Checks)
timeFrame: within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion
measure: To Generate Individual Secondary PK Parameters (eg, Exposure, Half-life Etc.) Using Descriptive Statistics
timeFrame: within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Bentonville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Washington
country: United States
facility: George Washington University Department of Medicine
state: District of Columbia
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network-St. Vincent's
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network-Southside
state: Florida
city: Orange Park
country: United States
facility: Integrated Community Oncology Network
state: Florida
city: Danville
country: United States
facility: Carle Physician Group
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Central Illinois
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Mattoon
country: United States
facility: Carle Foundation Physician Services
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Louisville
country: United States
facility: Baptist Hospital East
state: Kentucky
city: Baltimore
country: United States
facility: Harry and Jeanette Weinberg Cancer Institute at Franklin Square
state: Maryland
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders, PC
state: Maryland
city: Grand Rapids
country: United States
facility: Cancer & Hematology Center of Western Michigan
state: Michigan
city: Fridley
country: United States
facility: Metro Minnesota CCOP-Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Metro Minnesota CCOP-St. Johns
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro Minnesota Community Clinical Oncology Program
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro Minnesota Community Clinical Oncology Program
state: Minnesota
city: Saint Paul
country: United States
facility: Metro Minnesota CCOP-Regions Hospital
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Hematology-Oncology, PC
state: Nebraska
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern New Jersey
state: New Jersey
city: East Setauket
country: United States
facility: North Shore Hematology/Oncology Associates
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Dover
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinical Cancer Center
state: Ohio
city: Toledo
country: United States
facility: Mercy Cancer Center at St. Anne's
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center-Toledo
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists, PC
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, PC
state: Oregon
city: Tualatin
country: United States
facility: Northwest Cancer Specialists, PC
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Upstate Oncology Associates
state: South Carolina
city: Hardeeville
country: United States
facility: South Carolina Cancer Specialists
state: South Carolina
city: Hilton Head Island
country: United States
facility: South Carolina Cancer Specialists
state: South Carolina
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: New Braunfels
country: United States
facility: Cancer Care Centers of South Texas-HOAST
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas-HOAST
state: Texas
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, PC
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, PC
state: Washington
city: Green Bay
country: United States
facility: Saint Vincent Hospital Green Bay Oncology
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology-St. Mary's Hospital MC
state: Wisconsin
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology)
city: Linz
country: Austria
facility: Hospital Elisabethinen Linz, Internal Department 1 - Hemato-Oncology
city: Vienna
country: Austria
facility: Hanusch Hospital, Department of Internal Medicine III
city: Brussels
country: Belgium
facility: Saint Luc University Hospital, Department of Hematology
city: Roeselare
country: Belgium
facility: General Hospital Delta, Hematology Department
city: Turnhout
country: Belgium
facility: General Hospital Turnhout, Hematology Department
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sveti Georgi", Plovdiv, Clinical Hematology Clinic
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sveti Georgi", Plovdiv, Department of Medical Oncology
city: Sofia
country: Bulgaria
facility: MHAT "Tokuda Hospital Sofia", Hematology Clinic
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Department of Clinical Hematology
city: Sofia
country: Bulgaria
facility: Specialized Hospital For Active Treatment Of Hematological Diseases, Sofia, Clinical Hematology Clinic
city: Vratsa
country: Bulgaria
facility: MHAT Hristo Botev, Vratsa, First Department of Internal Medicine
city: Brno
country: Czechia
facility: University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
city: Hradec Kralove
country: Czechia
facility: University Hospital Hradec Kralove, 4th Department of Internal Medicne, Clinical Hematology
city: Ostrava
country: Czechia
facility: University Hospital Ostrava, Institute of Clinical Hematology
city: Prague
country: Czechia
facility: University Hospital Kralovske Vinohrady, Department of Clinical Hematology
city: Prague
country: Czechia
facility: General University Hospital in Prague, 1st Department of Internal Medicine - Department of Hematology
city: Aalborg
country: Denmark
facility: Aalborg University Hospital, Department of Hematology
city: Amiens, Cedex 1
country: France
facility: Service d'hématologie clinique, Avenue Laennec Salouel
city: Bayonne
country: France
facility: Centre hopitalier de la cote basque
city: Beziers
country: France
facility: Centre hospitalier de Beziers
city: Bordeaux
country: France
facility: Polyclinique de Bordeaux nord Acquitaine
city: Le Mans Cedex 03
country: France
facility: Centre hospitalier du Mans
city: Pierre Benite Cedex
country: France
facility: Centre hospitalier Lyon Sud
city: Saint-Quentin
country: France
facility: Saint Quentin Hospital Center, Department of Oncology-Hematology
city: Strasbourg Cedex
country: France
facility: Hautepierre Hospital, Department of Hematology and Oncology
city: Aschaffenburg
country: Germany
facility: Gemeinschaftspraxis Drs. Klausmann
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Frankfurt (a.M.)
country: Germany
facility: Klinik für Innere Medizin III
city: Halle (Saale)
country: Germany
facility: Universitaetsklinikum Halle
city: Hamm
country: Germany
facility: St. Marien Hospital Hamm
city: Köln
country: Germany
facility: Universitätsklinik Köln
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromäerinnen
city: Budapest
country: Hungary
facility: St. Istvan and St. Laszlo Hospital of Budapest
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Kaposvár
country: Hungary
facility: Moritz Kaposi General Hospital
city: Ancona
country: Italy
facility: University Hospital "Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi"
city: Bologna
country: Italy
facility: Bologna University Hospital Authority St. Orsola-Malpighi Polyclinic
city: Meldola
country: Italy
facility: Scientific Institute of Romagna for the Study and Treatment of Cancer (I.R.S.T.) S.R.L.
city: Palermo
country: Italy
facility: "Ospedali Riuniti Villa Sofia-Cervello" Hospital
city: Ravenna
country: Italy
facility: Romagna Local Health Authority (AUSL Romagna) - "Santa Maria delle Croci"
city: Rimini
country: Italy
facility: Romagna Local Health Authority (AUSL Romagna) - "Infermi" Hospital
city: Siena
country: Italy
facility: Siena University Hospital Authority Santa Maria alle Scotte Polyclinic
city: Terni
country: Italy
facility: Santa Maria Hospital
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino
city: Chorzów
country: Poland
facility: Independent Public Healthcare Facility Municipal Hospital Group
city: Gdynia
country: Poland
facility: Marine Hospital of Polish Red Cross, Department of Chemotheraphy
city: Katowice
country: Poland
facility: Silesia Medical University, Department of Hematology and Bone Marrow Transplantation
city: Krakow
country: Poland
facility: Malopolskie Medical Center S.C. , Department of Hematology
city: Lodz
country: Poland
facility: Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz
city: Lublin
country: Poland
facility: Oncology Center of Lublin Land, Department of Clinical Oncology
city: Warsaw
country: Poland
facility: Institute of Hematology and Transfusion Medicine, Clinic of Hematology
city: Wroclaw
country: Poland
facility: Wroclaw Medical University, Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation
city: Brasov
country: Romania
facility: Rapid Diagnosis Polyclinic SA
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute Center for Hematology and Bone Marrow Transplantation
city: Bucharest
country: Romania
facility: Bucharest University Emergency Hospital, Hematology Clinic
city: Ekaterinburg
country: Russian Federation
facility: State Budget Healthcare Institution of Sverdlovsk region: Sverdlovsk Regional Clinical Hospital #1
city: Moscow
country: Russian Federation
facility: Federal State Public Institution: Main Military Clinical Hospital n.a. N.N. Burdenko of the Russian Ministry of Defense
city: Moscow
country: Russian Federation
facility: Moscow State Budget Medical Institution: City Clinical Hospital n.a. S.P.Botkin
city: Petrozavodsk
country: Russian Federation
facility: State Medical Institution: Republican Hospital named after V.A. Baranov
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Clinical Research and Practical Center for Specialized Types of Medical Care
city: Ufa
country: Russian Federation
facility: State Healthcare Institution: Republican Clinical Oncology Center
city: Banska Bystrica
country: Slovakia
facility: University Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Department of Hematology
city: Bratislava
country: Slovakia
facility: National Cancer Institute, Department of Hematology and Transfusiology
city: Martin
country: Slovakia
facility: University Hospital Martin, Department of Hematology and Transfusiology
city: Presov
country: Slovakia
facility: J. A. Reiman University Hospital with Polyclinic in Presov
city: A Coruña
country: Spain
facility: A Coruña University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Hebrón
city: Cadiz
country: Spain
facility: Hospital Iniversitario Puerta del Mar
city: Girona
country: Spain
facility: Institut Català de Oncologia (ICO), Hospital Dr Trueta
city: Madrid
country: Spain
facility: Hospital Iniversitario La Paz
city: Vitoria
country: Spain
facility: Hospital Universitario Araba
city: Cherkasy
country: Ukraine
facility: Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Oncology Center
city: Kyiv
country: Ukraine
facility: National Institute of Cancer
city: Lviv
country: Ukraine
facility: State Institution: Institute of Blood Pathology and Transfusion Medicine
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Center
city: London
country: United Kingdom
facility: St. George's Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: Christie Hospital, Department of Medical Oncology
Study officials:
affiliation: Sr. Director, Clinical Operations
name: Simran B Singh, MS, GWCP
role: STUDY_DIRECTOR
References:
citation: Pettengell R, Dlugosz-Danecka M, Andorsky D, Belada D, Georgiev P, Quick D, Singer JW, Singh SB, Pallis A, Egorov A, Salles G. Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306). Br J Haematol. 2020 Jan;188(2):240-248. doi: 10.1111/bjh.16255. Epub 2019 Dec 27.
citation: Belada D, Georgiev P, Dakhil S, Inhorn LF, Andorsky D, Beck JT, Quick D, Pettengell R, Daly R, Dean JP, Pavlyuk M, Failloux N, Hubel K. Pixantrone-rituximab versus gemcitabine-rituximab in relapsed/refractory aggressive non-Hodgkin lymphoma. Future Oncol. 2016 Aug;12(15):1759-68. doi: 10.2217/fon-2016-0137. Epub 2016 Apr 20.