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

Diffuse Large B-cell Lymphoma Clinical Trial

— PIX-R  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01321541
• Other study ID #: PIX306 (PIX-R Trial)
• Status: Completed
• Phase: Phase 3
• Start date: April 20, 2011
• Est. completion date: September 14, 2018

Study information

• Verified date: September 2021
• Source: CTI BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 312
• Est. completion date: September 14, 2018
• Est. primary completion date: June 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aggression
• de Novo DLBCL
• Diffuse Large B-cell Lymphoma
• DLBCL Transformed From Indolent Lymphoma
• Follicular Grade 3 Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Pixantrone + Rituximab
Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
• Gemcitabine + Rituximab
Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.

Locations

Country	Name	City	State
Austria	Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology)	Innsbruck
Austria	Hospital Elisabethinen Linz, Internal Department 1 - Hemato-Oncology	Linz
Austria	Hanusch Hospital, Department of Internal Medicine III	Vienna
Belgium	Saint Luc University Hospital, Department of Hematology	Brussels
Belgium	General Hospital Delta, Hematology Department	Roeselare
Belgium	General Hospital Turnhout, Hematology Department	Turnhout
Bulgaria	UMHAT "Sveti Georgi", Plovdiv, Clinical Hematology Clinic	Plovdiv
Bulgaria	UMHAT "Sveti Georgi", Plovdiv, Department of Medical Oncology	Plovdiv
Bulgaria	MHAT "Tokuda Hospital Sofia", Hematology Clinic	Sofia
Bulgaria	Specialized Hospital For Active Treatment Of Hematological Diseases, Sofia, Clinical Hematology Clinic	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Department of Clinical Hematology	Sofia
Bulgaria	MHAT Hristo Botev, Vratsa, First Department of Internal Medicine	Vratsa
Czechia	University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology	Brno
Czechia	University Hospital Hradec Kralove, 4th Department of Internal Medicne, Clinical Hematology	Hradec Kralove
Czechia	University Hospital Ostrava, Institute of Clinical Hematology	Ostrava
Czechia	General University Hospital in Prague, 1st Department of Internal Medicine - Department of Hematology	Prague
Czechia	University Hospital Kralovske Vinohrady, Department of Clinical Hematology	Prague
Denmark	Aalborg University Hospital, Department of Hematology	Aalborg
France	Service d'hématologie clinique, Avenue Laennec Salouel	Amiens, Cedex 1
France	Centre hopitalier de la cote basque	Bayonne
France	Centre hospitalier de Beziers	Beziers
France	Polyclinique de Bordeaux nord Acquitaine	Bordeaux
France	Centre hospitalier du Mans	Le Mans Cedex 03
France	Centre hospitalier Lyon Sud	Pierre Benite Cedex
France	Saint Quentin Hospital Center, Department of Oncology-Hematology	Saint-Quentin
France	Hautepierre Hospital, Department of Hematology and Oncology	Strasbourg Cedex
Germany	Gemeinschaftspraxis Drs. Klausmann	Aschaffenburg
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Klinik für Innere Medizin III	Frankfurt (a.M.)
Germany	Universitaetsklinikum Halle	Halle (Saale)
Germany	St. Marien Hospital Hamm	Hamm
Germany	Universitätsklinik Köln	Köln
Germany	Klinikum Nürnberg Nord	Nürnberg
Germany	Klinikum Mutterhaus der Borromäerinnen	Trier
Hungary	St. Istvan and St. Laszlo Hospital of Budapest	Budapest
Hungary	University of Debrecen	Debrecen
Hungary	Moritz Kaposi General Hospital	Kaposvár
Italy	University Hospital "Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi"	Ancona
Italy	Bologna University Hospital Authority St. Orsola-Malpighi Polyclinic	Bologna
Italy	Scientific Institute of Romagna for the Study and Treatment of Cancer (I.R.S.T.) S.R.L.	Meldola
Italy	"Ospedali Riuniti Villa Sofia-Cervello" Hospital	Palermo
Italy	Romagna Local Health Authority (AUSL Romagna) - "Santa Maria delle Croci"	Ravenna
Italy	Romagna Local Health Authority (AUSL Romagna) - "Infermi" Hospital	Rimini
Italy	Siena University Hospital Authority Santa Maria alle Scotte Polyclinic	Siena
Italy	Santa Maria Hospital	Terni
Italy	A.O.U. Città della Salute e della Scienza di Torino	Torino
Poland	Independent Public Healthcare Facility Municipal Hospital Group	Chorzów
Poland	Marine Hospital of Polish Red Cross, Department of Chemotheraphy	Gdynia
Poland	Silesia Medical University, Department of Hematology and Bone Marrow Transplantation	Katowice
Poland	Malopolskie Medical Center S.C. , Department of Hematology	Krakow
Poland	Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz	Lodz
Poland	Oncology Center of Lublin Land, Department of Clinical Oncology	Lublin
Poland	Institute of Hematology and Transfusion Medicine, Clinic of Hematology	Warsaw
Poland	Wroclaw Medical University, Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation	Wroclaw
Romania	Rapid Diagnosis Polyclinic SA	Brasov
Romania	Bucharest University Emergency Hospital, Hematology Clinic	Bucharest
Romania	Fundeni Clinical Institute Center for Hematology and Bone Marrow Transplantation	Bucharest
Russian Federation	State Budget Healthcare Institution of Sverdlovsk region: Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	Federal State Public Institution: Main Military Clinical Hospital n.a. N.N. Burdenko of the Russian Ministry of Defense	Moscow
Russian Federation	Moscow State Budget Medical Institution: City Clinical Hospital n.a. S.P.Botkin	Moscow
Russian Federation	State Medical Institution: Republican Hospital named after V.A. Baranov	Petrozavodsk
Russian Federation	St. Petersburg Clinical Research and Practical Center for Specialized Types of Medical Care	St. Petersburg
Russian Federation	State Healthcare Institution: Republican Clinical Oncology Center	Ufa
Slovakia	University Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Department of Hematology	Banska Bystrica
Slovakia	National Cancer Institute, Department of Hematology and Transfusiology	Bratislava
Slovakia	University Hospital Martin, Department of Hematology and Transfusiology	Martin
Slovakia	J. A. Reiman University Hospital with Polyclinic in Presov	Presov
Spain	A Coruña University Hospital	A Coruña
Spain	Hospital Universitario Vall Hebrón	Barcelona
Spain	Hospital Iniversitario Puerta del Mar	Cadiz
Spain	Institut Català de Oncologia (ICO), Hospital Dr Trueta	Girona
Spain	Hospital Iniversitario La Paz	Madrid
Spain	Hospital Universitario Araba	Vitoria
Ukraine	Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center	Cherkasy
Ukraine	Kharkiv Regional Clinical Oncology Center	Kharkiv
Ukraine	National Institute of Cancer	Kyiv
Ukraine	State Institution: Institute of Blood Pathology and Transfusion Medicine	Lviv
United Kingdom	Beatson West of Scotland Cancer Center	Glasgow
United Kingdom	St. George's Healthcare NHS Trust	London
United Kingdom	Christie Hospital, Department of Medical Oncology	Manchester
United States	Rocky Mountain Cancer Centers	Aurora	Colorado
United States	Harry and Jeanette Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland
United States	Highlands Oncology Group	Bentonville	Arkansas
United States	Center for Cancer and Blood Disorders, PC	Bethesda	Maryland
United States	Rocky Mountain Cancer Centers	Boulder	Colorado
United States	Gabrail Cancer Center	Canton	Ohio
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Carle Physician Group	Danville	Illinois
United States	Cancer Care Specialists of Central Illinois	Decatur	Illinois
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Gabrail Cancer Center	Dover	Ohio
United States	North Shore Hematology/Oncology Associates	East Setauket	New York
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Metro Minnesota CCOP-Unity Hospital	Fridley	Minnesota
United States	Cancer & Hematology Center of Western Michigan	Grand Rapids	Michigan
United States	Green Bay Oncology-St. Mary's Hospital MC	Green Bay	Wisconsin
United States	Saint Vincent Hospital Green Bay Oncology	Green Bay	Wisconsin
United States	Upstate Oncology Associates	Greenville	South Carolina
United States	South Carolina Cancer Specialists	Hardeeville	South Carolina
United States	South Carolina Cancer Specialists	Hilton Head Island	South Carolina
United States	Integrated Community Oncology Network-Southside	Jacksonville	Florida
United States	Integrated Community Oncology Network-St. Vincent's	Jacksonville	Florida
United States	Nebraska Hematology-Oncology, PC	Lincoln	Nebraska
United States	Baptist Hospital East	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Metro Minnesota CCOP-St. Johns	Maplewood	Minnesota
United States	Carle Foundation Physician Services	Mattoon	Illinois
United States	Hematology-Oncology Associates of Northern New Jersey	Morristown	New Jersey
United States	Cancer Care Centers of South Texas-HOAST	New Braunfels	Texas
United States	Integrated Community Oncology Network	Orange Park	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Northwest Cancer Specialists, PC	Portland	Oregon
United States	Northwest Cancer Specialists, PC	Portland	Oregon
United States	Blue Ridge Cancer Care	Roanoke	Virginia
United States	Metro Minnesota Community Clinical Oncology Program	Saint Louis Park	Minnesota
United States	Metro Minnesota Community Clinical Oncology Program	Saint Louis Park	Minnesota
United States	Metro Minnesota CCOP-Regions Hospital	Saint Paul	Minnesota
United States	Cancer Care Centers of South Texas-HOAST	San Antonio	Texas
United States	Mercy Cancer Center at St. Anne's	Toledo	Ohio
United States	Toledo Clinic Cancer Center-Toledo	Toledo	Ohio
United States	Toledo Clinical Cancer Center	Toledo	Ohio
United States	Northwest Cancer Specialists, PC	Tualatin	Oregon
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	Northwest Cancer Specialists, PC	Vancouver	Washington
United States	Northwest Cancer Specialists, PC	Vancouver	Washington
United States	George Washington University Department of Medicine	Washington	District of Columbia
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
CTI BioPharma

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  Czechia,  Denmark,  France,  Germany,  Hungary,  Italy,  Poland,  Romania,  Russian Federation,  Slovakia,  Spain,  Ukraine,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Individual Concentration-time Profiles of Patients Will be Compared to Existing Data Using Simulations (Visual Predictive Checks)	To characterize the PK profile of pixantrone when co-administered with rituximab. Plasma samples for PK analysis will be collected relative to the D-1 dose of pixantrone in one of the 6 treatment cycles for each participating patient. The goal is to enroll approx. 20 patients, active at 20 sites- Beatson West of Scotland Cancer Center, Uni. Hospital Kralovske Vinohrady, Uni. Hospital Hradec Kralove Hematooncology, Hospital Nuernberg, St. Marien Hospital Hamm, Puerta del Mar Hospital, Tokuda Hospital Sofia, National Center of Hematology & Transfusiology, UMHAT "SV. IVAN RILSKI", Moritz Kaposi General Hospital, Uni. of Debrecen, Polish Red Cross Marine Hospital, Kharkiv Regional Clinical Oncology Center, National Inst. of Cancer Ukraine, Cherkasy Regional Oncology Center, Inst. of Blood Pathology & Transfusion Medicine, Uni. Hospital Martin, National Onclogy Inst., Uni. Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Uni. Hospital J.A. Reiman Presov	within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion
Other	To Generate Individual Secondary PK Parameters (eg, Exposure, Half-life Etc.) Using Descriptive Statistics	To characterize the PK profile of pixantrone when co-administered with rituximab. Plasma samples for PK analysis will be collected relative to the D-1 dose of pixantrone in one of the 6 treatment cycles for each participating patient. The goal is to enroll approx. 20 patients, active at 20 sites- Beatson West of Scotland Cancer Center, Uni. Hospital Kralovske Vinohrady, Uni. Hospital Hradec Kralove Hematooncology, Hospital Nuernberg, St. Marien Hospital Hamm, Puerta del Mar Hospital, Tokuda Hospital Sofia, National Center of Hematology & Transfusiology, UMHAT "SV. IVAN RILSKI", Moritz Kaposi General Hospital, Uni. of Debrecen, Polish Red Cross Marine Hospital, Kharkiv Regional Clinical Oncology Center, National Inst. of Cancer Ukraine, Cherkasy Regional Oncology Center, Inst. of Blood Pathology & Transfusion Medicine, Uni. Hospital Martin, National Onclogy Inst., Uni. Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Uni. Hospital J.A. Reiman Presov	within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion
Primary	Progression Free Survival (PFS)	PFS is defined as the time of randomization to the date of disease progression or death due to any cause (whichever occurs first)	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	Overall Survival	Overall survival is from randomization to death due to any cause	From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)
Secondary	Complete Response Rate	CRR is defined as the proportion of patients who achieve a Complete Response (CR) without additional therapy. CR is defined as the disappearance of all target lesions.	From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)
Secondary	Overall Response Rate	ORR is defined as the proportion of patients who achieve a CR or PR without additional therapy.	From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)
Secondary	Number of Treatment Emergent Adverse Events (TEAE) Related to Study Drug	The number of Participants with Treatment Emergent Adverse Events (TEAE) related to study drug (pixantrone or gemcitabine)	From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)

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