A Study Of Inotuzumab Ozogamicin Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

AN OPEN-LABEL, RANDOMIZED, PHASE 3 STUDY OF INOTUZUMAB OZOGAMICIN ADMINISTERED IN COMBINATION WITH RITUXIMAB COMPARED TO DEFINED INVESTIGATOR'S CHOICE THERAPY IN SUBJECTS WITH RELAPSED OR REFRACTORY CD22-POSITIVE AGGRESSIVE NON-HODGKIN LYMPHOMA WHO ARE NOT CANDIDATES FOR INTENSIVE HIGH-DOSE CHEMOTHERAPY

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01232556
• Other study ID #: B1931008
• Secondary ID: 3129K5-33032010-
• Status: Terminated
• Phase: Phase 3
• Start date: April 4, 2011
• Est. completion date: March 28, 2014

Study information

• Verified date: December 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of inotuzumab ozogamicin plus rituximab in relapsed/refractory aggressive Non-Hodgkin lymphoma patients who are not candidates for intensive high-dose chemotherapy. Specifically, the goal is to demonstrate the superiority of this combination compared with an active comparator arm (investigator's choice of rituximab+bendamustine or rituximab+gemcitabine) using the primary endpoint of overall survival.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 338
• Est. completion date: March 28, 2014
• Est. primary completion date: March 28, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Exclusion Criteria:

Related Conditions & MeSH terms

• Aggression
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Inotuzumab ozogamicin
1.8 mg/m2 on day 2 every 28 days by IV infusion, 3 to 6 cycles
• Rituximab
375 mg/m2 on day 1 every 28 days by IV infusion, 3 to 6 cycles
• rituximab + gemcitabine
rituximab 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2 to 6, every 28 days by IV infusion, 3 to 6 cycles; gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days, 3 to 6 cycles
• rituximab +bendamustine
rituximab 375 mg/m2 on day 1 every 28 days by IV infusion, 3 to 6 cycles; bendamustine 120 mg/m2 on days 1 and 2 by IV infusion every 28 days, 3 to 6 cycles

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Bruxelles
Belgium	Grand Hopital de Charleroi	Charleroi
Belgium	Universitaire Ziekenhuizen Leuven	Leuven	Vlaams Brabant
Belgium	H.-Hartziekenhuis Roeselare-Menen	Roeselare
Belgium	St Augustinus Ziekenhuis	Wilrijk
Belgium	Cliniques universitaires UCL de Mont-Godinne,	Yvoir
Bulgaria	UMBAL Sveti Georgi, Klinika po hematologia	Plovdiv
Bulgaria	SBAL na Hematologichnichni Zabolyavania,CTH Sofia	Sofia
Bulgaria	Spetsializirana Bolnitsa za Aktivno Lechenie na Hematologichni Zabolyavania, CTH Sofia	Sofia
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Centre Hospitalier Universitaire de Sherbrooke (CHUS), Hopital Fleurimont	Sherbrooke	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Croatia	University Hospital Dubrava Department of Internal Medicine Division of Hematology	Zagreb
Croatia	University Hospital Zagreb	Zagreb
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10	Czech Republic
France	Hopital Andre Mignot	Le Chesnay	Yvelines
France	Hospital Universitaire Andre Mignot	Le Chesnay Cedex	Yvelines
France	Centre Leon Berard	Lyon
France	Département Pharmacie	Marseille	Bouches-du-rhône
France	Institut Paoli Calmettes	Marseille	Cedex 09
France	CHU Saint Eloi	Montpellier
France	Hopital du haut Leveque	Pessac
France	Centre Henri Becquerel	Rouen
Germany	Universitaetsklinikum Aachen	Aachen
Germany	Sozialstiftung Bamberg	Bamberg
Germany	Charite Campus Benjamin Franklin	Berlin
Germany	Charite Campus Virchow-Klinikum	Berlin
Germany	Universitaetsklinikum Mainz	Mainz
Germany	TU Muenchen III. Medizinische Klinik	Muenchen
Germany	Universitaetsklinik Ulm	Ulm
Hungary	Egyesitett Szent Istvan es Szent Laszlo Korhaz /	Budapest
Hungary	DEOEC, Belgyogyaszati Intezet	Debrechen
Hungary	Somongy Megyei Kaposi Mor Okato Korhaz/ Belgyogyaszati osztaly	Kaposvar
India	Kodlikeri Memorial Hospital	Aurangabad	Maharashtra
India	OEC Record Management Company Pvt. Ltd.,	Pune	Maharashtra
India	Sahyadri Clinical Research and Development Center	Pune	Maharashtra
India	Sahyadri Speciality Hospital	Pune	Maharashtra
Ireland	Bon Secours Hospital	Cork
Japan	Akita University Hospital	Akita
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Kyushu Cancer Center	Fukuoka
Japan	Tokai University Hospital	Kanagawa
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Cancer Institute Hospital, Japanese Foundation For Cancer Research	Koto-Ku	Tokyo
Japan	University Hospital, Kyoto Prefectural University of Medicine	Kyoto
Japan	Gunma University Hospital	Maebashi-city	Gunma
Japan	Matsushita Memorial Hospital	Moriguchi	Osaka
Japan	Nagoya Daini Red Cross Hospital	Nagoya	Aichi
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Shizuoka Cancer Center	Sunto-gun	Shizuoka
Japan	Ehime University Hospital	Toon-shi	Ehime
Lithuania	Klaipeda Seamen's Hospital, Public Institution, department of Oncology	Klaipeda
Mexico	Instituto Biomédico de Investigación A.C.	Aguascalientes	Aguascalientes. Mexico
Poland	Klinika Nowotworow Ukladu Chlonnego	Warszawa
Poland	Niepubliczny Zaklad Opieki Zdrowotnej AVI Diagnostyka Obrazowa	Warszawa
Puerto Rico	Advanced Infusion Services	Catano
Puerto Rico	Hospital Espanol Auxilio Mutuo de Puerto Rico Inc	San Juan
Russian Federation	Federal State Budgetary Institution Hematology Scientific Centre of Ministry of	Moscow
Russian Federation	Moscow State Healthcare Institution City clinical hospital S.P. Botkin	Moscow
Russian Federation	Institute of Pediatric Hematology and Transplantology R.M.Gorbacheva	Saint-Petersburg
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Slovakia	Narodny onkologicky ustav	Bratislava
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Clinic Universitari de Barcelona	Barcelona
Spain	Institut Catala d'Oncologia-L'Hospitalet	L'Hospitalet De Llobregat (bcn)
Spain	Hospital Universitario de Canarias	La Laguna (Tenerife)
Spain	Hospital de la Princesa	Madrid
Spain	Hospital Universitario De Salamanca	Salamanca	Castille AND LION
Spain	Hospital Virgen Del Rocio	Sevilla	Andalucia
Sweden	Universitetssjukhuset	Linkoping
Sweden	Skanes Universitetssjukhus i Lund	Lund
Taiwan	Chang Gung Medical Foundation - Linkou Branch	Kuei-Shan Hsiang	Taoyuan County
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital, Department of Internal Medicine	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Thailand	Hematology Division Department of Medicine Faculty of Medicine Siriraj Hospital Mahidol University	Bangkoknoi	Bangkok
Thailand	Chiang Mai University	Chiang Mai
Ukraine	Regional Treatment and Diagnostic Hematology Center Communal Establishment	Cherkasy
Ukraine	Department of Oncology and Medical Radiology of State Institution	Dnipropetrovsk
Ukraine	SI"Research Center for Radiation Medicine of NAMS of Ukraine"	Kyiv
United Kingdom	Barts Cancer Centre Dept Haemato-oncology St. Bartholomew's Hospital Barts Health NHS Trust	London
United Kingdom	Chemotherapy Preparative Unit St. Bartholomew's Hospital	London
United Kingdom	Department of Medical Oncology St. Bartholomew's Hospital	London
United Kingdom	The Christie NHS Foundation Trust - Christie Hospital	Manchester
United Kingdom	Department of Clinical Biochemistry Newcastle upon Tyne Hospitals	Newcastle upon Tyne
United Kingdom	Department of Clinical Pathology Newcastle upon Tyne Hospitals NHS Foundation Trust Royal Victoria I	Newcastle upon Tyne
United Kingdom	Northern Centre for Cancer Care	Newcastle upon Tyne
United Kingdom	Local Laboratory Nottingham University Hospital - City Hospital Campus	Nottingham
United Kingdom	Nottingham University Hospital	Nottingham
United Kingdom	Pathology Department Nottingham University Hospital - City Hospital Campus	Nottingham
United Kingdom	Pharmacy Nottingham University Hospital - City Hospital Campus	Nottingham
United Kingdom	New Cross Hospital	Wolverhampton
United States	Georgia Regents Medical Cancer Pharmacy	Augusta	Georgia
United States	Georgia Regents University	Augusta	Georgia
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	University Cancer Institute	Boynton Beach	Florida
United States	Disney Family Cancer Center at Providence St Joseph Medical Center	Burbank	California
United States	Providence St Joseph Medical Center	Burbank	California
United States	University Hospital	Cincinnati	Ohio
United States	Kootenai Cancer Center	Coeur d'Alene	Idaho
United States	Good Samaritan Hospital Corvallis	Corvallis	Oregon
United States	Good Samaritan Hospital, Corvallis	Corvallis	Oregon
United States	Samaritan Ambulatory Infusion Services	Corvallis	Oregon
United States	Baylor University Medical Center	Dallas	Texas
United States	Baylor: Charles A. Sammons Cancer Center	Dallas	Texas
United States	Simmons Comprehensive Cancer Center	Dallas	Texas
United States	University Hospital - St. Paul	Dallas	Texas
United States	University Hospital - Zale Lipshy	Dallas	Texas
United States	Decatur Memorial Hospital (DMH)	Decatur	Illinois
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Barbara Ann Karmanos Cancer Institute at farmington Hills	Farmington Hills	Michigan
United States	21st Century Oncology of Jacksonville, LLC	Fernandina Beach	Florida
United States	Hematology-Oncology Medical Group of Fresno Inc	Fresno	California
United States	Davis Cancer Pavilion and Shands Medical Plaza	Gainesville	Florida
United States	Shands Cancer Hospital at the University of Florida	Gainesville	Florida
United States	Shands Hospital at the University of Florida	Gainesville	Florida
United States	UF Health Davis Cancer Pavillion and Shands Med Plaza	Gainesville	Florida
United States	UF Health Shands Cancer Hospital	Gainesville	Florida
United States	UF Health Shands Hospital	Gainesville	Florida
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	21st Century Oncology of Jacksonville, Inc.	Jacksonville	Florida
United States	21st Century Oncology of Jacksonville, LLC	Jacksonville	Florida
United States	21st Century Oncology of Jacksonville, LLC	Jacksonville	Florida
United States	21st Century Oncology of Jacksonville, LLC	Jacksonville	Florida
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	Baptist Medical Center	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Thompson Oncology Group	Knoxville	Tennessee
United States	Thompson Oncology Group	Knoxville	Tennessee
United States	Medical Specialists Of The Palm Beaches	Lake Worth	Florida
United States	University of Kentucky A.B. Chandler Medical Center	Lexington	Kentucky
United States	University of Kentucky Markey Cancer Center	Lexington	Kentucky
United States	Southeast Nebraska Hematology & Oncology Consultants, P.C. d/b/a Southeast Nebraska Cancer Center	Lincoln	Nebraska
United States	Clinical Research Unit	Los Angeles	California
United States	Peter Morton Medical Plaza	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center Drug Information Center Department of Pharmaceutical Services	Los Angeles	California
United States	Thompson Oncology Group	Maryville	Tennessee
United States	Advanced Medical Specialties	Miami	Florida
United States	Mercy Hospital	Miami	Florida
United States	Mercy Research Institute	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Floyd Memorial Cancer Center of Indiana	New Albany	Indiana
United States	Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Beth Israel Comprehensive Cancer Center	New York	New York
United States	Beth Israel Medical Center;	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	St Luke's- Roosevelt Hospital Center	New York	New York
United States	Samaritan Pacific Coast Hospital	Newport	Oregon
United States	OU Medical Center Presbyterian Professional Building	Oklahoma City	Oklahoma
United States	OU Medical Center Presbyterian Tower	Oklahoma City	Oklahoma
United States	Peggy and Charles Stephenson Cancer Center (chemo & infusion)	Oklahoma City	Oklahoma
United States	Peggy and Charles Stephenson Cancer Center (clinic location)	Oklahoma City	Oklahoma
United States	21st Century Oncology of Jacksonville, LLC	Orange Park	Florida
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	Washington University in St Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Frauenshuh Cancer Center	Saint Louis Park	Minnesota
United States	Barnes-Jewish St. Peters	Saint Peters	Missouri
United States	Sansum Clinic	Santa Barbara	California
United States	UCLA Santa Monica Hematology Oncology	Santa Monica	California
United States	Guthrie Clinic, Ltd.	Sayre	Pennsylvania
United States	Robert Packer Hospital	Sayre	Pennsylvania
United States	Thompson Oncology Group	Sevierville	Tennessee
United States	Sansum Clinic	Solvang	California
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Stony Brook University Medical Center, The Cancer Center	Stony Brook	New York
United States	Howard University Hospital	Washington	District of Columbia
United States	West Chester Hospital Medical Building	West Chester	Ohio
United States	University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	UCB Pharma

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  Croatia,  Czechia,  France,  Germany,  Hungary,  India,  Ireland,  Japan,  Lithuania,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Singapore,  Slovakia,  Spain,  Sweden,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Overall Survival (OS) was defined as the time from randomization to death due to any cause, censoring at the date of last contact or the end of the study. The Kaplan-Meier method was used to determine OS. The hazard ratio and corresponding 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.	From randomization up to 5 years after last dose or up to final study visit, whichever occurs first.
Primary	Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population)	Includes all TEAEs: Any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration..	Up to 20 weeks after the first dose of study drug
Secondary	Progression-Free Survival (PFS)	PFS is defined as time from date of randomization to date of progressive disease (PD, including investigator's claim of clinical progression), date of death from any cause, or initiation of a new treatment for the lymphoma due to persistent/refractory disease. The Kaplan-Meier method was used to determine PFS. The hazard ratio and corresponding 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.; PD requires the following: Appearance of any new lesion more than 1.5 cm in any axis during or at the end of treatment, even if other lesions are decreasing in size.; At least a 50% increase from nadir in the sum of the product diameters of any previously involved nodes, or in a single involved node, or the size of other lesions.; At least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis.	From randomization up to 2 years or final study visit, whichever occurs first, including but not limited to planned assessments scheduled approximately every 12 weeks.
Secondary	Percentage of Participants With A Best Overall Response of CR or Partial Response (PR) Per NCI International Response Criteria for NHL	CR is defined as disappearance of all detectable clinical evidence of disease (including cleared infiltrate on repeat bone marrow aspirate/biopsy if lymphoma involvement of bone marrow before treatment).; Partial Response (PR) requires the following: =50 % decrease in SPD of the six largest dominant nodes or nodal masses.; No increase in the size of other nodes, liver, or spleen.; Splenic and hepatic nodules must regress by =50% in the SPD, or for single nodules, in the greatest transverse diameter.; With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.; No new sites of disease. The 95% CI was determined using the exact method based on binomial distribution.	Up to 2 years from first study drug dose or up to final study visit, whichever occurs first, including but not limited to planned assessments scheduled approximately every 12 weeks.
Secondary	Percentage of Participants With A Best Overall Response of CR, Unconfirmed CR (unCR), PR, or Unconfirmed PR (unPR) Per NCI International Response Criteria for NHL	CR is defined as disappearance of all detectable clinical evidence of disease (including cleared infiltrate on repeat bone marrow aspirate/biopsy if lymphoma involvement of bone marrow before treatment).; Partial Response (PR) requires the following: =50 % decrease in SPD of the six largest dominant nodes or nodal masses.; No increase in the size of other nodes, liver, or spleen.; Splenic and hepatic nodules must regress by =50% in the SPD, or for single nodules, in the greatest transverse diameter.; With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.; No new sites of disease. unCR and unPR means didn't have confirmatory assessment (including bone marrow assessment for CR).; The 95% CI was determined using the exact method based on binomial distribution.	Up to 2 years from first study drug dose or up to final study visit, whichever occurs first, including but not limited to planned assessments scheduled approximately every 12 weeks.
Secondary	Duration of Response	The duration of overall response is measured from the first date of response until the first date that the progressive disease (PD) or death is objectively documented. The hazard ratio and corresponding 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.	Up to 2 years from first study drug dose or up to final study visit, whichever occurs first, including but not limited to planned assessments scheduled approximately every 12 weeks.
Secondary	Health Status as Assessed by the European Quality of Life 5 Dimension (EQ-5D) Questionnaire	EQ-5D consists of a descriptive system and an EQ visual analogue scale. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. The scale, the best state is marked 100 and the worst state is marked 0, is to help the participant to say how good or bad a health state is. EQ-5D index, which was reported, was derived based on US weight. The range of EQ-5D index is -0.109 to 1.00. Higher scores mean better outcomes. The average post-baseline scores for EQ-5D index were computed at approximately Week 12. The overall treatment comparisons were estimated at approximately Week 12.	Assessed at Day 1 of each cycle and 6-9 weeks after the last dose, Cycle 3 (Week 12) reported
Secondary	Health Related Quality of Life as Assessed by the Functional Assessment of Cancer Therapy for Lymphoma (FACT-Lym) Questionnaire	FACT-Lym is a questionnaire that begins with 27 items covering four core Health-Related Quality of Life subscales: Physical Well-being (7 items), Social/Family Well-being (7), Emotional Well-being (6), and Functional Well-being (7). The FACT-Lym also includes an additional concerns subscale (15 items). It also asks participants about their concerns about lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. The participants were requested to circle one number on a 0 to 4 points scale per line to indicate how true each statement has been for him/her during the past 7 days. FACT-Lym total score, which was reported, was derived based on FACT-Lym scoring guideline (Version 4). The range of FACT-Lym total score is 0 to 168. Higher scores mean better outcomes. The average post-baseline FACT-Lym total scores were computed at approximately Week 12. The overall treatment comparisons were estimated at approximately Week 12.	Assessed at Day 1 of each cycle and 6-9 weeks after the last dose, Cycle 3 (Week 12) reported

External Links

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