A Study Of Inotuzumab Ozogamicin Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy
- Conditions
- Lymphoma, Non-Hodgkin
- Interventions
- Registration Number
- NCT01232556
- Lead Sponsor
- Pfizer
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 338
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 rituximab +bendamustine Investigator's choice of (1) rituximab+gemcitabine, or (2) rituximab+bendamustine 2 rituximab + gemcitabine Investigator's choice of (1) rituximab+gemcitabine, or (2) rituximab+bendamustine 1 Rituximab Inotuzumab ozogamicin+rituximab 1 Inotuzumab ozogamicin Inotuzumab ozogamicin+rituximab
- Primary Outcome Measures
Name Time Method Overall Survival From randomization up to 5 years after last dose or up to final study visit, whichever occurs first. 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.
Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) Up to 20 weeks after the first dose of study drug 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..
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) 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. 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:
1. 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.
2. 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.
3. At least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis.Percentage of Participants With A Best Overall Response of CR or Partial Response (PR) Per NCI International Response Criteria for NHL 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. 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:
1. ≥50 % decrease in SPD of the six largest dominant nodes or nodal masses.
2. No increase in the size of other nodes, liver, or spleen.
3. Splenic and hepatic nodules must regress by ≥50% in the SPD, or for single nodules, in the greatest transverse diameter.
4. With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.
5. No new sites of disease. The 95% CI was determined using the exact method based on binomial distribution.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 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. 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:
1. ≥50 % decrease in SPD of the six largest dominant nodes or nodal masses.
2. No increase in the size of other nodes, liver, or spleen.
3. Splenic and hepatic nodules must regress by ≥50% in the SPD, or for single nodules, in the greatest transverse diameter.
4. With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.
5. 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.Duration of Response 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. 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.
Health Status as Assessed by the European Quality of Life 5 Dimension (EQ-5D) Questionnaire Assessed at Day 1 of each cycle and 6-9 weeks after the last dose, Cycle 3 (Week 12) reported 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.
Health Related Quality of Life as Assessed by the Functional Assessment of Cancer Therapy for Lymphoma (FACT-Lym) Questionnaire Assessed at Day 1 of each cycle and 6-9 weeks after the last dose, Cycle 3 (Week 12) reported 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.
Related Research Topics
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Trial Locations
- Locations (168)
Ronald Reagan UCLA Medical Center Drug Information Center Department of Pharmaceutical Services
🇺🇸Los Angeles, California, United States
University of Kansas Cancer Center and Medical Pavilion
🇺🇸Westwood, Kansas, United States
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Sahyadri Clinical Research and Development Center
🇮🇳Pune, Maharashtra, India
Sahyadri Speciality Hospital
🇮🇳Pune, Maharashtra, India
Disney Family Cancer Center at Providence St Joseph Medical Center
🇺🇸Burbank, California, United States
Providence St Joseph Medical Center
🇺🇸Burbank, California, United States
Hematology-Oncology Medical Group of Fresno Inc
🇺🇸Fresno, California, United States
Peter Morton Medical Plaza
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Howard University Hospital
🇺🇸Washington, District of Columbia, United States
Sansum Clinic
🇺🇸Solvang, California, United States
UCLA Santa Monica Hematology Oncology
🇺🇸Santa Monica, California, United States
Mount Sinai Comprehensive Cancer Center at Aventura
🇺🇸Aventura, Florida, United States
University Cancer Institute
🇺🇸Boynton Beach, Florida, United States
21st Century Oncology of Jacksonville, LLC
🇺🇸Orange Park, Florida, United States
Shands Cancer Hospital at the University of Florida
🇺🇸Gainesville, Florida, United States
Davis Cancer Pavilion and Shands Medical Plaza
🇺🇸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
Shands Hospital at the University of Florida
🇺🇸Gainesville, Florida, United States
UF Health Shands Hospital
🇺🇸Gainesville, Florida, United States
Baptist Medical Center
🇺🇸Jacksonville, Florida, United States
Baptist Cancer Institute
🇺🇸Jacksonville, Florida, United States
21st Century Oncology of Jacksonville, Inc.
🇺🇸Jacksonville, Florida, United States
Medical Specialists Of The Palm Beaches
🇺🇸Lake Worth, Florida, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
Georgia Regents University
🇺🇸Augusta, Georgia, United States
Georgia Regents Medical Cancer Pharmacy
🇺🇸Augusta, Georgia, United States
Kootenai Cancer Center
🇺🇸Post Falls, Idaho, United States
Decatur Memorial Hospital (DMH)
🇺🇸Decatur, Illinois, United States
Floyd Memorial Cancer Center of Indiana
🇺🇸New Albany, Indiana, United States
University of Kentucky Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
University of Kentucky A.B. Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Tulane University Hospital and Clinic
🇺🇸New Orleans, Louisiana, United States
Park Nicollet Frauenshuh Cancer Center
🇺🇸Saint Louis Park, Minnesota, 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
Barnes-Jewish St. Peters
🇺🇸Saint Peters, Missouri, United States
Southeast Nebraska Hematology & Oncology Consultants, P.C. d/b/a Southeast Nebraska Cancer Center
🇺🇸Lincoln, Nebraska, United States
Beth Israel Medical Center;
🇺🇸New York, New York, United States
Beth Israel Comprehensive Cancer Center
🇺🇸New York, New York, United States
Stony Brook University Medical Center, The Cancer Center
🇺🇸Stony Brook, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
St Luke's- Roosevelt Hospital Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
West Chester Hospital Medical Building
🇺🇸West Chester, Ohio, United States
Good Samaritan Hospital, Corvallis
🇺🇸Corvallis, Oregon, United States
Good Samaritan Hospital Corvallis
🇺🇸Corvallis, Oregon, United States
Guthrie Clinic, Ltd.
🇺🇸Sayre, Pennsylvania, United States
Samaritan Pacific Coast Hospital
🇺🇸Newport, Oregon, United States
Samaritan Ambulatory Infusion Services
🇺🇸Corvallis, Oregon, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Robert Packer Hospital
🇺🇸Sayre, Pennsylvania, United States
University Hospital - St. Paul
🇺🇸Dallas, Texas, United States
Thompson Oncology Group
🇺🇸Sevierville, Tennessee, United States
University Hospital - Zale Lipshy
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Baylor: Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Grand Hopital de Charleroi
🇧🇪Charleroi, Belgium
Simmons Comprehensive Cancer Center
🇺🇸Dallas, Texas, United States
Universitaire Ziekenhuizen Leuven
🇧🇪Leuven, Vlaams Brabant, Belgium
H.-Hartziekenhuis Roeselare-Menen
🇧🇪Roeselare, Belgium
Spetsializirana Bolnitsa za Aktivno Lechenie na Hematologichni Zabolyavania, CTH Sofia
🇧🇬Sofia, Bulgaria
Cliniques universitaires UCL de Mont-Godinne,
🇧🇪Yvoir, Belgium
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
University Hospital Zagreb
🇭🇷Zagreb, Croatia
Centre Hospitalier Universitaire de Sherbrooke (CHUS), Hopital Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czech Republic, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Département Pharmacie
🇫🇷Marseille, Bouches-du-rhône, France
Centre Leon Berard
🇫🇷Lyon, France
Institut Paoli Calmettes
🇫🇷Marseille, Cedex 09, France
CHU Saint Eloi
🇫🇷Montpellier, France
Hopital Andre Mignot
🇫🇷Le Chesnay, Yvelines, France
Hopital du haut Leveque
🇫🇷Pessac, France
Universitaetsklinikum Aachen
🇩🇪Aachen, Germany
Sozialstiftung Bamberg
🇩🇪Bamberg, Germany
Charite Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Charite Campus Benjamin Franklin
🇩🇪Berlin, Germany
TU Muenchen III. Medizinische Klinik
🇩🇪Muenchen, Germany
Universitaetsklinik Ulm
🇩🇪Ulm, Germany
Universitaetsklinikum Mainz
🇩🇪Mainz, Germany
Egyesitett Szent Istvan es Szent Laszlo Korhaz /
🇭🇺Budapest, Hungary
DEOEC, Belgyogyaszati Intezet
🇭🇺Debrechen, Hungary
OEC Record Management Company Pvt. Ltd.,
🇮🇳Pune, Maharashtra, India
Somongy Megyei Kaposi Mor Okato Korhaz/ Belgyogyaszati osztaly
🇭🇺Kaposvar, Hungary
Kodlikeri Memorial Hospital
🇮🇳Aurangabad, Maharashtra, India
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Nagoya Daini Red Cross Hospital
🇯🇵Nagoya, Aichi, Japan
Bon Secours Hospital
🇮🇪Cork, Ireland
Akita University Hospital
🇯🇵Akita, Japan
National Kyushu Cancer Center
🇯🇵Fukuoka, Japan
University Hospital, Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Klinika Nowotworow Ukladu Chlonnego
🇵🇱Warszawa, Poland
Instituto Biomédico de Investigación A.C.
🇲🇽Aguascalientes, Aguascalientes. Mexico, Mexico
Hospital Espanol Auxilio Mutuo de Puerto Rico Inc
🇵🇷San Juan, Puerto Rico
Moscow State Healthcare Institution City clinical hospital S.P. Botkin
🇷🇺Moscow, Russian Federation
National University Hospital
🇸🇬Singapore, Singapore
Institute of Pediatric Hematology and Transplantology R.M.Gorbacheva
🇷🇺Saint-Petersburg, Russian Federation
Federal State Budgetary Institution Hematology Scientific Centre of Ministry of
🇷🇺Moscow, Russian Federation
Hospital Virgen Del Rocio
🇪🇸Sevilla, Andalucia, Spain
Narodny onkologicky ustav
🇸🇰Bratislava, Slovakia
Hospital Universitario De Salamanca
🇪🇸Salamanca, Castille AND LION, 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 Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de la Princesa
🇪🇸Madrid, Spain
Universitetssjukhuset
🇸🇪Linkoping, Sweden
Skanes Universitetssjukhus i Lund
🇸🇪Lund, Sweden
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation - Linkou Branch
🇨🇳Kuei-Shan Hsiang, Taoyuan County, Taiwan
Chiang Mai University
🇹🇭Chiang Mai, Thailand
Barts Cancer Centre Dept Haemato-oncology St. Bartholomew's Hospital Barts Health NHS Trust
🇬🇧London, United Kingdom
SI"Research Center for Radiation Medicine of NAMS of Ukraine"
🇺🇦Kyiv, Ukraine
Chemotherapy Preparative Unit St. Bartholomew's Hospital
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust - Christie Hospital
🇬🇧Manchester, United Kingdom
Department of Medical Oncology St. Bartholomew's Hospital
🇬🇧London, 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
Nottingham University Hospital
🇬🇧Nottingham, United Kingdom
Northern Centre for Cancer Care
🇬🇧Newcastle upon Tyne, United Kingdom
Pathology Department Nottingham University Hospital - City Hospital Campus
🇬🇧Nottingham, United Kingdom
Pharmacy Nottingham University Hospital - City Hospital Campus
🇬🇧Nottingham, United Kingdom
Local Laboratory Nottingham University Hospital - City Hospital Campus
🇬🇧Nottingham, United Kingdom
Mercy Research Institute
🇺🇸Miami, Florida, United States
Advanced Medical Specialties
🇺🇸Miami, Florida, United States
Mercy Hospital
🇺🇸Miami, Florida, United States
University Hospital
🇺🇸Cincinnati, Ohio, United States
Hematology Division Department of Medicine Faculty of Medicine Siriraj Hospital Mahidol University
🇹🇭Bangkoknoi, Bangkok, Thailand
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Centre Henri Becquerel
🇫🇷Rouen, France
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, 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
Clinical Research Unit
🇺🇸Los Angeles, California, United States
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
University Hospital Dubrava Department of Internal Medicine Division of Hematology
🇭🇷Zagreb, Croatia
Tohoku University Hospital
🇯🇵Sendai, Miyagi, Japan
Matsushita Memorial Hospital
🇯🇵Moriguchi, Osaka, Japan
Tokai University Hospital
🇯🇵Kanagawa, Japan
Klaipeda Seamen's Hospital, Public Institution, department of Oncology
🇱🇹Klaipeda, Lithuania
Regional Treatment and Diagnostic Hematology Center Communal Establishment
🇺🇦Cherkasy, Ukraine
SBAL na Hematologichnichni Zabolyavania,CTH Sofia
🇧🇬Sofia, Bulgaria
National Taiwan University Hospital, Department of Internal Medicine
🇨🇳Taipei, Taiwan
Shizuoka Cancer Center
🇯🇵Sunto-gun, Shizuoka, Japan
St Augustinus Ziekenhuis
🇧🇪Wilrijk, Belgium
Ehime University Hospital
🇯🇵Toon-shi, Ehime, Japan
Advanced Infusion Services
🇵🇷Catano, Puerto Rico
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Hospital Universitaire Andre Mignot
🇫🇷Le Chesnay Cedex, Yvelines, France
Niepubliczny Zaklad Opieki Zdrowotnej AVI Diagnostyka Obrazowa
🇵🇱Warszawa, Poland
Singapore General Hospital
🇸🇬Singapore, Singapore
UMBAL Sveti Georgi, Klinika po hematologia
🇧🇬Plovdiv, Bulgaria
Gunma University Hospital
🇯🇵Maebashi-city, Gunma, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Cancer Institute Hospital, Japanese Foundation For Cancer Research
🇯🇵Koto-Ku, Tokyo, Japan
Department of Oncology and Medical Radiology of State Institution
🇺🇦Dnipropetrovsk, Ukraine
Barbara Ann Karmanos Cancer Institute at farmington Hills
🇺🇸Farmington Hills, Michigan, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States