Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator's Choice In Follicular Non-Hodgkin's Lymphoma (NHL)
- Conditions
- Lymphoma, Follicular
- Interventions
- Registration Number
- NCT00562965
- Lead Sponsor
- Pfizer
- Brief Summary
This protocol is designed to assess the efficacy and safety of inotuzumab ozogamicin given with rituximab compared to a defined investigator's choice therapy. Subjects will be randomized to one of these two arms of the study.
- Detailed Description
On January 14th 2009, enrollment in the study was discontinued because of poor enrollment and because it was unlikely that the study would meet the estimated enrollment of approximately 978 subjects. The decision was not prompted by the identification of any safety signals in this or other studies. Active treatment and follow-up of the already enrolled subjects was continued. On July, 22th 2010 , the study was amended to shorten the long-term follow-up to one year after active treatment.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 29
- Subjects with a diagnosis of CD20 and CD22-positive, follicular lymphoma, who have received 1 or 2 prior regimens, at least 1 of which should have contained administration of rituximab (either as a single agent or in combination).
- Age 18 years or older.
- ECOG performance status <= 2.
- ANC >= 1.5 x 10^9/L (1500/mL) and platelets >= 75 x 10^9/L (75,000/mL), serum creatinine <= 1.5 x ULN and urine protein to creatinine ratio of <= 0.5, total bilirubin <= 1.5 x ULN, AST and ALT <= 2.5 x ULN.
- At least 1 measurable disease lesion that is >= 1.5 cm x 1.5 cm by CT or MRI, in an area of no prior radiation therapy, or documented progression in an area that was previously irradiated.
- Subjects with clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b follicular lymphoma.
- Subjects whose disease is rituximab refractory, meaning that they did not have a CR or PR, or that they experienced disease progression within 6 months from the initiation of the rituximab or rituximab containing treatment regimen administered immediately preceding study enrollment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A rituximab Subjects will receive rituximab intravenously at a dose level of 375 mg/m² on day 1 of each cycle followed by inotuzumab ozogamicin administered intravenously at a dose level of 1.8 mg/m2 on day 2. The sequence will be repeated every 28 days. B prednisone/prednisolone Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5. B mitoxantrone Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5. A inotuzumab ozogamicin Subjects will receive rituximab intravenously at a dose level of 375 mg/m² on day 1 of each cycle followed by inotuzumab ozogamicin administered intravenously at a dose level of 1.8 mg/m2 on day 2. The sequence will be repeated every 28 days. B rituximab Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5. B cyclophosphamide Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5. B vincristine Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5. B fludarabine Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5. B dexamethasone Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Baseline until disease progression or death or up to 1 year after last dose of study drug PFS was defined as the time from randomization to disease progression or death due to any cause, whichever occurred first, censored at the last tumor evaluation date. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.44.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics of Inotuzumab Ozogamicin in Combination With Rituximab 0, 1, 168 hours on Cycle 1, 2; 0, 1, 2, 168 hours on Cycle 3, 4 Percentage of Participants With Objective Response (OR) Baseline, every 6 to 12 weeks during treatment period, end of treatment (EOT) (42 days after last dose), every 12 weeks during follow-up for up to 1 year after the last dose of study drug OR was based on assessment of complete response(CR),unconfirmed CR(Cru),partial response(PR) as per International Response Criteria for Non-Hodgkin's Lymphoma.Confirmed response=response persists on repeat imaging at least 4 weeks after initial response.CR=complete disappearance of all detectable clinical/radiographic evidence of disease,lymph nodes regressed to normal size \[at least 1.5 centimeter(cm) or less\],spleen regressed,not palpable on physical examination,bone marrow infiltrate cleared on repeat aspiration/biopsy.PR=at least 50 percent (%) decrease in sum of product diameters of 6 greatest dominant nodes,no increase in other nodes,liver/spleen,no new sites of disease. CRu=residual lymph node greater than 1.5 cm in transverse diameter that has regressed more than 75% in product diameter.Individual nodes previously confluent,regressed more than 75% in product diameters.Indeterminate bone marrow (increased number/size of lymph aggregates without cytologic/architectural atypia).
Overall Survival Probability at Months 6, 12 and 24 Baseline up to Month 6, 12, 24 Overall survival 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. Participants who withdrew or lost to follow-up from study without having death documented were censored at the date of last contact. Kaplan-Meier estimates of the probability of survival at 6, 12 and 24 months was used to estimate the survival function.
Trial Locations
- Locations (37)
Wenatchee Valley Medical Center
🇺🇸Wenatchee, Washington, United States
Park Nicollet Frauenshuh Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
Facey Medical Group
🇺🇸Mission Hills, California, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Avi Einzing, MD
🇺🇸Bronx, New York, United States
Deaconess Clinic
🇺🇸Evansville, Indiana, United States
Newland Medical Associates, PC
🇺🇸Southfield, Michigan, United States
Hematology and Oncology Associates
🇺🇸Corinth, Mississippi, United States
Yonsei University Health System-Severance Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Universitario de Nuevo Leon
🇲🇽Monterrey, Nuevo LEON, Mexico
The Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
CHUS-Hopital Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
Advanced Oncology Associates
🇺🇸New Rochelle, New York, United States
Moscow Regional Research Clinical Institute named after Vladimirsky
🇷🇺Moscow, Russian Federation
Newland Medical Associates
🇺🇸Novi, Michigan, United States
Instytut Hematologii i Transfuzjologii
🇵🇱Warszawa, Poland
Hospital de La Princesa
🇪🇸Madrid, Spain
Divisione di Ematologia - Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
MMF Joshi Hospital and Ratna Memorial Hospital
🇮🇳Pune, Maharashtra, India
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Oncologisch Centrum GZA - Location St. Augustinus
🇧🇪Wilrijk, Belgium
Jehangir Clinical Development Centre
🇮🇳Pune, Maharashtra, India
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
C.H.A. Enfant-Jesus
🇨🇦Quebec, Canada
Hospitais Da Universidade De Coimbra
🇵🇹Coimbra, Portugal
Wits Donald Gordon Clinical Trial Site
🇿🇦Johannesburg, Gauteng, South Africa
B. P. Poddar Hospital and Medical Research Ltd.
🇮🇳Kolkata, WEST Bengal, India
Hematology Oncology Associates of Northern New Jersy
🇺🇸Morristown, New Jersey, United States
The Harry & Jeanette Weinberg Cancer Inst at Franklin Square
🇺🇸Baltimore, Maryland, United States
Hematology and Oncology Associates at Bridgepoint
🇺🇸Tupelo, Mississippi, United States
Marc Zimmerman, MD
🇺🇸Pomona, New York, United States
Centro de Transplantes de medula Osea de Rosario, CETRAMOR
🇦🇷Rosario, Santa FE, Argentina
Hopital Charles LeMoyne
🇨🇦Greenfield Park, Quebec, Canada
Prince of Wales Hospital
🇭🇰Shatin, NEW Territories, Hong Kong
Hospital Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong