- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01307267
A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab
4 mars 2020 uppdaterad av: Pfizer
A PHASE 1 STUDY OF PF-05082566 AS A SINGLE AGENT IN PATIENTS WITH ADVANCED CANCER, AND IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA (NHL)
A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Faktisk)
190
Fas
- Fas 1
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Victoria
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Melbourne, Victoria, Australien, 3000
- Peter MacCallum Cancer Centre
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RENNES cedex 9, Frankrike, 35033
- Centre d'Investigation Clinique
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California
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Duarte, California, Förenta staterna, 91010
- City of Hope
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La Jolla, California, Förenta staterna, 92093
- UC San Diego Moores Cancer Center
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La Jolla, California, Förenta staterna, 92037-0845
- UC San Diego Moores Cancer Center-Investigational Drug Services
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La Jolla, California, Förenta staterna, 92037
- UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)
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Los Angeles, California, Förenta staterna, 90095
- Ronald Reagan UCLA Medical Center, Drug Information Center
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Los Angeles, California, Förenta staterna, 90095
- UCLA Hematology-Oncology Clinic
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Los Angeles, California, Förenta staterna, 90095
- Research Administration Office: Clinical Research Unit
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Los Angeles, California, Förenta staterna, 90095
- UCLA Bowyer Clinic
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Palo Alto, California, Förenta staterna, 94304
- Stanford University Medical Center
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Palo Alto, California, Förenta staterna, 94305
- Stanford University Medical Center
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San Diego, California, Förenta staterna, 92103
- UC San Diego Medical Center - Hillcrest
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Santa Monica, California, Förenta staterna, 90404
- Santa Monica UCLA Hematology & Oncology Clinic
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Stanford, California, Förenta staterna, 94305
- Stanford University Medical Center
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District of Columbia
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Washington, District of Columbia, Förenta staterna, 20007
- MedStar Georgetown University Hospital
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Washington, District of Columbia, Förenta staterna, 20007
- Georgetown University Medical Center Department of Pharmacy, Research
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Georgia
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Atlanta, Georgia, Förenta staterna, 30322
- Emory University Hospital
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Atlanta, Georgia, Förenta staterna, 30308
- Emory University Hospital Midtown
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Atlanta, Georgia, Förenta staterna, 30322
- The Emory Clinic
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Atlanta, Georgia, Förenta staterna, 30322
- Winship Cancer Institute
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Atlanta, Georgia, Förenta staterna, 30322
- The Emory Clinic, Building A
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Massachusetts
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Boston, Massachusetts, Förenta staterna, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Förenta staterna, 02115
- Brigham and Woman's Hospital
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Michigan
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Ann Arbor, Michigan, Förenta staterna, 48109
- University of Michigan Health System
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Missouri
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Creve Coeur, Missouri, Förenta staterna, 63141
- Siteman Cancer Center-West County
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Saint Louis, Missouri, Förenta staterna, 63110
- Washington University School of Medicine
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Saint Louis, Missouri, Förenta staterna, 63110
- Barnes-Jewish Hospital
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Saint Louis, Missouri, Förenta staterna, 63110
- Washington University Infusion Center Pharmacy
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Saint Louis, Missouri, Förenta staterna, 63110-1094
- Barnes-Jewish Hospital
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Saint Louis, Missouri, Förenta staterna, 63129
- Siteman Cancer Center- South County
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Saint Peters, Missouri, Förenta staterna, 63376
- Siteman Cancer Center - St. Peters
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New York
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New York, New York, Förenta staterna, 10065
- Memorial Sloan Kettering Cancer Center
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Texas
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Houston, Texas, Förenta staterna, 77030
- The University of Texas - M.D. Anderson Cancer Center
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San Antonio, Texas, Förenta staterna, 78229
- South Texas Accelerated Research Therapeutics, LLC
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Washington
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Seattle, Washington, Förenta staterna, 98109
- Seattle Cancer Care Alliance
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Seattle, Washington, Förenta staterna, 98195
- University of Washington Medical Center
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BO
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Bologna, BO, Italien, 40138
- Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi
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MI
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Milano, MI, Italien, 20132
- Ospedale San Raffaele di Milano
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Akita, Japan, 010-8543
- Akita University Hospital
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Tokyo, Japan, 135-8550
- The Cancer Institute Hospital of Japanese Foundation for Cancer Research
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Chiba
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Kashiwa, Chiba, Japan, 277-8577
- National Cancer Center Hospital East
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria
- Portion A: Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy or B cell lymphoma, for which no curative therapy is available. Portion A expansion includes patients who have documented disease progression on a checkpoint inhibitor (anti CTLA 4, anti PD1/PD L1 antibodies) per RECIST criteria. Tumor types include metastatic melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NCSLC) and squamous cell carcinoma of the head and neck (SCCHN). Patients in the dose expansion stage are required to provide archival or baseline (obtained during the screening period) tumor biopsies.
- Portion B: Histological confirmed relapsed or refractory CD20 positive NHL for which no curative therapy is available. Patients enrolled in the expansion cohort must have archival tissue available, sampled within 6 months of study entry. The Expansion cohort includes patients with FL or DLBCL with relapsed or refractory disease.
- Measurable disease with at least one extranodal tumor mass >1.0 cm in the greatest transverse diameter (GTD) or in the case of malignant lymph nodes >1.5 cm in the GTD.
- ECOG performance status of ≤ 1.
- Adequate bone marrow function, for Portion A: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥100 x 109/L, hemoglobin >9.0 g/dL. For Portion B: ANC ≥ 1.0 x 109/L, platelet count ≥ 75 x 109/L, and hemoglobin ≥ 8.0 g/dL. In both cases, patients must be transfusion independent at least 14 days prior to screening.
- Serum creatinine ≤ 2 x ULN or estimated creatinine clearance ≥ 50 ml/min.
- Total serum bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert syndrome and AST and ALT ≤ 2.5 x ULN.
Exclusion Criteria
- Patients with known symptomatic brain metastases requiring steroids.
- Prior allogeneic hematopoietic stem cell transplant.
- Immunosuppressive regimens involving systemic corticosteroids within 14 days before the first dose of study treatment.
- Therapeutic or experimental monoclonal antibodies within 28 day or prior radiation therapy within 14 days of the first dose of study drug.
- Autoimmune disorders and other diseases that compromise or impair the immune system.
- Unstable or serious concurrent medical conditions in the previous 6 months.
- Prior therapy with any anti CD137 monoclonal antibody.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: Portion A
PF-05082566 single agent in patients with advanced cancer
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Intravenous, Dose escalation, once per month
IV, Dose escalation, once per month
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Experimentell: Portion B
PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
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Intravenous, Dose escalation, once per month
IV, Dose escalation, once per month
Intravenous, 375 mg/m2, once per week for 4 weeks
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A
Tidsram: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
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DLT: Any of the following adverse events (AEs) occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 alone for Portion A and not related to progressive disease.
Hematologic: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis.
Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT).
Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Each cycle=28 days.
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Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
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Number of Participants With DLTs in First 2 Cycles of Portion B
Tidsram: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
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DLT: Any of the following AEs occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 in combination with rituximab for Portion B and not related to progressive disease.
Hematologic: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis.
Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT).
Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
Each cycle=28 days.
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Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A
Tidsram: Up to approximately 2 years
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
AEs included both non-serious AEs and SAEs.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Causality of AEs was determined by the investigator.
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Up to approximately 2 years
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Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A
Tidsram: Up to approximately 2 years
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
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Up to approximately 2 years
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Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Tidsram: Up to approximately 2 years
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Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells.
The abnormalities with at least 1 participant are presented here.
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Up to approximately 2 years
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Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Tidsram: Up to approximately 2 years
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Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.
The abnormalities with at least 1 participant are presented here.
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Up to approximately 2 years
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Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A
Tidsram: Up to approximately 2 years
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For vital signs in Portion A, blood pressure and pulse rate were measured.
Clinical significance was determined by the investigator.
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Up to approximately 2 years
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PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A
Tidsram: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose
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Cmax of PF-05082566 was observed directly from data.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose
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PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A
Tidsram: Day 1 pre-dose of Cycle 2
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Ctrough of PF-05082566 was observed directly from data.
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Day 1 pre-dose of Cycle 2
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PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A
Tidsram: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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Tmax of PF-05082566 was observed directly from data as time of Cmax.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 Area Under the Serum Concentration-Time Profile (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUClast) in Portion A
Tidsram: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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AUClast of PF-05082566 was determined by linear/log trapezoidal method.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A
Tidsram: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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AUCinf = AUClast + (Clast*/kel), where Clast* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A
Tidsram: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 Clearance (CL) in Portion A
Tidsram: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2. It was reported in units of milliliter per hour per kilogram (mL/hr/kg).
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A
Tidsram: Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
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Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.
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Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A
Tidsram: Up to approximately 2 years
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ADA for PF-05082566 was detected using electrochemiluminescence assay.
Positive ADA for PF-05082566: titer>=6.23.
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Up to approximately 2 years
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Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A
Tidsram: Up to approximately 2 years
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Categorical summarization criteria for QTc interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole corrected for heart rate): 1) absolute value of >450 to <=480 milliseconds (msec), >480 to <=500 msec, >500 msec; 2) a maximum change from baseline of >30 to <=60 msec or >60 msec.
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Up to approximately 2 years
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Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Objective response: confirmed best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST version 1.1.
BOR of CR: target lesions and non-target diseases achieved CR, without new lesions.
BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-progression of disease (non-PD), indeterminate or missing, and without new lesions.
For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Duration of Response in Portion A
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Duration of response: the time from first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1) to the date of first documentation of objective progression of disease (PD) or death due to any cause.
Objective PD per RECIST version 1.1: >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 millimeters (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
This outcome measure reports the individual values for evaluable participants (instead of medians etc) due to the limited number of events.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Time to Response in Portion A
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Time to response: the time from Cycle 1 Day 1 to the first documentation of objective response (confirmed BOR of CR or PR per RECIST version 1.1).
BOR of CR: target lesions and non-target diseases achieved CR, without new lesions.
BOR of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-PD, indeterminate or missing, and without new lesions.
For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes decreased to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions.
For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Progression-Free Survival in Portion A
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Progression-free survival: the time from Cycle 1 Day 1 to the date of the first documentation of objective PD or death due to any cause, whichever occurred first.
Objective PD per RECIST version 1.1: >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm; or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Overall Survival in Portion A
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
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Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
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Number of Participants With Treatment-Emergent AEs and SAEs in Portion B
Tidsram: Up to approximately 4 years
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
AEs included both non-serious AEs and SAEs.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Causality of AEs was determined by the investigator.
|
Up to approximately 4 years
|
Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B
Tidsram: Up to approximately 4 years
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Severity of AEs were graded according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE).
|
Up to approximately 4 years
|
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Tidsram: Up to approximately 2 years
|
Following hematology laboratory abnormalities were graded per NCI CTCAE version 4.03: anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils (absolute), platelets, white blood cells.
The abnormalities with at least 1 participant are presented here.
|
Up to approximately 2 years
|
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B
Tidsram: Up to approximately 2 years
|
Following chemistries laboratory abnormalities were graded per NCI CTCAE version 4.03: alanine aminotransferase (ALT), Alkaline phosphatase, Aspartate aminotransferase (AST), bilirubin (total), creatinine, gamma glutamyl transferase (GGT), hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.
The abnormalities with at least 1 participant are presented here.
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Up to approximately 2 years
|
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B
Tidsram: Up to approximately 2 years
|
For vital signs in Portion B, blood pressure, pulse rate, and body temperature were measured.
Clinical significance was determined by the investigator.
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Up to approximately 2 years
|
PF-05082566 Cmax in Portion B
Tidsram: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
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Cmax of PF-05082566 was observed directly from data.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
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PF-05082566 Ctrough in Portion B
Tidsram: Day 1 pre-dose of Cycle 2
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Ctrough of PF-05082566 was observed directly from data.
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Day 1 pre-dose of Cycle 2
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PF-05082566 Tmax in Portion B
Tidsram: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
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Tmax of PF-05082566 was observed directly from data as time of Cmax.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
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PF-05082566 AUClast in Portion B
Tidsram: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
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AUClast of PF-05082566 was determined by linear/log trapezoidal method.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
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PF-05082566 AUCinf in Portion B
Tidsram: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
|
AUCinf = AUClast + (Clast*/kel), where Clast* is the estimated concentration at the time of the last measurable concentration and kel is the terminal phase rate constant calculated as the absolute value of the slope of a linear regression during the terminal phase of the natural log-transformed concentration time profile.
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Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
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PF-05082566 AUCtau in Portion B
Tidsram: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
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AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
PF-05082566 CL in Portion B
Tidsram: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
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CL = Dose/AUCinf for Cycle 1 and Dose/AUCtau for Cycle 2.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
PF-05082566 Vss in Portion B
Tidsram: Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
|
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.
|
Rituximab Cmax and Ctrough in Portion B
Tidsram: Day 1 pre-dose of Cycle 2
|
Cmax and Ctrough of rituximab were observed directly from data.
|
Day 1 pre-dose of Cycle 2
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Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B
Tidsram: Up to approximately 2 years
|
ADA for PF-05082566 and rituximab was detected using electrochemiluminescence assay.
Positive ADA for PF-05082566: titer>=6.23.
Positive ADA for rituximab: titer>=1.88.
|
Up to approximately 2 years
|
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B
Tidsram: Up to approximately 2 years
|
Categorical summarization criteria for QTc interval: 1) absolute value of >450 to <=480 milliseconds (msec), >480 to <=500 msec, >500 msec; 2) a maximum change from baseline of >30 to <=60 msec or >60 msec.
|
Up to approximately 2 years
|
Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Objective Response in Portion B was defined as BOR of CR or PR according to Cheson 2007 criteria.
BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or >=50% decrease in the sum of the product diameters [SPD] of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion >=15 mm in greatest transverse diameter [GTD], unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Duration of Response in Portion B
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Duration of Response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from first documentation of objective response to the date of first documentation of objective PD or death due to any cause.
Objective PD per Cheson 2007 was defined as: PD of index lesions (>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Time to Response in Portion B
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Time to response in Portion B was defined, for participants with an objective response (BOR of CR or PR per Cheson 2007 criteria), as the time from Cycle 1 Day 1 to the first documentation of objective response.
BOR of CR or PR per Cheson 2007: CR or PR of index lesions (complete disappearance of all detectable clinical and radiographic evidence of disease, all lymph nodes returned to normal size, spleen and/or liver if enlarged prior to therapy became normal or no longer palpable; or >=50% decrease in the SPD of up to 6 index lesions, no increase in size of other nodes, liver or spleen), without PD of non-index lesions (ie, without: new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), and without any new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Progression-Free Survival in Portion B
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Progression-free survival in Portion B was defined as the time from Cycle 1 Day 1 to the date of the first documentation of objective PD (per Cheson 2007) or death due to any cause, whichever occurred first.
Objective PD per Cheson 2007 was defined as: PD of index lesions (>=50% increase in SPD of previously involved sites from nadir), or PD of non-index lesions (new nonnodal lesion, new nodal lesion >=15 mm in GTD, unequivocal progression of existing non index lesions, bone marrow that was negative and is now positive, new circulating lymphoma cells in blood cell count and/or pleural fluid, new circulating blasts in the blood cell count), or appearance of new lesions.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Overall Survival in Portion B
Tidsram: Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Overall survival was defined as the time from Cycle 1 Day 1 to the date of death due to any cause.
|
Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years)
|
Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Biomarkers Linked With Immunomodulation and Cytokine Release
Tidsram: Days 1, 14, 29 and 57
|
This was an exploratory endpoint and no data were collected.
|
Days 1, 14, 29 and 57
|
Exploratory Pharmacodynamic Biomarkers
Tidsram: Days 1 and 21
|
This was an exploratory endpoint and no data were collected.
|
Days 1 and 21
|
Patient-Reported Outcomes of PF-05082566 and Rituximab When Given in Combination in Follicular Lymphoma Participants
Tidsram: Up to 2 years
|
This was an exploratory endpoint and was not evaluated.
Patient-reported outcome questionnaires were not completed as a result of administrative processing error.
|
Up to 2 years
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- Gopal AK, Levy R, Houot R, Patel SP, Popplewell L, Jacobson C, Mu XJ, Deng S, Ching KA, Chen Y, Davis CB, Huang B, Fly KD, Thall A, Woolfson A, Bartlett NL. First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas. Clin Cancer Res. 2020 Jun 1;26(11):2524-2534. doi: 10.1158/1078-0432.CCR-19-2973. Epub 2020 Mar 6.
- Segal NH, He AR, Doi T, Levy R, Bhatia S, Pishvaian MJ, Cesari R, Chen Y, Davis CB, Huang B, Thall AD, Gopal AK. Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer. Clin Cancer Res. 2018 Apr 15;24(8):1816-1823. doi: 10.1158/1078-0432.CCR-17-1922. Epub 2018 Mar 16.
Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
21 juni 2011
Primärt slutförande (Faktisk)
20 februari 2019
Avslutad studie (Faktisk)
20 februari 2019
Studieregistreringsdatum
Först inskickad
28 februari 2011
Först inskickad som uppfyllde QC-kriterierna
28 februari 2011
Första postat (Uppskatta)
2 mars 2011
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
17 mars 2020
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
4 mars 2020
Senast verifierad
1 mars 2020
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Luftvägssjukdomar
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Lymfoproliferativa störningar
- Lymfatiska sjukdomar
- Immunproliferativa störningar
- Lungsjukdomar
- Urologiska neoplasmer
- Urogenitala neoplasmer
- Neoplasmer efter plats
- Njursjukdomar
- Urologiska sjukdomar
- Adenocarcinom
- Neoplasmer, körtel och epitel
- Neoplasmer i andningsvägarna
- Thoracic neoplasmer
- Karcinom, bronkogent
- Bronkiella neoplasmer
- Neoplasmer i huvud och hals
- Neuroektodermala tumörer
- Neoplasmer, könsceller och embryonala
- Neoplasmer, nervvävnad
- Neoplasmer i njurarna
- Lungneoplasmer
- Neuroendokrina tumörer
- Nevi och melanom
- Neoplasmer, skivepitelceller
- Lymfom, B-cell
- Lymfom
- Lymfom, follikulärt
- Lymfom, stor B-cell, diffus
- Karcinom, njurcell
- Karcinom, icke-småcellig lunga
- Carcinom
- Lymfom, icke-Hodgkin
- Melanom
- Karcinom, skivepitel
- Skivepitelcancer i huvud och hals
- Läkemedels fysiologiska effekter
- Antireumatiska medel
- Antineoplastiska medel
- Immunologiska faktorer
- Antineoplastiska medel, immunologiska
- Rituximab
- Antikroppar, monoklonala
- Immunoglobulin G
Andra studie-ID-nummer
- B1641001
- 2011-002799-17 (EudraCT-nummer)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
NEJ
IPD-planbeskrivning
Pfizer will provide access to individual de-identified participant data and related study documents (e.g.
protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.
Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på PF-05082566
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M.D. Anderson Cancer CenterPfizer; ISA Pharmaceuticals B.V.AvslutadOrofaryngeal cancer | Maligna neoplasmer av dåligt definierade sekundära och ospecificerade platser | Maligna neoplasmer i munhålan och svalget i läpparnaFörenta staterna
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PfizerAvslutadNeoplasmerFörenta staterna, Nederländerna, Frankrike, Japan
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PfizerAvslutadAvancerad cancerFörenta staterna, Kanada, Storbritannien, Taiwan, Australien, Frankrike, Japan, Polen
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PfizerMerck Sharp & Dohme LLCAvslutadAvancerade solida tumörerFörenta staterna
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Aktiv, inte rekryterandeMalign fast neoplasma | Avancerad malignt fast neoplasma | Eldfast malignt fast neoplasma | Kastrationsresistent prostatakarcinom | Metastaserande prostatakarcinom | Steg IV prostatacancer AJCC v8 | Metastatisk malign fast neoplasma | Steg IVA prostatacancer AJCC v8 | Steg IVB prostatacancer AJCC v8 | Prostatakarcinom...Förenta staterna
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Hope Rugo, MDJohns Hopkins University; Pfizer; Gilead Sciences; Hoosier Cancer Research... och andra samarbetspartnersRekryteringSteg IV Bröstcancer | Återkommande bröstkarcinom | Steg IIIA Bröstcancer | Steg IIIB Bröstcancer | Invasivt bröstkarcinom | Ooperabelt bröstkarcinom | Steg IIIC Bröstcancer | Trippelnegativt bröstkarcinom | Steg III BröstcancerFörenta staterna
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William Beaumont HospitalsAvslutadBlodförlust, kirurgiskt | Intraoperativa komplikationer | Komplikationer; Artroplastik | AxelledssjukdomFörenta staterna
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Aktiv, inte rekryterandeMetastaserande kolorektalt karcinom | Steg IV kolorektal cancer AJCC v8 | Steg IVA kolorektal cancer AJCC v8 | Steg IVB kolorektal cancer AJCC v8 | Steg IVC kolorektal cancer AJCC v8Förenta staterna
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George W. Sledge Jr.National Cancer Institute (NCI)AvslutadSteg IV Bröstcancer | Återkommande bröstkarcinom | Steg IIIA Bröstcancer | Steg IIIB Bröstcancer | Steg IIIC Bröstcancer | HER2 Positivt bröstkarcinom | Steg III BröstcancerFörenta staterna