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A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab

4 marzo 2020 aggiornato da: 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).

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

190

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre
  • Francia
      • RENNES cedex 9, Francia, 35033
        • Centre d'investigation Clinique
  • Giappone
      • Akita, Giappone, 010-8543
        • Akita University Hospital
      • Tokyo, Giappone, 135-8550
        • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
    • Chiba
      • Kashiwa, Chiba, Giappone, 277-8577
        • National Cancer Center Hospital East
  • Italia
    • BO
      • Bologna, BO, Italia, 40138
        • Az. Ospedaliera-Univer. di Bologna Policlinico S. Orsola Malpighi
    • MI
      • Milano, MI, Italia, 20132
        • Ospedale San Raffaele di Milano
  • Stati Uniti
    • California
      • Duarte, California, Stati Uniti, 91010
        • City of Hope
      • La Jolla, California, Stati Uniti, 92093
        • UC San Diego Moores Cancer Center
      • La Jolla, California, Stati Uniti, 92037-0845
        • UC San Diego Moores Cancer Center-Investigational Drug Services
      • La Jolla, California, Stati Uniti, 92037
        • UC San Diego Medical Center-La Jolla (Jacobs Medical Center/Thornton Hospital)
      • Los Angeles, California, Stati Uniti, 90095
        • Ronald Reagan UCLA Medical Center, Drug Information Center
      • Los Angeles, California, Stati Uniti, 90095
        • UCLA Hematology-Oncology Clinic
      • Los Angeles, California, Stati Uniti, 90095
        • Research Administration Office: Clinical Research Unit
      • Los Angeles, California, Stati Uniti, 90095
        • UCLA Bowyer Clinic
      • Palo Alto, California, Stati Uniti, 94304
        • Stanford University Medical Center
      • Palo Alto, California, Stati Uniti, 94305
        • Stanford University Medical Center
      • San Diego, California, Stati Uniti, 92103
        • UC San Diego Medical Center - Hillcrest
      • Santa Monica, California, Stati Uniti, 90404
        • Santa Monica UCLA Hematology & Oncology Clinic
      • Stanford, California, Stati Uniti, 94305
        • Stanford University Medical Center
    • District of Columbia
      • Washington, District of Columbia, Stati Uniti, 20007
        • MedStar Georgetown University Hospital
      • Washington, District of Columbia, Stati Uniti, 20007
        • Georgetown University Medical Center Department of Pharmacy, Research
    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30322
        • Emory University Hospital
      • Atlanta, Georgia, Stati Uniti, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, Stati Uniti, 30322
        • The Emory Clinic
      • Atlanta, Georgia, Stati Uniti, 30322
        • Winship Cancer Institute
      • Atlanta, Georgia, Stati Uniti, 30322
        • The Emory Clinic, Building A
    • Massachusetts
      • Boston, Massachusetts, Stati Uniti, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, Stati Uniti, 02115
        • Brigham and Woman's Hospital
    • Michigan
      • Ann Arbor, Michigan, Stati Uniti, 48109
        • University of Michigan Health System
    • Missouri
      • Creve Coeur, Missouri, Stati Uniti, 63141
        • Siteman Cancer Center-West County
      • Saint Louis, Missouri, Stati Uniti, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, Stati Uniti, 63110
        • Barnes-Jewish Hospital
      • Saint Louis, Missouri, Stati Uniti, 63110
        • Washington University Infusion Center Pharmacy
      • Saint Louis, Missouri, Stati Uniti, 63110-1094
        • Barnes-Jewish Hospital
      • Saint Louis, Missouri, Stati Uniti, 63129
        • Siteman Cancer Center- South County
      • Saint Peters, Missouri, Stati Uniti, 63376
        • Siteman Cancer Center - St. Peters
    • New York
      • New York, New York, Stati Uniti, 10065
        • Memorial Sloan Kettering Cancer Center
    • Texas
      • Houston, Texas, Stati Uniti, 77030
        • The University of Texas - M.D. Anderson Cancer Center
      • San Antonio, Texas, Stati Uniti, 78229
        • South Texas Accelerated Research Therapeutics, LLC
    • Washington
      • Seattle, Washington, Stati Uniti, 98109
        • Seattle Cancer Care Alliance
      • Seattle, Washington, Stati Uniti, 98195
        • University of Washington Medical Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Portion A
PF-05082566 single agent in patients with advanced cancer
Droga: PF-05082566
Intravenous, Dose escalation, once per month
Droga: PF-05082566
IV, Dose escalation, once per month
Sperimentale: Portion B
PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
Droga: PF-05082566
Intravenous, Dose escalation, once per month
Droga: PF-05082566
IV, Dose escalation, once per month
Droga: rituximab
Intravenous, 375 mg/m2, once per week for 4 weeks
Altri nomi:
  • Rituxan, MabThera

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A
Lasso di tempo: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
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.
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
Number of Participants With DLTs in First 2 Cycles of Portion B
Lasso di tempo: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
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.
Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A
Lasso di tempo: Up to approximately 2 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 2 years
Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A
Lasso di tempo: Up to approximately 2 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 2 years
Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A
Lasso di tempo: 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 A
Lasso di tempo: 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.
Up to approximately 2 years
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A
Lasso di tempo: Up to approximately 2 years
For vital signs in Portion A, blood pressure and pulse rate were measured. Clinical significance was determined by the investigator.
Up to approximately 2 years
PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A
Lasso di tempo: 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
Cmax of PF-05082566 was observed directly from data.
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
PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A
Lasso di tempo: Day 1 pre-dose of Cycle 2
Ctrough of PF-05082566 was observed directly from data.
Day 1 pre-dose of Cycle 2
PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A
Lasso di tempo: 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.
Tmax of PF-05082566 was observed directly from data as time of Cmax.
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.
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
Lasso di tempo: 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.
AUClast of PF-05082566 was determined by linear/log trapezoidal method.
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.
PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A
Lasso di tempo: 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.
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.
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.
PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A
Lasso di tempo: 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.
AUCtau of PF-05082566 was determined using linear/log trapezoidal method.
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.
PF-05082566 Clearance (CL) in Portion A
Lasso di tempo: 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.
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).
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.
PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A
Lasso di tempo: 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.
Vss = CL × MRT, where CL is clearance and MRT is the mean residence time after intravenous administration.
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.
Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A
Lasso di tempo: Up to approximately 2 years
ADA for PF-05082566 was detected using electrochemiluminescence assay. Positive ADA for PF-05082566: titer>=6.23.
Up to approximately 2 years
Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A
Lasso di tempo: Up to approximately 2 years
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.
Up to approximately 2 years
Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A
Lasso di tempo: 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: 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.
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 A
Lasso di tempo: 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: 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.
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 A
Lasso di tempo: 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: 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.
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 A
Lasso di tempo: 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: 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.
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 A
Lasso di tempo: 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)
Number of Participants With Treatment-Emergent AEs and SAEs in Portion B
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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.
Up to approximately 2 years
Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B
Lasso di tempo: 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.
Up to approximately 2 years
PF-05082566 Cmax in Portion B
Lasso di tempo: 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.
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.
PF-05082566 Ctrough in Portion B
Lasso di tempo: Day 1 pre-dose of Cycle 2
Ctrough of PF-05082566 was observed directly from data.
Day 1 pre-dose of Cycle 2
PF-05082566 Tmax in Portion B
Lasso di tempo: 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.
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.
PF-05082566 AUClast in Portion B
Lasso di tempo: 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.
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.
PF-05082566 AUCinf in Portion B
Lasso di tempo: 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.
Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.
PF-05082566 AUCtau in Portion B
Lasso di tempo: 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.
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
Lasso di tempo: 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.
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
Lasso di tempo: 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
Lasso di tempo: Day 1 pre-dose of Cycle 2
Cmax and Ctrough of rituximab were observed directly from data.
Day 1 pre-dose of Cycle 2
Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Biomarkers Linked With Immunomodulation and Cytokine Release
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Pfizer

Pubblicazioni e link utili

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Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

21 giugno 2011

Completamento primario (Effettivo)

20 febbraio 2019

Completamento dello studio (Effettivo)

20 febbraio 2019

Date di iscrizione allo studio

Primo inviato

28 febbraio 2011

Primo inviato che soddisfa i criteri di controllo qualità

28 febbraio 2011

Primo Inserito (Stima)

2 marzo 2011

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

17 marzo 2020

Ultimo aggiornamento inviato che soddisfa i criteri QC

4 marzo 2020

Ultimo verificato

1 marzo 2020

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • B1641001
  • 2011-002799-17 (Numero EudraCT)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Descrizione del piano IPD

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.

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su Linfoma, follicolare

Prove cliniche su PF-05082566

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Guinea

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

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